Page 503«..10 20..502503504 505..510 520..»

Category Archives: Transhuman News

Do Animals Understand What It Means to Die? – VICE

Posted: February 5, 2022 at 5:07 am

In the summer of 2018, a baby albino chimpanzee was spotted in the Budongo Forest Reserve in Uganda, the first to be seen in the wild. With his white fur and pale skin, the chimpanzee provoked an immediate rousing in the rest of the group. Other chimps made alarm calls and waa barks, noises that usually signal an encounter with a potentially dangerous animal.

On July 19, adult chimpanzees killed the baby. It was a tragic incident, recalled Susana Mons, a philosopher at the Universidad Nacional de Educacin a Distancia in Madrid and the author of Schrdinger's Possum. But what she found most striking was how the chimps behaved after the baby had died.

Though the primates had exhibited fear calls when the albino was alive, once he died, they stopped. Then they readily approached him, inspected his fur and body, and groomed his back.

For Mons, who has been studying whether animals have a concept of death, this incident provides a clue that animals have some notion that death means, at the very least, he's not going to move anymore.

When they first saw the baby, they expected something scary to happen, she said. Then, at the moment it died, they weren't scared by it at all. This means their expectations have shifted.

We know that animals often behave in particular ways toward dead members of their own species. Ravens and crows gather and make loud calling noises. Chimpanzees in the Ta Forest in Africa have been seen covering dead bodies with leafy branches. In 2015, when a wild female chimpanzee died, the male she had been in a relationship with for three and a half years prevented young individuals from approaching her while he performed several close-contact and caretaking behaviors. Some primate mothers carry the body of their dead infant for days or weeks, or eat parts of the mummified corpse. Elephants have been seen gathering around, interacting with, or carrying the bodies of their babies. Dolphins sometimes keep dead bodies afloat, and in 2011 a beluga whale mother carried her dead calf for around a week.

A field called comparative thanatology documents these practices, and compares how different species interact with death and the dying. Hanging over this research are more philosophical questions: What do these behaviors really mean? Are animals acting in instinctive, hormonal, and unaware ways? Or, when they interact with their dead, do they have some level of understanding of the concept of death?

When interpreting animal behavior, there's always the risk of anthropomorphism, or projecting human-like emotions and thoughts onto nonhuman animals. But there could still be ways to probe whether animals have a concept of death with philosophy's help, by defining what a concept of death is at a bare minimum, and combining observations of animals in the wild with experiments in the lab.

Learning whether animals can grasp such concepts will help us to better understand their minds, and it could have important implications for the ways we treat them. But grappling with the concept of death is a trait long considered to belong to humans alone. Showing that animals can grasp it tooeven on a smaller scalewould mean were not alone in engaging with our mortality.

There is nothing more human than being anguished by deathor asking, as Leo Tolstoy did, Is there any meaning in my life that wouldnt be destroyed by the death that inevitably awaits me?

But from the ancient world to the Enlightenment and onward, philosophers and scientists have had mixed views on whether we share this trait with nonhuman animals, since having a concept of death is tied up with larger questions around animal consciousness.

Aristotle thought that humans were different from other animals because we have a rational soul, whereas animals had sensitive souls, which could respond to sensory impressions but not have the capacity for rational thought. Ren Descartes was less generous: He believed that animals were just mechanisms or automata, not much different than a complex cuckoo clock. There is none that leads weak minds further from the straight path of virtue than that of imagining that the souls of beasts are of the same nature as our own, he wrote.

Watch more from VICE:

Italian philosopher Giambattista Vico wrote that a human custom that separates humans from animals is burial of the dead, Baron de Montesquieu wrote animals can suffer from death but dont know what it is, and Arthur Schopenhauer claimed animals live in the present and only "know" of death when it happens to them, while humans reminisce about the past and anticipate the future with the knowledge of their own mortality. As Jean-Jacques Rousseau wrote, An animal will never know what it is to die, and the knowledge of death and its terrors is one of the first acquisitions that man has made in moving away from the animal condition.

The list goes on into the 20th century with philosophers such as Martin Heidegger, anthropologists like Ernest Becker, or biologists like Theodosius Dobzhansky making similar claims, said Andr Gonalves, a researcher at the Primate Research Institute at Kyoto University in Inuyama, Japan. The history of how animals respond to death is a long one, albeit scattered and mostly confined to footnotes, from Aristotle to Darwin to the present.

This history likely influenced those who later observed animals responding to death. For most of the 20th century, behaviors like dead-infant carrying were viewed as animals not being able to tell the difference between the living and the dead, and not worth investigating. Monkeys and apes do not recognize death, for they react to their companions as if the latter were alive but passive, wrote the primatologist Solly Zuckerman in 1932.

Because of this view, there was little attention paid to what animals did with their dead until 2010, when a publication described the death of an elder female chimpanzee. Humans observed pre-death care of the chimpanzee, other chimps testing for signs of life at the moment of death, the female chimpanzees adult daughter staying by her all night, her corpse being cleaned, and, later, the place where she died being avoided.

Without death-related symbols or rituals, chimpanzees show several behaviors that recall human responses to the death of a close relative, wrote professor of psychology James Anderson and his colleagues at Kyoto University. Are humans uniquely aware of mortality? We propose that chimpanzees awareness of death has been underestimated.

For the past 15 years, the field of comparative thanatology has taken up this investigation in earnest. (In Greek mythology, Thanatos was the personification of death.) It has focused on cataloging exactly how animals respond to death, and comparing between species, and being open to the idea that these responses arent just automata.

A paper from 2019 described how humans removed a dead infant bonnet macaque from its mother, who then regularly visited its burial spot for at least two days. Chimpanzees have been observed in whats called stunned silence, when their usual calling noises stop after the death of a chimp.

After the death of the adult female chimp that Anderson observed, he wrote, The next day, the three surviving chimpanzees were profoundly subdued. From the day area they watched silently as two keepers lowered Pansy from the platform, carried her into the exit corridor, placed her in a body bag, and loaded her into a vehicle that was then driven away. They remained subdued the following day as the night area was cleaned.

Many agree that great apes and also monkeys show compassionate care for the dying, but whether they have an understanding of death is uncertain. Plenty of thanatologists have instead come to the opposite conclusion: that the animals they observe do not have a concept of death. As Charles Darwin wondered in The Descent of Man, Who can say what cows feel, when they surround and stare intently on a dying or dead companion?

I hold a semi-agnostic position in relation to other species having a concept of death, Gonalves said. Nonhuman social animals are not always wholly indifferent to death; they have reactions and perform all sorts of behaviors surrounding it, and I think these merits further investigation.

Understanding the concept of death is different from being able to classify or distinguish the dead from the living. Ants perform necrophoresis, which is when they remove dead ants from their nestsmeaning they can tell which ones are dead and which are alive. What the ants are detecting is not the concept of death but a chemical called oleic acid that dead ants produce. Its been shown that if you put oleic acid on any object in the nest, other ants will remove it.

Other animals have similar discrimination skills, which are not a conceptual understanding. This is where philosophy can provide guidance, according to Mons. To ask whether animals have a concept of death, it first requires defining what a minimal concept of death would beor what are the minimum requirements an animal would need to meet for us to conclude they know what it is.

Humans have a complex concept of death, weighed down by cultural baggage and myriad emotional responses. This is part of why many academics may not believe that animals can understand the concept of death, said Jennifer Vonk, a comparative psychologist at Oakland University. There hasnt been much evidence that nonhuman animals can represent abstract, unobservable constructs.

But just like when we try to assess whether animals possess some sort of language or communication skill, we dont start by asking whether they can write sonnets. We break language down into its fundamental parts and ask if animals have a cognitive grasp on those first.

Mons started with building blocks of death that come from developmental psychology studies where human children are interviewed about death. Those subcomponents of death are: non-functionality, irreversibility, universality, personal mortality, inevitability, causality, and unpredictability. Some elements, like inevitability and personal mortality, are certainly part of a humans concept of death, but Mons argued that the essence of a rudimentary concept of death doesnt need to include them. At its core, Mons proposed, just non-functionality and irreversibility are fundamental. This would mean that an animal understands that death makes an individual not functional, and that its non-functioning is permanent.

Proposing a definition for exactly what a minimal concept of death is from a philosophical perspective could help those who do comparative thanatology be specific about what theyre looking for, she said. Mons thinks its likely that this bare minimum could be achieved in many species. After all, death is common in nature, and there could be evolutionary advantages to understanding what it means to die, or to know another is dead.

But this is far from agreed upon. In a paper from last year on the behavior of animal mothers toward the body of their dead offspring, research scientist Arianna de Marco and her co-authors pushed back against the animals having a concept of death per se, instead suggesting that animals like great apes can understand something more vague: that something serious has happened.

They wrote that a great ape could understand that another animal has entered a state of dormancy, or is unlikely to regain wakefulness. Recognizing that another animal is dormant and wont wake up can still elicit a powerful emotional response or behavior.

However, there is no evidence that any nonhuman primates are aware of mortality, they wrote.

Gonalves and Vonk agreed that non-functionality and irreversibility are important components of the human concepts of death, and also that the concept of death is likely a continuum, with nonhuman animals finding themselves somewhere along it. But just because death is everywhere doesnt mean its necessarily an advantage for animals to recognize it. In fact, humans recognition of their own mortality has led to psychological coping strategies, called Terror Management Theory.

Nonhumans may recognize when an individual is no longer a functioning agent interacting with the world, but I would be surprised if they appreciated an end of consciousness or mental life in the same way that adult humans do, or if they recognize that all living beings die and that death is irreversible, Vonk said. That does not mean that they do not have a concept of death; it simply means that their concept of death may be more limited and less abstract than the human concept.

If a mother chimp finally leaves her babys body behind, does that mean she understands irreversibility? If a group of elephants leaves their dead behind, does it mean they understand that it is dead forever and wont be coming back? Or is it just that theyre frustrated and giving up?

Like chimpanzees, elephants will often return to the corpse; how do we interpret this? Gonalves said. Do they realize their group member is dead? Were they just passing by and happened on it by chance? Are they paying respects, not unlike humans do in funerals? Are they checking in to see if their group member recovered? While I'm more inclined to believe the last explanation, the truth is we can only guess what's going on in their minds.

Outside of guessing, there are ways to try to test for a minimal concept of death. One is by observational studies: watching what animals do in response to the dead and making interpretations. The other is in the lab: setting up experiments that test how they either respond to the dead, or looking for cognitive abilities that might imply that could understand the concept of deathlike the ability to recognize non-functionality and irreversibility.

Some studies like this have been done before. In 1973, an experiment showed mother squirrel monkeys with the dead bodies of their own and other infants. The mothers who had offspring that had died at an older age reacted more to the corpses. One study from 1964 tested the reaction of Rhesus monkeys to fear-provoking stimuli, including live snakes; an awake and alive monkey of their species; an anesthetized monkey; and a dead monkey that had been decapitated, holding its head in its hands. The results were unclear: The decapitated monkey did get more looks than the live one, but the overall looking time was higher for the live monkey. Since the study design didn't allow touching either the dead or alive monkey, its hard to make sense of it. There are obvious ethical dilemmas around such experiments, and Mons said she wouldn't encourage such studies being done today.

Instead, Mons proposed testing animals for being able to understand non-functionality and irreversibility through stand-ins like tools or machines that break irreversibility. One such study has just started using Goffins cockatoos at the University of Veterinary Medicine in Vienna, said Alice Auersperg, a cognitive biologist who heads the cockatoo lab.

They are highly intelligent and have strong social bonds between individuals that can last for multiple years or even decades, Auersperg said. Moreover, they are able to use several types of tools which are very rare in animals yet important for our test setups. In recent work, they showed that the cockatoos could use composite tools in an experimental setup inspired by the game of golf. The experiments wont test for the concept of death directly but rather for the cognitive capacities that Mons theorized are necessary to understand death.

Not everyone is convinced that this kind of study can tell us much about death. David Pea-Guzmn, a philosopher at San Francisco State University, agreed that non-invasive studies should be done, but he doesnt think that animals would respond to machine or tool stand-ins in the same way as other animals.

Animals dont develop emotional attachments to the machines they are exposed to in a laboratory; they dont incorporate them into their social dynamics or care economy; neither do they treat them as purposive social agents, he said. In short, animals are not confused about the difference between the [mechanical] and the living.

Mons agreed that something needs to be alive before you can conceive of it to be dead, so a tool doesnt fall into that category. But if combined with observational evidence of animals in the wild, it could make for a compelling case.

Even if we're not talking about living functions, we are still in the neighborhood of the cognition you would need for the concept of death, Mons said.

Mons believes that an outright assumption that animals cant have even a minimum concept of death at all is a byproduct of anthropocentrism, or the centering of human thoughts and feelings and experience. She thinks theres been too much of a focus on grief as a reaction to death, and that it clouds our interpretation of animals behavior.

When the research chimpanzee Washoes baby died, its body was removed. Washoe then signed to a researcher, Baby? The researcher signed back, Baby dead, baby gone, baby finished. According to the researcher, Washoe dropped her cradled arms to her lap. She moved over to a far corner and looked away, her eyes vacant.

Its hard not to project feelings onto a scene like this. For humans, death is often paired with grief, and grief is distracting. Additionally, a fear of death and dying has led humans to ruminate on complex metaphysical themes, said Pea-Guzmn, like the directionality of time, the immortality of the soul, and reincarnation.

Because of this, we tend to assume that only creatures who engage in such fancy philosophizing possess a death concept, Pea-Guzmn said. It is almost as if in thinking about death we automatically conjure up an image of a dejected human pondering the meaning of life, as in Vesaliuss sketch of a human skeleton gazing at a skull in De humani corporis fabrica.

Pea-Guzmn agreed that researchers should try to look for the core of the concept of death, since the concept as we know it could include components that make sense to us as humans but are not essential.

If we are interested in animals relationship to death as a topic on its own, and not only in relation to humans, we have to also look way beyond practices that we can identify with. One example is when pets feed on their owners after they die. This is an extremely common phenomenon, much more common than we want it to be, Mons said. Even with dogs, who have strong bonds with their owners, weve seen examples of dogs eating their owners 45 minutes after the owner died and with food in their bowl.

Mons said the pattern of eating is also different than when a dog would be scavenging; when dogs scavenge, they usually eat the abdomen area first, but in these cases dogs focus on the face. Its a very disturbing behavior, but I think it's a super interesting one, Mons said. But it's only discussed in forensic science papers. I think one of the reasons may be why it hasn't been deemed relevant until now has to do with the fact that it's not a behavior that we can really relate to.

Gonalves doesnt agree that comparative thanatologists are conflating grief with the concept of death. In 2013, Barbara King wrote in her book How Animals Grieve that grief does not presuppose a concept of death and has been reiterated many times since, Gonalves said. He said we shouldnt look away from interesting phenomena out of a fear for anthropomorphism either, just as we shouldnt ignore behaviors that dont look or feel like grief to us.

Still, Gonalves has seen articles that describe animals as having mourning rituals and understanding death (and said the Wikipedia page on animal grief is absolutely dreadful), and he thinks there's reason to be careful.

There's no evidence currently that they do have anything that counts as a ritual, he said. If you ask any researcher dedicated towards the study of cultural aspects in nonhuman animals, I don't think you'll find any saying they do have so-called mourning rituals.

Gonalves advocated for field researchers using cameras to more objectively record entire interactions around death, and then making interpretations after the fact. Vonk and Georgia State University psychologist Sarah Brosnan, have proposed that a data repository be created where all responses to death could be recorded, and in 2020 anthropologist Alecia Carter created the ThanatoBase, where researchers can add their observations on primate death.

While Gonalves doesnt agree with many of Monss claims, he does think she explored more thoroughly the question of the concept of death in nonhuman animals than anyone that came before, and in doing so has perhaps uncovered a need for more careful delineations into what should count or not as good evidence for said concept.

What if animals do know what it means to die? Does it change the way we should treat them? It might shift some of our responsibilities with the animals under our care. For instance, we could ask what are the cases when we should allow them to learn about death, and when we should give them an opportunity to understand what happens when another animal has died.

Perhaps we have an ethical obligation to at least prevent animals in factory farms and laboratories from seeing or hearing other animals being killed, seeing dead bodies lying around, or experiencing markers of death, Pea-Guzmn said.

Mons also thinks we should allow animals their full reactions without interference. I think that monkey mothers who want to cling to their babies should be allowed to do so for as long as they need, she said. This might conflict with the interest of a zoo, for instance, because it might be disturbing for the visitors to see the mother holding onto a decomposing corpse. But I think that the interests of the monkey should be weighed here.

For the pets in our homes, it could mean we have a moral duty to show up for animals when they experience death, to help them mourn when they are bereaved and to be at their side to reassure them when their own time has come, Pea-Guzmn said.

Ben Bradley, a philosopher at Syracuse University, said there have been some philosophers who argue that the concept of death is necessary in order for death to be bad for you. As long as an animals life is painless, killing them is no harm since they dont know what death means.

If you cant conceptualize something, then you cant care about it, and so it cant be bad for you, he explained. If this is right, then if animals dont have a concept of death, their deaths arent bad for them. This would have important implications for how we treat animals, because it would imply that it is morally permissible to kill them for food, unless it were wrong for some reason other than being bad for the animals.

Bradley thinks we should reject the claim that nothing can be bad for you unless you care about it. He wrote a book chapter on this called Death Is Bad for a Cow, and also a song of the same name, with the lyrics:

Listen to me and I will tell you how

When you take that cow to the butcher's knife

You deprive the cow of the goods the goods of her future life

Don't need to have a sense of self over time

Or know what it means to reach the end of the line

Death is a serious harm

Even if, even if you live on a farm.

Gonalves said we shouldnt wait until the concept of death is proven to try to treat animals in ethical ways. We should prevent the infliction of unnecessary pain and suffering regardless of them having a concept of death or not, Gonalves said.

On a larger level, Mons sees this work, and question, as continuing to chip away at the idea of human cognitive superiority over animals in all domains. Whenever we can prove that there is continuity in a particular aspect of our mental lives in the mental lives of other animals, she said, it undermines any claims of human superiority that we use to justify our boundless exploitation of nature.

Follow Shayla Love onTwitter.

More:
Do Animals Understand What It Means to Die? - VICE

Posted in Immortality Medicine | Comments Off

Buxus and Tetracentron genomes help resolve eudicot genome history – Nature.com

Posted: February 3, 2022 at 4:16 pm

Govaerts, R. How many species of seed plants are there? TAXON 50, 10851090 (2001).

Google Scholar

Friis, E. M., Pedersen, K. R. & Crane, P. R. Cretaceous angiosperm flowers: Innovation and evolution in plant reproduction. Palaeogeogr., Palaeoclimatol., Palaeoecol. 232, 251293 (2006).

Google Scholar

Magalln, S., Gmez-Acevedo, S., Snchez-Reyes, L. L. & Hernndez-Hernndez, T. A metacalibrated time-tree documents the early rise of flowering plant phylogenetic diversity. N. Phytol. 207, 437453 (2015).

Google Scholar

Jiao, Y. et al. Ancestral polyploidy in seed plants and angiosperms. Nature 473, 97100 (2011).

ADS CAS PubMed Google Scholar

Amborella Genome Project. The Amborella genome and the evolution of flowering plants. Science 342, 1241089 (2013).

Google Scholar

Schranz, M. E., Mohammadin, S. & Edger, P. P. Ancient whole genome duplications, novelty and diversification: the WGD Radiation Lag-Time Model. Curr. Opin. Plant Biol. 15, 147153 (2012).

PubMed Google Scholar

Vanneste, K., Maere, S. & Peer, deY. V. Tangled up in two: a burst of genome duplications at the end of the Cretaceous and the consequences for plant evolution. Philos. Trans. R. Soc. B 369, 20130353 (2014).

Google Scholar

Tank, D. C. et al. Nested radiations and the pulse of angiosperm diversification: increased diversification rates often follow whole genome duplications. N. Phytologist 207, 454467 (2015).

Google Scholar

Soltis, P. S. & Soltis, D. E. Ancient WGD events as drivers of key innovations in angiosperms. Curr. Opin. Plant Biol. 30, 159165 (2016).

PubMed Google Scholar

Landis, J. B. et al. Impact of whole-genome duplication events on diversification rates in angiosperms. Am. J. Bot. 105, 348363 (2018).

PubMed Google Scholar

Cantino, P. D. et al. Towards a phylogenetic nomenclature of Tracheophyta. Taxon 56, 1E44E (2007).

Google Scholar

Jaillon, O. et al. The grapevine genome sequence suggests ancestral hexaploidization in major angiosperm phyla. Nature 449, 463467 (2007).

ADS CAS PubMed Google Scholar

Jiao, Y. et al. A genome triplication associated with early diversification of the core eudicots. Genome Biol. 13, R3 (2012).

PubMed PubMed Central Google Scholar

Vekemans, D. et al. Gamma paleohexaploidy in the stem-lineage of core eudicots: significance for MADS-box gene and species diversification. Mol. Biol. Evol. https://doi.org/10.1093/molbev/mss183 (2012).

Chanderbali, A. S., Berger, B. A., Howarth, D. G., Soltis, D. E. & Soltis, P. S. Evolution of floral diversity: genomics, genes and gamma. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 372, 20150509 (2017).

Soltis, D. E. et al. Gunnerales are sister to other core eudicots: implications for the evolution of pentamery. Am. J. Bot. 90, 461470 (2003).

PubMed Google Scholar

Endress, P. K. In Advances in Botanical Research 44: Developmental Genetics of the Flower (eds. Soltis, D. E., Leebens-Mack, J. H. & Soltis, P. S.) 161 (Elsevier, 2006).

Endress, P. K. Flower structure and trends of evolution in eudicots and their major subclades. Ann. Mo. Botanical Gard. 97, 541583 (2010).

Google Scholar

Soltis, D. E. et al. Angiosperm phylogeny: 17 genes, 640 taxa. Am. J. Bot. 98, 704730 (2011).

PubMed Google Scholar

Ohno, S. Evolution by Gene Duplication (Springer-Verlag, 1970).

Lyons, E., Pedersen, B., Kane, J. & Freeling, M. The value of nonmodel genomes and an example using SynMap within CoGe to dissect the hexaploidy that predates the rosids. Tropical Plant Biol. 1, 181190 (2008).

CAS Google Scholar

Ming, R. et al. Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.). Genome Biol. 14, R41 (2013).

PubMed PubMed Central Google Scholar

Tang, H. et al. Unraveling ancient hexaploidy through multiply-aligned angiosperm gene maps. Genome Res. 18, 19441954 (2008).

CAS PubMed PubMed Central Google Scholar

Akz, G. & Nordborg, M. The Aquilegia genome reveals a hybrid origin of core eudicots. Genome Biol. 20, 256 (2019).

PubMed PubMed Central Google Scholar

Velasco, R. et al. A high quality draft consensus sequence of the genome of a heterozygous grapevine variety. PLoS ONE 2, e1326 (2007).

ADS PubMed PubMed Central Google Scholar

Worberg, A. et al. Phylogeny of basal eudicots: insights from non-coding and rapidly evolving DNA. Org. Diversity Evolution 7, 5577 (2007).

Google Scholar

Ruhfel, B. R., Gitzendanner, M. A., Soltis, P. S., Soltis, D. E. & Burleigh, J. G. From algae to angiospermsinferring the phylogeny of green plants (Viridiplantae) from 360 plastid genomes. BMC Evolut. Biol. 14, 23 (2014).

Google Scholar

Moore, M. J., Soltis, P. S., Bell, C. D., Burleigh, J. G. & Soltis, D. E. Phylogenetic analysis of 83 plastid genes further resolves the early diversification of eudicots. Proc. Natl Acad. Sci. USA 107, 46234628 (2010).

ADS CAS PubMed PubMed Central Google Scholar

Sun, Y. et al. Phylogenomic and structural analyses of 18 complete plastomes across nearly all families of early-diverging eudicots, including an angiosperm-wide analysis of IR gene content evolution. Mol. Phylogenet. Evol. 96, 93101 (2016).

PubMed Google Scholar

Leebens-Mack, J. H. et al. One thousand plant transcriptomes and the phylogenomics of green plants. Nature 574, 679685 (2019).

Google Scholar

Filiault, D. L. et al. The Aquilegia genome provides insight into adaptive radiation and reveals an extraordinarily polymorphic chromosome with a unique history. Elife 7, e36426 (2018).

Strijk, J. S., Hinsinger, D. D., Zhang, F. & Cao, K. Trochodendron aralioides, the first chromosome-level draft genome in Trochodendrales and a valuable resource for basal eudicot research. Gigascience 8, giz136 (2019).

Liu, P.-L. et al. The Tetracentron genome provides insight into the early evolution of eudicots and the formation of vessel elements. Genome Biol. 21, 291 (2020).

CAS PubMed PubMed Central Google Scholar

Xu, Q., Jin, L., Zheng, C., Leebens-Mack, J. & Sankoff, D. in Lecture Notes in Bioinformatics Vol. 12686 (2021).

Chin, C.-S. et al. Phased diploid genome assembly with single-molecule real-time sequencing. Nat. Methods 13, 10501054 (2016).

CAS PubMed PubMed Central Google Scholar

Ghurye, J. et al. Integrating Hi-C links with assembly graphs for chromosome-scale assembly. PLoS Comput. Biol. 15, e1007273 (2019).

Yang, X., Lu, S. & Peng, H. Cytological studies on the eastern Asian family Trochodendraceae. Bot. J. Linn. Soc. 158, 332335 (2008).

Google Scholar

Van Laere, K., Hermans, D., Leus, L. & Van Huylenbroeck, J. Genetic relationships in European and Asiatic Buxus species based on AFLP markers, genome sizes and chromosome numbers. Plant Syst. Evolution 293, 111 (2011).

Google Scholar

Simo, F. A., Waterhouse, R. M., Ioannidis, P., Kriventseva, E. V. & Zdobnov, E. M. BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics 31, 32103212 (2015).

PubMed Google Scholar

Seppey, M., Manni, M. & Zdobnov, E. M. in Gene Prediction: Methods and Protocols (ed. Kollmar, M.) 227245 (Springer, 2019).

Ratter, J. A. & Milne, C. in Notes from the Royal Botanic Garden Edinburgh (UK) (1976).

Dodsworth, S., Chase, M. W. & Leitch, A. R. Is post-polyploidization diploidization the key to the evolutionary success of angiosperms?. Botanical J. Linn. Soc. 180, 15 (2016).

Google Scholar

Waterhouse, R. M. et al. BUSCO applications from quality assessments to gene prediction and phylogenomics. Mol. Biol. Evol. 35, 543548 (2018).

CAS PubMed Google Scholar

Johnson, M. G. et al. A universal probe set for targeted sequencing of 353 nuclear genes from any flowering plant designed using k-medoids clustering. Syst. Biol. 68, 594606 (2019).

CAS PubMed Google Scholar

Emms, D. M. & Kelly, S. OrthoFinder: phylogenetic orthology inference for comparative genomics. Genome Biol. 20, 238 (2019).

PubMed PubMed Central Google Scholar

Mirarab, S. & Warnow, T. ASTRAL-II: coalescent-based species tree estimation with many hundreds of taxa and thousands of genes. Bioinformatics 31, i44i52 (2015).

CAS PubMed PubMed Central Google Scholar

Sankoff, D., Zheng, C., Lyons, E. & Tang, H. in Algorithms for Computational Biology (eds. Botn-Fernndez, M., Martn-Vide, C., Santander-Jimnez, S. & Vega-Rodrguez, M. A.) 314 (Springer International Publishing, 2016).

Sankoff, D. & Zheng, C. in Comparative Genomics: Methods and Protocols (eds. Setubal, J. C., Stoye, J. & Stadler, P. F.) 291315 (Springer, 2018).

Murat, F., Armero, A., Pont, C., Klopp, C. & Salse, J. Reconstructing the genome of the most recent common ancestor of flowering plants. Nat. Genet 49, 490496 (2017).

CAS PubMed Google Scholar

Roach, M. J., Schmidt, S. A. & Borneman, A. R. Purge Haplotigs: allelic contig reassignment for third-gen diploid genome assemblies. BMC Bioinforma. 19, 460 (2018).

CAS Google Scholar

Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 21142120 (2014).

CAS PubMed PubMed Central Google Scholar

Grabherr, M. G. et al. Trinity: reconstructing a full-length transcriptome without a genome from RNA-Seq data. Nat. Biotechnol. 29, 644652 (2011).

CAS PubMed PubMed Central Google Scholar

Holt, C. & Yandell, M. MAKER2: an annotation pipeline and genome-database management tool for second-generation genome projects. BMC Bioinforma. 12, 491 (2011).

Google Scholar

Campbell, M. S. et al. MAKER-P: a tool kit for the rapid creation, management, and quality control of plant genome annotations. Plant Physiol. 164, 513524 (2014).

CAS PubMed Google Scholar

Ellinghaus, D., Kurtz, S. & Willhoeft, U. LTRharvest, an efficient and flexible software for de novo detection of LTR retrotransposons. BMC Bioinforma. 9, 18 (2008).

Google Scholar

Steinbiss, S., Willhoeft, U., Gremme, G. & Kurtz, S. Fine-grained annotation and classification of de novo predicted LTR retrotransposons. Nucleic Acids Res. 37, 70027013 (2009).

CAS PubMed PubMed Central Google Scholar

See original here:
Buxus and Tetracentron genomes help resolve eudicot genome history - Nature.com

Posted in Genome | Comments Off

Yale researcher receives award to investigate dark matter of the human genome – Yale Daily News

Posted: at 4:16 pm

Sarah Slavoffs work studying the dark matter of the human genome could lead to the development of more effective treatments for melanoma.

Elizabeth Watson 12:32 am, Feb 03, 2022

Staff Reporter

Courtesy of Elizabeth Watson

Sarah Slavoff, an associate professor of chemistry and of molecular biophysics and biochemistry, won the 2022 Emerging Leader Award from the Mark Foundation for Cancer Research for her work studying the dark matter of the human genome.

Slavoff, who was also recognized for the potential implications of her research in the fight against melanoma, will receive an annual grant of $250,000 for three years. The award will fund her project to investigate proteins that have not yet been identified and their links to melanoma, a type of severe skin cancer.

The work for the Mark Foundation is going to allow us to really deeply identify these genes that are associated with melanoma treatment resistance, or novel unannotated genes, to fully demonstrate their mechanisms of action so that we can understand what theyre doing and how thats affecting the tumor cells, Slavoff said.

Slavoff first became involved in this branch of research during her time as an NIH Ruth L. Kirschstein Postdoctoral Fellow at Harvard University. Although the Human Genome Project was officially completed in 2003, scientists suspected that there were parts of the genome that remained unknown. Alan Saghatelian, Slavoffs mentor at Harvard and the Dr. Frederik Paulsen Chair at the Salk Institute for Biological Studies, used mass spectrometry proteomics to study the proteins present in a given biological sample.

They discovered that, of the thousands of spectra that could be collected in a single experiment, there were some that could not be identified. While at Harvard, Slavoff played an important role in developing the first technologies to begin this identification process.

She [Slavoff] published several papers as a postdoc but the most notable was work describing the discovery of nearly 100 previously unknown microproteins, Saghatelian said. Her work showed a large class of unannotated microproteins that exist stably within cells, suggesting that microproteins should be able to function similarly to longer proteins and lay the foundation for functional studies to characterize these genes. Furthermore, the field has identified thousands of microproteins encoding genes in various genomes, and Dr. Slavoffs work was one of the critical findings that drove this field forward.

Slavoff continued researching this area in her own lab at the Yale Institute of Biomolecular Design and Discovery. Her work focuses on developing not only new methods to detect the unknown microproteins of the human genome, but also ways to understand its function.

The concept behind the term dark matter is that there are genes within the human genome, sometimes referred to as ghost proteins, that have always existed and been expressed but remained undetected because they were smaller than the cutoff size that is used to analyze the genome: 100 amino acid units.

Our hypothesis is that some of these novel genes in this dark matter of the proteome might be associated with the mechanisms by which melanoma escapes from current treatments, Slavoff said. If we can identify that, then we can learn something about those mechanisms, and even more importantly, hopefully an aspirational goal for the future is that they could inform new therapies.

A particular area of interest for Slavoff is the potential connection between dark matter and human diseases.

She has worked in conjunction with Ruth Halaban, a senior research scientist in dermatology at the Yale Cancer Center, to study its relationship in particular with metastatic melanoma.

Now were moving toward asking if this dark matter is linked to disease, and theres lots of preliminary evidence from other groups around the world that it is, Slavoff said. Were asking this specific question with the Mark Foundation about, really a pernicious problem, which are cancers that are drug-resistant or cant be treated.

There are two primary methods that are used to treat patients suffering from melanoma. Patients can either take drugs that can combat the driving enzymes within a tumor or undergo the process of immunotherapy to mobilize the immune system against the tumor. These methods, although capable of shrinking tumors, are not always effective. Roughly half of melanoma patients cannot be treated, according to Slavoff. By focusing upon this dark matter as opposed to the genes traditionally targeted by current treatments, Slavoff hopes to find a way to formulate more effective treatments for melanoma patients.

Jason Crawford, director of the Yale Institute for Biomolecular Design and Discovery, acknowledged the potential ramifications of the research being conducted by Slavoffs lab. He further noted the strong sense of teamwork that Slavoff fosters in her lab.

She is very caring for her students and is a strong mentor and tries to establish a sense of teamwork and team goals, Crawford said. Shes a leader in the area of microproteins, so she and her lab are really pushing the envelope in this new area, a largely understudied area.

Slavoff came to Yale in 2014.

Elizabeth Watson covers breakthrough research for SciTech and illustrates for various sections. She is a first year in Pauli Murray College and is planning to major in STEM and the humanities.

View original post here:
Yale researcher receives award to investigate dark matter of the human genome - Yale Daily News

Posted in Genome | Comments Off

Adaptation to genome decay in the structure of the smallest eukaryotic ribosome – Nature.com

Posted: at 4:16 pm

Isolation of E. cuniculi ribosomes

To improve our understanding of the evolution of proteins and nucleic acids in intracellular organisms, we set out to isolate E. cuniculi spores from infected mammalian cell cultures to purify their ribosomes and determine the structure of these ribosomes. Large quantities of microsporidian parasites are challenging to produce because microsporidians cannot be cultured in a growth medium. Instead, they grow and reproduce only inside their host cells. Therefore, to produce E. cuniculi biomass for the ribosome purification, we infected mammalian kidney cell line RK13 with E. cuniculi spores and cultivated these infected cells for several weeks to allow for E. cuniculi to grow and reproduce. Using approximately half a square meter of the infected cells monolayer, we could purify about 300mg of microsporidian spores and use them for ribosome isolation. We then broke the purified spores with glass beads and isolated crude ribosomes using a stepwise fractionation of lysates with polyethylene glycol. This allowed us to obtain approximately 300g of crude E. cuniculi ribosomes for structural analyses.

We then used the obtained ribosome sample to collect cryo-EM images and process these images with masks corresponding to the large ribosomal subunit, the head of the small subunit, and the body of the small subunit. In doing so, we collected snapshots of ~108,000 ribosomal particles and calculated cryo-EM maps at 2.7 resolution (Supplementary Figs.13). We then used the cryo-EM maps to build the model of rRNA, ribosomal proteins and the hibernation factor Mdf1 bound to E. cuniculi ribosomes (Fig.1a, b).

a The structure of E. cuniculi ribosomes in complex with the hibernation factor Mdf1 (pdb id 7QEP). b The map of the hibernation factor Mdf1 bound to E. cuniculi ribosomes. c Secondary structure diagrams compare rRNA reduction in microsporidian species with known ribosome structures. The panels indicate the location of rRNA expansion segments (ES) and ribosomal active centers, including the decoding site (DC), the sarcin-ricin loop (SRL), and the peptidyl-transferase center (PTC). d The electron density corresponding to the peptidyl-transferase center of E. cuniculi ribosomes shows that this catalytic site has the same structure in the parasite E. cuniculi and its hosts, including H. sapiens. e, f The electron density corresponding to the decoding center (e) and schematic structures of the decoding center (f) illustrate that E. cuniculi have U1491 residue instead of A1491 (E. coli numbering) in many other eukaryotes. This variation suggests that E. cuniculi may have sensitivity to the antibiotics targeting this active site.

Compared to the previously determined structures of V. necatrix and P. locustae ribosomes (both structures represent the same family of Nosematidae microsporidians and are very similar to each other)31,32, E. cuniculi ribosomes underwent further degeneration of numerous rRNA and proteins segments (Supplementary Figs.46). In rRNA, the most prominent changes include the complete loss of the 25S rRNA expansion segment ES12L and partial degeneration of helices h39, h41, and H18 (Fig.1c, Supplementary Fig.4). In ribosomal proteins, the most prominent changes include the complete loss of protein eS30 and truncations in proteins eL8, eL13, eL18, eL22, eL29, eL40, uS3, uS9, uS14, uS17, and eS7 (Supplementary Figs.4, 5).

Thus, the extreme genome reduction in Encephalotozoon/Ordospora species is reflected in the structure of their ribosomes: E. cuniculi ribosomes have experienced the most drastic loss of protein content among eukaryotic cytoplasmic ribosomes to be structurally characterized, and they are devoid of even those rRNA and protein segments that are widely conserved not only in eukaryotes but across the three domains of life. The structure of E. cuniculi ribosomes provided the first molecular model of these changes and revealed evolutionary events that were overlooked by both comparative genomics and structural studies of molecules from intracellular organisms (Supplementary Fig.7). Below, we describe each of these events, along with their possible evolutionary origin and their potential impact on ribosome function.

We next observed that, aside from large rRNA truncations, E. cuniculi ribosomes possess rRNA variations in one of their active sites. While the peptidyl-transferase center of E. cuniculi ribosomes has the same structure as in other eukaryotic ribosomes (Fig.1d), the decoding center differs due to the sequence variation in the nucleotide 1491 (E. coli numbering, Fig.1e, f). This observation is important because the decoding site of eukaryotic ribosomes typically contains residues G1408 and A1491, compared to bacteria-type residues A1408 and G1491. And this variation underlies different sensitivity of bacterial and eukaryotic ribosomes to the aminoglycoside family of ribosome-targeting antibiotics and other small molecules targeting the decoding site33,34,35. In the decoding site of E. cuniculi ribosomes, the A1491 residue is replaced with U1491, potentially creating a unique binding interface for small molecules targeting this active center. The same A14901 variation is present in other microsporidians, such as P. locustae and V. necatrix, suggesting its wide occurrence in microsporidian species (Fig.1f).

Because our samples of E. cuniculi ribosomes were isolated from metabolically inactive spores, we tested the cryo-EM maps of E. cuniculi for the presence of previously described hibernation factors that bind ribosomes under stress or starvation conditions31,32,36,37,38. We docked previously determined structures of hibernating ribosomes in the cryo-EM maps of E. cuniculi ribosomes. For this docking, we used Saccharomyces cerevisiae ribosomes in complex with the hibernation factor Stm138, P. locustae ribosomes in complex with the factor Lso232, and V. necatrix ribosomes in complex with factors Mdf1 and Mdf231. In so doing, we found the cryo-EM density corresponding to the hibernation factor Mdf1. Similar to Mdf1 binding to V. necatrix ribosomes, Mdf1 also binds E. cuniculi ribosomes, where it blocks the ribosomal E site, possibly helping inactivate ribosomes when parasites sporulate and become metabolically inactive (Fig.2).

Mdf1 blocks the ribosomal E site, which appears to help inactivate ribosomes when parasites sporulate and become metabolically inactive. In the structure of E. cuniculi ribosomes, we found that Mdf1 forms a previously unknown contact with the ribosomal L1-stalk (the part of the ribosome that helps release deacylated tRNAs from the ribosome during protein synthesis). These contacts suggest that Mdf1 dissociates from the ribosome using the same mechanism as deacetylated tRNAs, providing a possible explanation of how ribosomes can remove Mdf1 to reactivate protein synthesis.

Our structure, however, revealed a previously unknown contact between Mdf1 and the ribosomal L1-stalk (the part of the ribosome that helps release deacylated tRNAs from the ribosome during protein synthesis). Specifically, Mdf1 exploits the same contacts as the elbow-segment of deacylated tRNA molecules (Fig.2). This previously unknown molecular mimicry suggests that Mdf1 dissociates from the ribosome using the same mechanism as deacetylated tRNAs, explaining how ribosomes can remove this hibernation factor to reactivate protein synthesis.

While building the rRNA model, we found that E. cuniculi ribosomes possess anomalously folded rRNA segments, which we termed molten rRNA (Fig.3). In ribosomes across the three domains of life, rRNA folds into structures in which most rRNA bases are either base-paired and stacked with each other or interact with ribosomal proteins38,39,40. However, in E. cuniculi ribosomes, the rRNA appears to defy this folding principle by transforming some of their helices into unfolded rRNA stretches.

Structure of the helix H18 of the 25S rRNA in S. cerevisiae, V. necatrix, and E. cuniculi. Typically, in ribosomes across the three domains of life, this linker is folded into an RNA helix, which comprises between 24 and 34 residues. By contrast, in microsporidia this rRNA linker is being progressively reduced to two, single-stranded uridine-rich linkers that comprise just 12 residues. Most of these residues are exposed to the solvent. This figure illustrates that microsporidian parasites appear to defy a common principle of rRNA folding, in which rRNA bases are typically paired with other bases or involved in rRNAprotein interactions. In microsporidia, some rRNA segments adopt unfavorable folding, in which former rRNA helices are turned into single-stranded segments that are stretched out almost into a straight line. Having these unusual stretches allows microsporidian rRNA to connect distant segments of rRNA using the minimal number of RNA bases.

The most striking example of this evolutionary transformation can be observed in the helix H18 of the 25S rRNA (Fig.3). In species ranging from E. coli to humans, the base of this rRNA helix contains 24-32 nucleotides that form a slightly irregular helical structure. In the previously determined structures of ribosomes from V. necatrix and P. locustae31,32 the base of helix H18 is partially unwound yet the base-pairing of nucleotides is preserved. In E. cuniculi, however, this rRNA segment is turned into the minimal-length linkers 228UUUGU232 and 301UUUUUUU307. Unlike typical rRNA segments, these uridine-rich linkers are neither folded into a helix nor they are involved in extensive contacts with ribosomal proteins. Instead, they adopt a solvent-exposed and fully unfolded structure in which rRNA strands are stretched into an almost straight line. This stretched conformation explains how E. cuniculi can use just 12 RNA bases to fill the 33 -long gap between rRNA helices H16 and H18while other species require at least twice as many rRNA bases to fill this gap.

Thus, we could show that at the expense of energetically unfavorable folding, microsporidian parasites have invented a strategy to reduce even those rRNA segments that remain widely conserved across species from the three domains of life. Apparently, by accumulating mutations that transform rRNA helices into short poly-U linkers, E. cuniculi could evolve unusual rRNA segments that comprise the minimum possible number of nucleotides that is required to connect distant segments of rRNA. This helps explain how microsporidia have accomplished the phenomenal reduction of their essential molecular structure without losing its structural and functional integrity.

Another anomalous feature of E. cuniculi rRNA is the emerging of bulgeless rRNA (Fig.4). Bulges are non-base-paired nucleotides that flip out from RNA helices rather than being buried inside a helix41. Most rRNA bulges serve as a molecular glue by helping to bind adjacent ribosomal proteins or other rRNA segments. Some bulges serve as a hinge that allows rRNA helices to bend and adopt an optimal folding for productive protein synthesis41.

a rRNA bulges (S. cerevisiae numbering) that are missing in the structure of E. cuniculi ribosomes but present in most other eukaryotes b Comparison of the ribosome interior of E. coli, S. cerevisiae, H. sapiens and E. cuniculi illustrates that microsporidian parasites lack many ancient, highly conserved rRNA bulges. These bulges stabilize ribosome structure, therefore their absence in microsporidia suggests decreased stability of rRNA folding in microsporidian parasites. c Comparison with the P-stalk (L7/L12-stalk in bacteria) illustrates that the loss of rRNA bulges can occasionally co-occur with the emergence of new bulges in the vicinity of the lost ones. The helix H42 in 23S/28S rRNA possesses an ancient bulge (U1206 in S. cerevisiae), which is estimated to be at least 3.5 billion years old due to its conservation across the three domains of life. In microsporidia, this bulge has been eliminated; however, a new bulge (A1306 in E. cuniculi) has evolved in the vicinity of the lost one.

Strikingly, we observed that E. cuniculi ribosomes lack most of the rRNA bulges found in other species, including more than 30 bulges that are conserved in other eukaryotes (Fig.4a). This loss eliminates many contacts between ribosomal subunits and adjacent rRNA helices, occasionally creating large hollow voids within the ribosome interior, making E. cuniculi ribosomes more porous compared to the more conventional ribosomes (Fig.4b). Notably, we found that most of these bulges are also lost in the previously determined structures of V. necatrix and P. locustae ribosomes, which was overlooked by previous structural analyses31,32.

Occasionally, the loss of rRNA bulges is accompanied by the evolution of new bulges near the lost ones. For example, the ribosomal P-stalk contains a bulge U1208 (in S. cerevisiae) that is conserved from E. coli to humans and is therefore estimated to be 3.5 billion years old. During protein synthesis, this bulge helps the P-stalk to move between open and closed conformations so that the ribosome can recruit translation factors and deliver them to the active site42. In E. cuniculi ribosomes this bulge is missing; however, a new bulge (G883) is located just three base pairs away, possibly helping restore the optimal flexibility of the P-stalk (Fig.4c).

Our finding of bulgeless rRNA shows that rRNA minimization is not limited to the loss of rRNA elements on the surface of the ribosome but may affect the very core of the ribosome, creating a parasite-specific molecular defect that has not been observed in free-living species.

Having modelled canonical ribosomal proteins and rRNA, we found three segments of the cryo-EM map not accounted for by the conventional ribosome components. Two of these segments had a size of small molecules (Fig.5, Supplementary Fig.8). The first segment was sandwiched between ribosomal proteins uL15 and eL18 at a location normally occupied by the eL18 C-terminal truncated in E. cuniculi. Although we could not determine the identity of this molecule, the size and shape of this density island would be explained well by the presence of a spermidine molecule. Its binding to the ribosome is stabilized by microsporidia-specific mutations in protein uL15 (Asp51 and Arg56), which appear to increase the ribosome affinity to this small molecule as they allow uL15 to wrap around this small molecule in the ribosome structure (Supplementary Fig.8, Supplementary Data1, 2).

a The cryo-EM map indicates the presence of the extra-ribosomal nucleotide bound to the E. cuniculi ribosome. In the E. cuniculi ribosome this nucleotide occupies the same space as the 25S rRNA nucleotide A3186 (S. cerevisiae numbering) in most other eukaryotic ribosomes. b In the E. cuniculi ribosome structure, this nucleotide is being sandwiched between ribosomal proteins uL9 and eL20, stabilizing contacts between these two proteins. cd Analyses of eL20 sequence conservation in microsporidian species. A phylogenetic tree of microsporidian species (c) and a multiple sequence alignment of protein eL20 (d) illustrate that the nucleotide-binding residues F170 and K172 are conserved in most canonical microsporidia (aside from S. lophii), except for the early-branched microsporidia, in which the rRNA expansion ES39L is preserved. e The plot shows that the nucleotide-binding residues F170 and K172 are only found in eL20 from microsporidian parasites with highly reduced genomes and not in other eukaryotes. Overall, these data indicate that microsporidian ribosomes have evolved a nucleotide-binding site that appears to bind AMP molecules and use them to stabilize proteinprotein interactions in the ribosome structure. The high degree of conservation of this binding site among microsporidia and its absence in other eukaryotes indicates that this site may provide a selective advantage for microsporidia survival. Therefore, the nucleotide-binding pocket in microsporidian ribosomes appears not to be a vestigial feature or the ultimate form of rRNA degeneration, as previously suggested32, but a useful evolutionary innovation that allows microsporidian ribosomes to directly bind small molecules, utilizing them as molecular building blocks for ribosome assembly. This finding makes microsporidian ribosomes the only known ribosomes that use single nucleotides as a structural building block. f A hypothetic evolutionary path of the nucleotide-binding acquisition.

The second small molecule density was located at the interface of ribosomal proteins uL9 and eL30 (Fig.5a). This interface was previously described in the structure of S. cerevisiae ribosomes as a binding site of the 25S rRNA nucleotide A3186 (part of the rRNA expansion segment ES39L)38. In P. locustae ribosomes, where ES39L is degenerated, this interface was shown to bind an unidentified single nucleotide31, and it was hypothesized that this nucleotide represents the ultimate form of rRNA reduction in which the ~130-230 base-long rRNA expansion ES39L was reduced to a single nucleotide32,43. Our cryo-EM maps confirmed the idea that the density can be accounted for by a nucleotide. However, the higher resolution of our structure revealed that this nucleotide is an extra-ribosomal molecule, likely AMP (Fig.5a, b).

We next asked whether the nucleotide-binding site has been evolved or preexisted in E. cuniculi ribosomes. Because the nucleotide-binding is primarily mediated by residues Phe170 and Lys172 in the ribosomal protein eL30, we assessed the conservation of these residues in 4,396 representative eukaryotes. Similar to the aforementioned case of uL15, we found that Phe170 and Lys172 residues are highly conserved only in canonical microsporidia, but are absent in other eukaryotes, including non-canonical microsporidia Mitosporidium and Amphiamblys in which the rRNA ES39L segment is not reduced44,45,46 (Fig.5ce).

Collectively, these data supported the idea that E. cuniculi, and possibly other canonical microsporidians, have evolved the ability to effectively trap abundant small metabolites in their ribosome structures in order to compensate for the rRNA and protein reduction. In doing so, they have evolved the unique ability to bind extra-ribosomal nucleotides, illustrating a previously unknown and ingenious ability of parasitic molecular structures to compensate their degeneration by trapping small abundant metabolites and using them as structural mimics of degenerated RNA and protein segments.

The third unmodeled segment of the cryo-EM map we found within the large ribosomal subunit. The relatively high resolution of our maps (2.6) revealed that this density belongs to a protein with a unique combination of bulky side chains residues, which allowed us to identify this density as a previously unknown ribosomal protein, which we termed msL2 (microsporidia-specific protein L2) (Methods, Fig.6). Our homology search revealed that msL2 is conserved in the microsporidian branch of Encephalitozoon and Ordospora species but is absent in other species, including other microsporidians. In the ribosome structure, msL2 occupies a void formed by the loss of the rRNA expansion ES31L. In this void, msL2 helps stabilize rRNA folding and likely compensates for the ES31L loss (Fig.6).

a Electron density and model of the microsporidia-specific ribosomal protein msL2 found in E. cuniculi ribosomes. b Most eukaryotic ribosomes, including 80S ribosomes of S. cerevisiae, possess the rRNA expansion ES19L, which has been lost in most microsporidian species. The previously determined structure of microsporidian ribosomes from V. necatrix showed that the loss of ES19L in these parasites was compensated by the evolution of a new ribosomal protein, msL1. In this study, we discovered that E. cuniculi ribosomes also evolved an additional RNA-mimicking ribosomal protein as an apparent compensation for the loss of ES19L. However, msL2 (currently annotated as hypothetical protein ECU06_1135) and msL1 have different structure and evolutionary origin. c This finding of the birth of evolutionary unrelated ribosomal proteins msL1 and msL2 illustrates that ribosomes can achieve an unprecedented level of compositional diversity, even within a small group of closely related species, if they accumulate a deleterious mutation in their rRNA. This finding may help shed light on the origin and evolution of mitochondrial ribosomes, which are known for their severely reduced rRNA and exceptional variability of protein composition among species.

We next compared msL2 protein with the previously described protein msL1the only known microsporidia-specific ribosomal protein that was found in V. necatrix ribosomes31. We wanted to test whether msL1 and msL2 are evolutionary related to each other. Our analysis showed that msL1 and msL2 occupy the same cavity in the ribosome structure, but have distinct primary and tertiary structure, suggesting their independent evolutionary origin (Fig.6). Thus, our finding of msL2 provided evidence that close groups of eukaryotic species can independently evolve structurally distinct ribosomal proteins to compensate for the loss of rRNA segments. This finding is remarkable because most cytoplasmic eukaryotic ribosomes have invariant protein content, comprising the same set of 81 families of ribosomal proteins47. The birth of msL1 and msL2 in distinct microsporidian branches in response to the loss of the rRNA expansion segments suggests that degeneration of parasitic molecular structures forces parasites to seek compensatory mutations that may eventually lead to gain of compositional diversity of these structures in distinct groups of parasites.

Finally, when our model building was complete, we compared the composition of E. cuniculi ribosomes with the composition that was predicted based on genome sequence27. Previously, the E. cuniculi genome was predicted to lack several ribosomal proteins, including eL14, eL38, eL41, and eS30 due to the apparent absence of their homologs in the E. cuniculi genome27,48. The loss of multiple ribosomal proteins was also predicted in most other intracellular parasites and endosymbionts with highly reduced genomes49. For example, while most free-living bacteria contain the same set of 54 families of ribosomal proteins, only 11 of these protein families have detectable homologs in each of the analyzed genomes of host-restricted bacteria49. Supporting this idea, the loss of ribosomal proteins was observed experimentally in microsporidians V. necatrix and P. locustae, which both lack proteins eL38 and eL4131,32.

Our structure revealed, however, that only eL38, eL41, and eS30 are in fact lost in E. cuniculi ribosomes. The protein eL14 was retained, and our structure revealed why this protein could not be detected through homology search (Fig.7). In E. cuniculi ribosomes, most of the eL14-binding site is lost due to degeneration of the rRNA expansion ES39L. In the absence of ES39L, eL14 loses most of its secondary structure, and only 18% of the eL14 sequence is identical between E. cuniculi and S. cerevisiae. This poor sequence conservation is remarkable because even S. cerevisiae and H. sapiensorganisms that are separated by 1.5 billion years of evolutionpossess more than 51% identical residues in eL14. This extraordinary loss of conservation explains why E. cuniculi eL14 is currently annotated as hypothetical protein M970_061160 rather than ribosomal protein eL1427.

a Microsporidian ribosomes have lost the rRNA expansion ES39L, which partially eliminated the binding site for ribosomal protein eL14. In the absence of ES39L, microsporidian protein eL14 underwent a loss of secondary structure, in which former rRNA-binding -helices degenerated to minimal-length loops. b Multiple sequence alignment shows that protein eL14 is highly conserved among eukaryotic species (where it shares 57% sequence identity between yeast and human homologs), but poorly conserved and divergent among microsporidia (where no more than 24% of residues are identical to eL14 homologs from S. cerevisiae or H. sapiens). This poor sequence conservation, along with changes in the secondary structure, explains why homologs of eL14 have never been found in E. cuniculi and why this protein was thought to have been lost in E. cuniculi. Instead, E. cuniculi eL14 was previously annotated as the hypothetical protein M970_061160. This observation reveals that the diversity of microsporidian genomes is currently overestimated: some genes that are currently thought to have been lost in microsporidia are actually retained, although in a highly diverged form; conversely, some genes that are thought to encode microsporidia-specific proteins (e.g., hypothetical protein M970_061160) do in fact encode highly divergent proteins that can be found in other eukaryotes.

This finding illustrates that rRNA degeneration can lead to drastic loss of sequence conservation in adjacent ribosomal proteins, rendering these proteins undetectable for homology search. Hence, we may overestimate the actual extent of molecular degeneration in organisms with small genomes because some proteins that are viewed as lost are in fact preserved, though in a highly altered form.

More:
Adaptation to genome decay in the structure of the smallest eukaryotic ribosome - Nature.com

Posted in Genome | Comments Off

Record-breaking rapid DNA sequencing promises timely diagnosis for thousands of rare disease cases – Jacksonville Journal-Courier

Posted: at 4:16 pm

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

(THE CONVERSATION) For children suffering from rare diseases, it usually takes years to receive a diagnosis. This diagnostic odyssey is filled with multiple referrals and a barrage of tests, seeking to uncover the root cause behind mysterious and debilitating symptoms.

A new speed record in DNA sequencing may soon help families more quickly find answers to difficult and life-altering questions.

In just 7 hours, 18 minutes, a team of researchers at Stanford Medicine went from collecting a blood sample to offering a disease diagnosis. This unprecedented turnaround time is the result of ultra-rapid DNA sequencing technology paired with massive cloud storage and computing. This improved method of diagnosing diseases allows researchers to discover previously undocumented sources of genetic diseases, shining new light on the 6 billion letters in the human genome.

More than 7,000 rare diseases affect 300 million people worldwide, 50% of whom are children. Of these diseases, 80% have a genetic component. The onset of some rare genetic diseases can be swift and debilitating. Spotting symptoms and identifying the root cause is a race against the clock for many families.

Im a biotechnology and policy scholar who works on improving access to innovative health care technologies. Whether its simple and affordable tests or sophisticated and expensive gene therapies, medical breakthroughs need to reach populations around the world. I believe that ultra-rapid DNA sequencing is key to casting a wider net and providing a faster turnaround for diagnosing rare diseases.

A new Guinness World Record

The Human Genome Project, the first successful attempt to sequence a complete or whole human genome, took 13 years, from 1990 to 2003, and cost $2.7 billion. In 2014, the field of whole genome sequencing passed another major milestone by hitting the $1,000 price point. Every year, the cost of sequencing continues to fall, driven by engineering and computational innovation.

In their quest for a world record, Stanford researchers reached for a DNA sequencing platform from the company Oxford Nanopore Technologies, which developed a device that reads genomes by pulling large strands of DNA through pores comparable in size and composition to the openings in biological cell membranes. As a DNA strand passes through the pore, the device reads subtle electrical changes unique to each DNA letter, thus detecting the DNA sequence.

Thousands of these pores are distributed across a device called a flow cell. The researchers sequenced a single patients genome across 48 flow cells simultaneously, allowing them to read the entire genome in a record time of 5 hours, 2 minutes.

The ultra-rapid DNA sequencing generated terabytes of data, which was moved to a cloud-based storage system. In the cloud, algorithms scanned the genome, looking for tiny variations mutations within the DNA sequence that could help explain the origin of a genetic disease.

Rewriting the diagnostic odyssey

If a diseases origin is thought to reside in the genome, the standard medical way forward is to order a gene panel. This test sequences a list of predetermined genes for possible disease-causing mutations. Receiving test results usually takes two to three weeks but can take up to eight weeks, and can miss mutations in genes not on the list.

Shortening the sequencing and analysis process to seven hours and expanding the sequencing from a few genes to the entire genome could fundamentally alter the diagnostic odyssey. Ultra-rapid DNA sequencing has already made a difference in the lives of two children.

Matthew Junzman, a 13-year-old from Oregon, was rushed to Stanford Hospital and placed on life support. His heart was failing, and no one knew why. Doctors narrowed down the cause to two options: myocarditis, a reversible condition involving inflammation of the heart, or an untreatable genetic condition.

In the Stanford study, doctors performed an ultra-rapid DNA sequencing test, which quickly revealed that Matthew had a genetic condition. He was immediately placed on a transplant list and received a new heart three weeks later.

In the same study, a 3-month-old patient was admitted to the pediatric hospital suffering from seizures. Using the ultra-rapid DNA sequencing process, doctors quickly spotted a mutation in a gene that explained the seizures. Standard tests would have initially missed this diagnosis.

Disease diagnosis is a global problem

Advances in health care technology typically have a high price tag when they first become available. Corporate competition, cheaper materials and new generations of technology can help drive down costs. But infrastructure, political and regulatory hurdles all contribute to limiting global access.

While Oxford Nanopores technology is cheaper than several alternative sequencing devices, costs of equipment and materials are still prohibitively expensive for labs in many countries. Similarly, less than 20% of low- and middle-income countries have modern data infrastructure. This removes the possibility of cloud computing in many places.

Bringing ultra-rapid DNA sequencing to these countries will involve investing in regional efforts to support genomic research. For example, the Human Heredity & Health in Africa Initiative invests in scientific infrastructure and workforce development to study health and disease for African populations. Providing groups like these with the equipment and software needed for ultra-rapid DNA sequencing will ensure that rare diseases that are more common in African populations will not go unexplored.

There are no approved treatments for 95% of rare diseases. The limited number of individuals affected by a given rare disease makes it difficult to study symptoms and design clinical trials. Creating data-sharing systems and crafting regulations will be vital to allow people to safely share their personal information between countries. The European Joint Programme on Rare Diseases and the Global Alliance for Genomics & Health are making progress toward these goals, building bridges between rare disease communities around the world.

As ultra-rapid genome sequencing becomes a feature in hospitals across high-income countries, I believe its important to consider how the broader rare disease community will have access to these tools and benefit from the wave of new disease insight on the horizon.

[Understand new developments in science, health and technology, each week. Subscribe to The Conversations science newsletter.]

This article is republished from The Conversation under a Creative Commons license. Read the original article here: https://theconversation.com/record-breaking-rapid-dna-sequencing-promises-timely-diagnosis-for-thousands-of-rare-disease-cases-175480.

Follow this link:
Record-breaking rapid DNA sequencing promises timely diagnosis for thousands of rare disease cases - Jacksonville Journal-Courier

Posted in Genome | Comments Off

Science Talk – Sequencing, drugging and interpreting genomes: Where is genomics going next? – The Institute of Cancer Research, London – The Institute…

Posted: at 4:16 pm

The Festival of Genomics and Biodata the UK's largest genomics event, with more than 7,000 attendees is a great place for the global genomics community to meet.

Researchers from The Institute of Cancer Research, London, were present, including Professor Paul Workman, Professor Clare Turnbulland Dr Anguraj Sadanandam, who gave talks at the conference that ran from 25-28 January 2022.

Professor Dame Sue Hill, Chief Scientific Officer for NHS England, delivered the introductory keynote and explained how NHS England plans to keep up the momentum in genomics.

As she described, the UK holds a world-leading position in genomics, having been heavily involved in the Human Genome Project in the early 2000s and committed to sequencing 100,000 whole human genomes from patients with rare diseases and common cancers back in 2012.

Fast-forward to today and the NHS has launched the NHS Genomic Medicine Serviceand a world-first whole genome sequencing service, hoping to become the first national health care system to offer whole genome sequencing as part of routine care.

Next, the NHS and Genomics England will focus on the Cancer 2.0 initiative a proof of concept to explore the use of long-read sequencing (LRS) technology in cancer.

Our genome is too long to be sequenced in one go. Scientists often use short-read sequencing technology, where short fragments of DNA are sequenced separately and then pieced together. Long-read sequencing enables faster sequencing of longer fragments.

The hope is that the Cancer 2.0 project will introduce new technologies like this to support earlier, faster diagnosis cutting waiting times from weeks to days in some cases.

Another priority for Genomics England is diversity in genomic data. In the next few years, they hope to enrich their genomic datasets, sequencing cohorts of diverse backgrounds.

The ICRs Professor Paul Workman, Harrap Professor of Pharmacology and Therapeutics, delivered another of the opening keynote speeches, focusing on 'drugging' the cancer genome.

It has been 21 years since the human genome was first sequenced and released, and that has had an enormous impact of cancer drug discovery and development, he said.

New understanding of cancer genomes helps researchers identify new targets for drug development, and even repurpose drugs that already exist. So, putting it simply, using our knowledge of genomics increases the probability of drug development success.

This is hugely important, since the cost of drug discovery and development is prohibitive it costs around 2.6 billion dollars for a drug to come to the market and reach patients. This means that any help to pinpoint drug candidates as accurately as possible is desirable.

Despite all the investment in cancer research and discovering new cancer drugs, oncology has one of the lowest approval rates, at around 5 per cent and it takes an average of 10.5 years for a cancer drug to go from phase I trials to regulatory approval. There are many reasons for this delay from patent to patient highlighted in our Drug access report, which shows its particularly hard for innovative drugs to get rapid approval.

But using genetics across the drug development pipeline to validate targets and find biomarkers, for example is one of the first steps to help drug discovery efforts and re-purposing opportunities, ultimately benefiting patients.

Professor Workman also highlighted the important role of chemical probes in biomedical research and drug discovery. More publications come out when a chemical probe is identified, he said. Chemical probes are key to understanding a proteins role in biology and disease, which helps scientists in drug target validation and discovery.

There is a long way to go when it comes to drug development, and collaboration is key, explained Professor Workman:

Only around 9 per cent of patients actually have molecular targets that allow them to benefit from personalised medicine. For at least 90 per cent of patients, despite their genome sequence being available, there isnt currently a drug that works for them.

It takes a village. It takes basic research, universities, research institutes, pharma, biotech, regulators working together to do this better.

Professor Clare Turnbull spoke about genomics for early detection and prevention of cancer focusing on breast cancer as an example.

The field of genomics helps us understand and estimate peoples risk of developing cancer, which in turn helps us detect the disease as early as possible, or even prevent it. But cancer susceptibility genomics is complex, and researchers are still working out how to use their knowledge in the clinic.

There are specific inherited gene changes, also known as variants, which significantly increase cancer risk on their own such as variants of the BRCA1, BRCA2 or PALB2 genes. However, for most people, their genetic predisposition to cancer comes from the combined risk of many different variants. To understand this risk, scientists use so-called polygenic risk scores, which provide a snapshot of an individuals genetic risk.

So what can we do if we know certain people are at increased risk of certain cancers? Firstly, risk varies across tumour subtypes, and interventions vary in efficacy depending on the tumour subtype too. But by using their understanding of susceptibility genes and risk, clinicians can attempt to detect disease sooner thanks to screening programmes, or even prevent it using measures such as surgical prevention, chemoprevention or even behavioural changes.

One of Professor Turnbulls projects, BRCA-DIRECT, is exploring the usefulness of a digital platform to deliver genetic susceptibility testing, aiming to extend genetic testing to all women with breast cancer.

Aside from all the knowledge we can gain from genetic and genomic data, there are whole different sets of data and knowledge that can be used to power personalised medicine. Multi-omics also involves data ranging from proteomics, which focuses on proteins, to metabolomics, which involves the analysis of metabolism by-products.

Dr Anguraj Sadanandam talked about multi-omics data and how, with the help of AI and machine learning, we can make sense of the breadth of data available. By combining and integrating the data using these powerful technologies, we can understand whole systems we can obtain a much fuller picture of what goes wrong in cancer.

One of the machine learning tools that Dr Sadanandam uses in his lab is PhenMap, which helps to identify cancer subtypes and biomarkers by integrating different multi-omics data sets. He has been using PhenMap to reimagine clinical diagnoses of pancreatic neuroendocrine tumours helping define new subtypes of the disease and stratify for potential treatment opportunities.

We have come a long way since the inception of the Human Genome Project, launched more than two decades ago. From machine learning tools to drug development and susceptibility genes, there is no doubt that genomic research is delivering on promises we have been hearing about for a while but there is still a lot to accomplish.

As the curtain was drawn on the Festivals sixth year, George Freeman MP, Minister for Science, Research and Innovation, thanked all the attendees for a great week, assuring the audience that this is only the beginning: We are in the foothills of what, I think, is the most exciting revolution in healthcare.

View original post here:
Science Talk - Sequencing, drugging and interpreting genomes: Where is genomics going next? - The Institute of Cancer Research, London - The Institute...

Posted in Genome | Comments Off

Bionano Genomics Announces UK Footprint Expansion with Adoption of its Saphyr System for Optical Genome Mapping in Two Genetic Laboratory Hubs within…

Posted: at 4:16 pm

SAN DIEGO, Feb. 02, 2022 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (BNGO), pioneer of optical genome mapping (OGM) solutions on the Saphyr system and provider of NxClinical, the leading software solutions for visualization, interpretation and reporting of genomic data, today announced the adoption of its Saphyr system by two genetics laboratory hubs (GLH) within the United Kingdoms (UK) National Health Service (NHS). The Newcastle upon Tyne Hospitals NHS Foundation Trust and the Birmingham Womens and Children NHS Foundation Trust intends to utilize the system to evaluate OGM against traditional cytogenetic methods.

The UKs NHS is one of the worlds largest healthcare systems and is working to create a world class healthcare system using cutting edge genomic technologies. These adoptions significantly increase the footprint for OGM in the UK, complementing previous Saphyr placements in Belfast City Hospital in Belfast, Northern Ireland and Kings College Hospital in London, England.

The Newcastle upon Tyne Hospitals NHS Foundation Trust leads the North East and Yorkshire Genomic Laboratory Hub and is a partnership of hospitals and labs serving millions of people in these regions. The Birmingham Womens and Children NHS Foundation Trust leads the Central and South Genomic Laboratory Hub and is a consortium of labs serving 12 million residents in West Midlands, Oxford and Wessex. Both labs intend to evaluate the potential of OGM to detect chromosomal aberrations in hematologic malignancies, genetic conditions and specific solid tumors.

OGM has the potential to streamline a number of areas by replacing multiple analysis modalities with a single process, said Polly Talley, FRCPath, scientific lead for HaemOnc at the North East and Yorkshire Genomic Laboratory Hub. This could offer efficiency and speed to our genome analysis capabilities, and we are keen to see what this technology can provide to our HaemOnc service. Ms. Talleys colleague, Jennie Bell, Deputy Director/Consultant Clinical Scientist with the Central & South Genomic Laboratory Hub and Director, West Midlands Regional Genetics Laboratory, noted, We were encouraged by the positive experience reported by other laboratories using OGM technology, which included good detection resolution for genomic structural variations, a high level of automation and genome-wide analysis.

Story continues

With these two new Saphyr placements in the UKs NHS, we continue to broaden our footprint and provide scientists and clinical researchers with the ability to develop a comprehensive, reliable and cost-effective solution for detecting chromosomal abnormalities in hematologic malignancies, genetic conditions and cancer research applications, commented Erik Holmlin, PhD, President and Chief Executive Officer of Bionano. We welcome these genomic laboratory hubs to the OGM community and look forward to working with them as we strive to transform the way the world sees the genome.

About Bionano Genomics

Bionano Genomics is a provider of genome analysis solutions that can enable researchers and clinicians to reveal answers to challenging questions in biology and medicine. The Companys mission is to transform the way the world sees the genome through OGM solutions, diagnostic services, and software. The Company offers OGM solutions for applications across basic, translational and clinical research. Through its Lineagen business, the Company also provides diagnostic testing for patients with clinical presentations consistent with autism spectrum disorder and other neurodevelopmental disabilities. Through its BioDiscovery business, the Company also offers an industry-leading, platform-agnostic software solution, which integrates next-generation sequencing and microarray data designed to provide analysis, visualization, interpretation and reporting of copy number variants, single-nucleotide variants, and absence of heterozygosity across the genome in one consolidated view. For more information, visit bionanogenomics.com, lineagen.com or biodiscovery.com.

Forward-Looking Statements of Bionano Genomics

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the ability and utility of OGM and Saphyr to analyze genomes in a comprehensive, reliable and cost-effective way, the potential for OGM to become part of the standard of care and NHS continued use of the Saphyr system. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape, including the introduction of competitive technologies or improvements in existing technologies; failure of future results to support those found by NHS and referenced in this press release; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions, including NHS, to obtain funding to support adoption or continued use of our technologies; and the risks and uncertainties associated with our business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2020 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on managements assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations:Amy ConradJuniper Point+1 (858) 366-3243amy@juniper-point.com

Media Relations:Michael SullivanSeismic+1 (503) 799-7520michael@teamseismic.com

Read the original here:
Bionano Genomics Announces UK Footprint Expansion with Adoption of its Saphyr System for Optical Genome Mapping in Two Genetic Laboratory Hubs within...

Posted in Genome | Comments Off

PopHumanVar: Reconstructing the evolutionary past of the human species – EurekAlert

Posted: at 4:16 pm

image:PopHumanVar application view more

Credit: UAB

Throughout our evolutionary history, we have been subjected to persistent adaptive challenges: changes in environmental conditions as we left Africa and expanded to the rest of the planet; changes in diet as we replaced the hunting of wild animals and fruit picking with the domestication of animals and farming; and changes in encountering new pathogens when forming Neolithic settlements. Our adaptive responses to these selective pressures have left their signature in our genomes, something we can now identify and analyse in order to reconstruct our past.

In 2019, the research group Bioinformatics of Genomics Diversity from Universitat Autnoma de Barcelona (UAB) identified 2859 regions of the human genome that could be relevant to the understanding of human evolution, 873 of which had not been described before. The group, directed by Snia Casillas and Antonio Barbadilla, researchers at the Department of Genetics and Microbiology and at the Institute for Biotechnology and Biomedicine (IBB), thus provided a very valuable set of data to answer the question What makes us human?, and made it freely accessible through the PopHumanScan database.

The PopHumanScan catalogue was a first step in understanding which signatures had been left by selection on our genomes. Now, the research group has published the new interactive online resource PopHumanVar, which allows narrowing down these signatures, studying their origins and reconstructing the past of the human species. The new database makes it easier to explore and analyse the regions of the genome with evidence of having been the target of natural selection at a given point of our evolutionary history. This will help answering questions such as the functional causes of these mutations, when they occurred, and among which populations.

PopHumanVar collects, integrates and graphically represents functional and evolutionary genomic data from millions of genetic variants based on 2504 complete genomic sequences of 26 human populations from different parts of the world. Thanks to all the information collected, the database allows studying specific genomic regions with the aim of finding the mutations responsible for an adaptive event and discover when and where it first emerged. For example, PopHumanVar identifies the mutations responsible for well-known adaptive processes such as the EDAR gene in East Asian populations, involved in the development of hair follicles, teeth and sweat glands; the ACKR1 gene (DARC) in Africa, which plays a role in the inflammatory response and is associated with malaria resistance; and the one near the LCT gene in European populations, responsible for the digestion of lactose. Moreover, the application allows users to add and analyse their own data so that they can study adaptive processes in populations not included in the application.

The PopHumanVar application, which is the result of a study published by the researchers in the journal Nucleic Acid Research, represents a breakthrough in the study of human adaptation to different environments and big cultural changes during our expansion on Earth, and can be freely and easily accessed at: https://pophumanvar.uab.cat

The study that led to the creation of PopHumanVar is based on the international 1000 Genomes Project, the same one for which the UAB research group launched in 2018 PopHuman, the largest genome browser available on human genetic variation.

Nucleic Acids Research

Computational simulation/modeling

People

PopHumanVar: an interactive application for the functional characterization and prioritization of adaptive genomic variants in humans

19-Oct-2021

None declared

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

View post:
PopHumanVar: Reconstructing the evolutionary past of the human species - EurekAlert

Posted in Genome | Comments Off

Britain helping the Pasteur Institute of Montevideo with a Covid-19 genome-sequencing project – MercoPress

Posted: at 4:16 pm

Tuesday, February 1st 2022 - 09:55 UTC The data and analysis generated will provide public health staff a set of tools to assess the political answers to the pandemic

The British government and the Pasteur Institute of Montevideo, Uruguay, have announced they will be working jointly in an agreement that will help advance the genome-sequencing of Covid-19 project, through techniques under development in Uruguay, using British technology, and thus providing this capacity to several countries in the region.

The announcement was made during a meeting of James Dauris, Head of the Latin American Department, from the Foreign, Commonwealth and Development Office, currently visiting Uruguay, with the Director of the Pasteur Institute Montevideo, Carlos Batthyany, Uruguayan Health minister Daniel Salinas and Deputy minister Jose Luis Satdjian

Health minister Salinas said that through collaboration from both countries, the intention is for Uruguay to become a regional hub of scientific knowledge and added value. Many countries in Latin America and the Caribbean need a knowledge support plus labs, for the gnome-sequencing and the follow up of different plagues and viruses. We are betting on Uruguayan knowledge quality to provide them.

The data and analysis generated will provide public health staff a set of tools to assess the political answers to the pandemic, will supply an early alert system to face new variants, and guarantee the world scientific community will benefit through quality information, which for example, will help guarantee that vaccines continue to be the adequate for any new variants.

Dauris underlined that combating the pandemic has shown the importance of international collaboration. We are proud to work with the Pasteur Institute Montevideo to increase the capacity of making genome-sequencing in Uruguay, and thus support countries in the region in their fight against the pandemic

Pasteur Institute Montevideo chief Batthyany said that it was an honor for the Institute and we are very pleased to continue collaborating with the British Embassy, (as with other countries), with the purpose of improving the scientific networks in South America. We are analyzing the economic support offered by the British government to boost genome vigilance in real time in the region, measuring the capacity of the Institute to make such vigilance for Uruguay, besides other countries in the region

The project, involving some US$ 100,000 will be in charge of the Epidemiologic Vigilance Innovation Center, CIVE, to which the British government contributed funds for its foundation in 2020, together with the governments of France and the United States besides private organizations, corporations and citizens. The British Embassy and the Pasteur Institute Montevideo are drafting the agreement which they expect to have finalized and ready to sign very soon.

See original here:
Britain helping the Pasteur Institute of Montevideo with a Covid-19 genome-sequencing project - MercoPress

Posted in Genome | Comments Off

A role for ColV plasmids in the evolution of pathogenic Escherichia coli ST58 – Nature.com

Posted: at 4:16 pm

Foxman, B. The epidemiology of urinary tract infection. Nat. Rev. Urol. 7, 653660 (2010).

PubMed Google Scholar

Manges, A. R. et al. Global extraintestinal pathogenic Escherichia coli (ExPEC) lineages. Clin. Microbiol. Rev. 32, 125 (2019).

Google Scholar

Royer, G. et al. Phylogroup stability contrasts with high within sequence type complex dynamics of Escherichia coli bloodstream infection isolates over a 12-year period. Genome Med. 13, 77 (2021).

CAS PubMed PubMed Central Google Scholar

McKinnon, J., Roy Chowdhury, P. & Djordjevic, S. P. Genomic analysis of multidrug-resistant Escherichia coli ST58 causing urosepsis. Int. J. Antimicrob. Agents 52, 430435 (2018).

CAS PubMed Google Scholar

Roer, L. et al. WGS-based surveillance of third-generation cephalosporin-resistant Escherichia coli from bloodstream infections in Denmark. J. Antimicrob. Chemother. 72, 19221929 (2017).

CAS PubMed Google Scholar

Flament-Simon, S.-C. et al. High prevalence of ST131 subclades C2-H30Rx and C1-M27 among extended-spectrum -lactamase-producing Escherichia coli causing human extraintestinal infections in patients from two hospitals of Spain and France during 2015. Front. Cell Infect. Microbiol. 10, 125 (2020).

PubMed PubMed Central Google Scholar

Mamani, R. et al. Sequence types, clonotypes, serotypes, and virotypes of extended-spectrum -lactamase-producing Escherichia coli causing bacteraemia in a Spanish hospital over a 12-year period (2000 to 2011). Front. Microbiol. 10, 1530 (2019).

PubMed PubMed Central Google Scholar

Pietsch, M. et al. Whole genome analyses of CMY-2-producing Escherichia coli isolates from humans, animals and food in Germany. BMC Genomics 19, 601 (2018).

PubMed PubMed Central Google Scholar

Day, M. J. et al. Population structure of Escherichia coli causing bacteraemia in the UK and Ireland between 2001 and 2010. J. Antimicrob. Chemother. 71, 21392142 (2016).

CAS PubMed PubMed Central Google Scholar

Wang, S. et al. Antimicrobial resistance and molecular epidemiology of Escherichia coli causing bloodstream infections in three hospitals in Shanghai, China. PLoS ONE 11, e0147740 (2016).

PubMed PubMed Central Google Scholar

Irenge, L. M. et al. Whole-genome sequences of multidrug-resistant Escherichia coli in South-Kivu Province, Democratic Republic of Congo: characterization of phylogenomic changes, virulence and resistance genes. BMC Infect. Dis. 19, 137 (2019).

PubMed PubMed Central Google Scholar

Paramita, R. I. et al. Genome-based characterization of Escherichia coli causing bloodstream infection through next-generation sequencing. PLoS ONE 15, e0244358 (2020).

CAS PubMed PubMed Central Google Scholar

Dahmen, S., Mtayer, V., Gay, E., Madec, J.-Y. & Haenni, M. Characterization of extended-spectrum beta-lactamase (ESBL)-carrying plasmids and clones of Enterobacteriaceae causing cattle mastitis in France. Vet. Microbiol. 162, 793799 (2013).

CAS PubMed Google Scholar

Nesch-Inderbinen, M. et al. Molecular types, virulence profiles and antimicrobial resistance of Escherichia coli causing bovine mastitis. Vet. Rec. Open 6, e000369 (2019).

PubMed PubMed Central Google Scholar

Ali, A., Ali, Q., Ali, R. & Mohsin, M. Draft genome sequence of an extended-spectrum -lactamase-producing Escherichia coli ST58 isolate from cattle in Pakistan. J. Glob. Antimicrob. Resist. 21, 303305 (2020).

PubMed Google Scholar

Borges, C. A., Tarlton, N. J. & Riley, L. W. Escherichia coli from commercial broiler and backyard chickens share sequence types, antimicrobial resistance profiles, and resistance genes with human extraintestinal pathogenic Escherichia coli. Foodborne Pathog. Dis. 16, 813822 (2019).

CAS PubMed Google Scholar

Maamar, E. et al. High prevalence of extended-spectrum and plasmidic AmpC beta-lactamase-producing Escherichia coli from poultry in Tunisia. Int. J. Food Microbiol. 231, 6975 (2016).

CAS PubMed Google Scholar

Chah, K. F. et al. Detection and molecular characterisation of extended-spectrum -lactamase-producing enteric bacteria from pigs and chickens in Nsukka, Nigeria. J. Glob. Antimicrob. Resist. 15, 3640 (2018).

PubMed Google Scholar

Song, J., Oh, S.-S., Kim, J., Park, S. & Shin, J. Clinically relevant extended-spectrum -lactamase-producing Escherichia coli isolates from food animals in South Korea. Front. Microbiol. 11, 604 (2020).

PubMed PubMed Central Google Scholar

Ahmed, S., Olsen, J. E. & Herrero-Fresno, A. The genetic diversity of commensal Escherichia coli strains isolated from non-antimicrobial treated pigs varies according to age group. PLoS ONE 12, e0178623 (2017).

PubMed PubMed Central Google Scholar

Blaak, H. et al. Detection of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli on flies at poultry farms. Appl. Environ. Microbiol. 80, 239246 (2014).

ADS CAS PubMed PubMed Central Google Scholar

Vignaroli, C. et al. Multidrug-resistant and epidemic clones of Escherichia coli from natural beds of Venus clam. Food Microbiol. 59, 16 (2016).

CAS PubMed Google Scholar

Corts-Corts, G. et al. Detection and molecular characterization of Escherichia coli strains producers of extended-spectrum and CMY-2 type beta-lactamases, isolated from Turtles in Mexico. Vector Borne Zoonotic Dis. 16, 595603 (2016).

PubMed Google Scholar

Furlan, J. P. R., Lopes, R., Gonzalez, I. H. L., Ramos, P. L. & Stehling, E. G. Comparative analysis of multidrug resistance plasmids and genetic background of CTX-M-producing Escherichia coli recovered from captive wild animals. Appl. Microbiol. Biotechnol. https://doi.org/10.1007/s00253-020-10670-4 (2020).

Fuentes-Castillo, D. et al. Genomic characterization of multidrug-resistant ESBL-producing Escherichia coli ST58 causing fatal colibacillosis in critically endangered Brazilian merganser (Mergus octosetaceus). Transbound. Emerg. Dis. 68, 258266 (2021).

CAS PubMed Google Scholar

Mattioni Marchetti, V. et al. Deadly puppy infection caused by an MDR Escherichia coli O39 blaCTX-M-15, blaCMY-2, blaDHA-1, and aac(6)-Ib-cr - positive in a breeding Kennel in Central Italy. Front. Microbiol. 11, 584 (2020).

PubMed PubMed Central Google Scholar

de Carvalho, M. P. N. et al. International clones of extended-spectrum -lactamase (CTX-M)-producing Escherichia coli in peri-urban wild animals, Brazil. Transbound Emerg. Dis. https://doi.org/10.1111/tbed.13558 (2020).

Batalha de Jesus, A. A. et al. High-level multidrug-resistant Escherichia coli isolates from wild birds in a large urban environment. Microb. Drug Resist. 25, 167172 (2019).

CAS PubMed Google Scholar

Wyrsch, E. R. et al. Whole-genome sequence analysis of environmental Escherichia coli from the faeces of straw-necked ibis (Threskiornis spinicollis) nesting on inland wetlands. Microb. Genom. 6, 116 (2020).

Google Scholar

Wyrsch, E. R., Chowdhury, P. R., Jarocki, V. M., Brandis, K. J. & Djordjevic, S. P. Duplication and diversification of a unique chromosomal virulence island hosting the subtilase cytotoxin in Escherichia coli ST58. Microb. Genom. 6, (2020).

Zurfluh, K. et al. Antimicrobial resistant and extended-spectrum -lactamase producing Escherichia coli in common wild bird species in Switzerland. Microbiologyopen 8, e845 (2019).

CAS PubMed PubMed Central Google Scholar

Jamborova, I. et al. Plasmid-mediated resistance to cephalosporins and fluoroquinolones in various Escherichia coli sequence types isolated from rooks wintering in Europe. Appl. Environ. Microbiol. 81, 648657 (2015).

ADS PubMed PubMed Central Google Scholar

Skurnik, D. et al. Emergence of antimicrobial-resistant Escherichia coli of animal origin spreading in humans. Mol. Biol. Evol. 33, 898914 (2016).

CAS PubMed Google Scholar

Zurfluh, K. et al. Key features of mcr-1-bearing plasmids from Escherichia coli isolated from humans and food. Antimicrob. Resist. Infect. Control 6, 91 (2017).

PubMed PubMed Central Google Scholar

Ben Said, L. et al. Detection of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in vegetables, soil and water of the farm environment in Tunisia. Int. J. Food Microbiol. 203, 8692 (2015).

PubMed Google Scholar

Nesch-Inderbinen, M., Treier, A., Zurfluh, K. & Stephan, R. Raw meat-based diets for companion animals: a potential source of transmission of pathogenic and antimicrobial-resistant Enterobacteriaceae. R. Soc. Open Sci. 6, 191170 (2019).

ADS PubMed PubMed Central Google Scholar

Reid, C. J., Blau, K., Jechalke, S., Smalla, K. & Djordjevic, S. P. Whole genome sequencing of Escherichia coli from store-bought produce. Front. Microbiol. 10, 3050 (2019).

PubMed Google Scholar

Ferjani, S. et al. Community fecal carriage of broad-spectrum cephalosporin-resistant Escherichia coli in Tunisian children. Diagn. Microbiol. Infect. Dis. 87, 188192 (2017).

PubMed Google Scholar

Ben Sallem, R. et al. IncI1 plasmids carrying bla(CTX-M-1) or bla(CMY-2) genes in Escherichia coli from healthy humans and animals in Tunisia. Microb. Drug Resist. 20, 495500 (2014).

PubMed Google Scholar

Stterlin, S. et al. Silver resistance genes are overrepresented among Escherichia coli isolates with CTX-M production. Appl. Environ. Microbiol. 80, 68636869 (2014).

ADS PubMed PubMed Central Google Scholar

Teunis, P. F. M. et al. Time to acquire and lose carriership of ESBL/pAmpC producing E. coli in humans in the Netherlands. PLoS ONE 13, e0193834 (2018).

PubMed PubMed Central Google Scholar

Chen, P.-A. et al. Characteristics of CTX-M extended-spectrum -lactamase-producing Escherichia coli strains isolated from multiple rivers in Southern Taiwan. Appl. Environ. Microbiol. 82, 18891897 (2016).

ADS CAS PubMed PubMed Central Google Scholar

Sacramento, A. G. et al. Genomic analysis of MCR-1 and CTX-M-8 co-producing Escherichia coli ST58 isolated from a polluted mangrove ecosystem in Brazil. J. Glob. Antimicrob. Resist. 15, 288289 (2018).

PubMed Google Scholar

Ben Said, L. et al. Characteristics of extended-spectrum -lactamase (ESBL)- and pAmpC beta-lactamase-producing Enterobacteriaceae of water samples in Tunisia. Sci. Total Environ. 550, 11031109 (2016).

ADS PubMed Google Scholar

Denamur, E., Clermont, O., Bonacorsi, S. & Gordon, D. The population genetics of pathogenic Escherichia coli. Nat. Rev. Microbiol. https://doi.org/10.1038/s41579-020-0416-x (2020).

Galardini, M. et al. Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study. PLoS Genet. 16, e1009065 (2020).

CAS PubMed PubMed Central Google Scholar

Manges, A. R. Escherichia coli causing bloodstream and other extraintestinal infections: tracking the next pandemic. Lancet Infect. Dis. 19, 12691270 (2019).

PubMed Google Scholar

Moran, R. A. & Hall, R. M. Evolution of regions containing antibiotic resistance genes in FII-2-FIB-1 ColV-Colla virulence plasmids. Microb. Drug Resist 24, 411421 (2018).

CAS PubMed Google Scholar

Johnson, T. J. Role of plasmids in the ecology and evolution of High-Risk extraintestinal pathogenic Escherichia coli clones. Ecosal Plus 9, 117 (2021).

Google Scholar

Johnson, T. J. et al. Horizontal gene transfer of a ColV plasmid has resulted in a dominant avian clonal type of Salmonella enterica serovar Kentucky. PLoS ONE 5, e15524 (2010).

ADS CAS PubMed PubMed Central Google Scholar

Skyberg, J. A. et al. Acquisition of avian pathogenic Escherichia coli plasmids by a commensal E. coli isolate enhances its abilities to kill chicken embryos, grow in human urine, and colonize the murine kidney. Infect. Immun. 74, 62876292 (2006).

CAS PubMed PubMed Central Google Scholar

Xu, W.-Y., Li, Y.-J. & Fan, C. Different loci and mRNA copy number of the increased serum survival gene of Escherichia coli. Can. J. Microbiol. 64, 147154 (2018).

CAS PubMed Google Scholar

Posted in Genome | Comments Off

Page 503«..10 20..502503504 505..510 520..»

Category Archives: Transhuman News

Do Animals Understand What It Means to Die? – VICE

Buxus and Tetracentron genomes help resolve eudicot genome history – Nature.com

Yale researcher receives award to investigate dark matter of the human genome – Yale Daily News

Adaptation to genome decay in the structure of the smallest eukaryotic ribosome – Nature.com

Record-breaking rapid DNA sequencing promises timely diagnosis for thousands of rare disease cases – Jacksonville Journal-Courier

Science Talk – Sequencing, drugging and interpreting genomes: Where is genomics going next? – The Institute of Cancer Research, London – The Institute…

Bionano Genomics Announces UK Footprint Expansion with Adoption of its Saphyr System for Optical Genome Mapping in Two Genetic Laboratory Hubs within…

PopHumanVar: Reconstructing the evolutionary past of the human species – EurekAlert

Britain helping the Pasteur Institute of Montevideo with a Covid-19 genome-sequencing project – MercoPress

A role for ColV plasmids in the evolution of pathogenic Escherichia coli ST58 – Nature.com

The Prometheus League

Breaking News and Updates

Prometheism

Forbidden Fruit

The Evolutionary Perspective

Transtopia Menu

Library Updates

Library Books

Future Euvolution

Lucid Dreams from Childhood

Genetic Revolution

Speciation + Self-Directed Evolution