Daily Archives: August 11, 2017

August 11, 2017 A new paper from Duke molecular genetics and microbiology shows how pathogenic Cryptococcus fungi evolved from having many sexes to just two through 50 million years of gene swapping. Credit: Kara Manke

Biologically speaking, nearly every species on Earth has two opposite sexes, male and female. But with some fungi and other microbes, sex can be a lot more complicated. Some members of Cryptococcus, a family of fungus linked to human disease, can have tens of thousands of different mating types.

In a study appearing early online Aug. 11 in PLOS Biology, Duke researchers have mapped the evolutionary turning point that transformed the pathogenic form of Cryptococcus from an organism of many sexes to one with only two. They found that during evolution, a reshuffling of DNA known as translocation brought together separate chunks of sex-determining genes onto a single chromosome, essentially mimicking the human X or Y chromosome.

Surprisingly, they've shown that these crucial translocations occurred at the centromeres, the twisty ties that hold together chromosomes at the center of an x-shaped pair. These regions of the chromosome are so dense that they were once thought to be removed from recombination.

"Recombination at the centromere doesn't have to happen frequently, it just has to happen often enough that it punctuates the evolution of the organism," said Joseph Heitman, MD, PhD, senior study author and professor and chair of molecular genetics and microbiology at Duke University School of Medicine. "With each translocation, the genome is altered again and again, until you have evolved an entirely new species."

Scientists have been studying the evolution of sex chromosomes for more than a century. In the 1960's, Japanese-American geneticist and evolutionary biologist Susumu Ohno proposed a theory in which the genes determining sex first arose at various spots scattered across the entire genome, but over time were "captured" on the sex chromosomes. In humans, those chromosomes go by the familiar X and Y; in birds, they are known as Z and W; in moss, they are called U and V.

Regardless of the name or species, Heitman contends that some universal principles could govern the evolution of all sex chromosomes. He and an international team of researchers focused on the last common ancestor of the human pathogen Cryptococcus neoformans and its nearest sibling species, a non-pathogen called Cryptococcus amylolentus.

In C. amylolentus, dozens of genes at two different locations on the chromosomes control what's called a tetrapolar, or four-part, mating system. At one location or locus known as P/R, genes encode pheromones and pheromone receptors that help the fungus recognize compatible mating types. At the other locus, called HD, genes govern the development of sexual structures and reproductive spores.

The researchers sequenced the entire genome of C. amylolentus, mapping the location of all the genes as well as the centromeres on each of the organism's 14 chromosomes.

They found that the genomes had undergone quite a bit of rearrangement since the two species shared a common ancestor, at least 50 million years ago. For example, chromosome 1 of C. neoformans contained pieces of four different chromosomes from C. amylolentus, providing evidence of multiple translocations, some within the centromere.

"That was very surprising. The dogma has been that recombination is repressed in centromeric regions," said Sheng Sun, PhD, lead study author and assistant research professor at Duke University School of Medicine.

In the 1980's, a seminal paper by Duke colleague Tom Petes demonstrated recombination could occur across the centromeres in Saccharomyces cerevisiae, but some attributed the finding to a quirk of the favored model organism with its tiny point centromeres. But since then, other studies have emerged suggesting that the phenomenon was wider spread.

In this study, the researchers showed that in Cryptococcus amylolentus, the ancestral state, the P/R locus resided on chromosome 10 and the HD locus on chromosome 11. But in Cryptococcus neoformans, the evolved state, those loci ended up in one place. According to their model, multiple translocations deposited the two sex determinants on the same chromosome, with a centromere in between. Subsequent rearrangements put P/R and HD next to each other. The result was an organism with a bipolar mating system, much like the male and female sexes that embody most species.

"In any kind of model like this, you are thinking about what could have been the organization in the last common ancestor, which is now extinct so you can't know definitively," said Heitman. "But in each of these lineages, there are multiple evolutionary events that have occurred, and you can use genomics to turn back the hands of time and deduce the trajectory."

Heitman says their study suggests that other researchers should actively look for translocations, both in the expected locations as well as within centromeres. These chromosomal rearrangements are a common cause of birth defects and cancer in humans.

He and his colleagues are currently investigating whether similar translocations occur in the evolution of sex chromosomes in other fungal families, such as Ustilago and Malassezia.

Explore further: Evolution of the Sexes: What a Fungus Can Tell Us

More information: "Fungal genome and mating system transitions facilitated by chromosomal translocations involving intercentromeric recombination," Sheng Sun, Vikas Yadav, R. Blake Billmyre, Christina A. Cuomo, Minou Nowrousian, Liuyang Wang, Jean-Luc Souciet, Teun Boekhout, Betina Porcel, Patrick Wincker, Joshua A. Granek, Kaustuv Sanyal and Joseph Heitman. PLOS Biology, Early online Aug. 11, 2017. DOI: 10.1371/journal.pbio.2002527

Journal reference: PLoS Biology

Provided by: Duke University

Fungi don't exactly come in boy and girl varieties, but they do have sex differences. In fact, a new finding from Duke University Medical Center shows that some of the earliest evolved forms of fungus contain clues to how ...

For more than a decade, a rare but potentially deadly fungus called Cryptococcus deuterogatti has taken up residence in the Pacific Northwest and Vancouver Island. Unlike its cousin Cryptococcus neoformans, which mostly infects ...

In butterflies, sex is determined by chromosome differences between males and females. But unlike in humans with the familiar X and Y, in butterflies, it is the females that determine the sex of offspring.

As cells divide, some of their DNA is rearranged, spurring the emergence of new traits that can dictate whether a species survives or flounders. But some stretches of DNA appear to be so crucial to the basic functioning of ...

Researchers from Trinity College Dublin have uncovered the evolutionary mechanisms that have caused increases or decreases in the numbers of chromosomes in a group of yeast species during the last 100-150 million years. The ...

(Phys.org) -- Fruit flies are commonly used in genetics research because their lifespan is short, they are easy to breed in the laboratory, and mutants are widely available. There are about 1,500 known species. Now a new ...

Biologically speaking, nearly every species on Earth has two opposite sexes, male and female. But with some fungi and other microbes, sex can be a lot more complicated. Some members of Cryptococcus, a family of fungus linked ...

(Phys.org)A team of researchers with the University of Pennsylvania has uncovered the means by which squid eyes are able to adjust to underwater light distortion. In their paper published in the journal Science, the group ...

Scientists at the Universities of Oslo and Liverpool have uncovered the secret behind a goldfish's remarkable ability to produce alcohol as a way of surviving harsh winters beneath frozen lakes.

The gene-editing technology called CRISPR has revolutionized the way that the function of genes is studied. So far, CRISPR has been widely used to precisely modify single-celled organisms and, more importantly, specific types ...

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the current issue of Science, Nikolaus Rajewsky and his team at the ...

In the cells of palm trees, humans, and some single-celled microorganisms, DNA gets bent the same way. Now, by studying the 3-D structure of proteins bound to DNA in microbes called Archaea, University of Colorado Boulder ...

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Scientists map sex chromosome evolution in pathogenic fungi - Phys.Org

RENO, Nev. (News 4 & Fox 11)

Drift Evolution is one of the newest events at Reno's annual Hot August Nights, but it's quickly becoming one of the most popular.

Custom vehicles take turns drifting around a track at the Reno Livestock Events Center.

The event started in 2016, but this year, organizers said they sold out of participation passes about a month and a half before Hot August Nights started. They said they had to turn some drivers away because they didn't have enough space.

The cars featured at Drift Evolution are much different than the typical classic vehicles most people picture when they think of Hot August Nights. Many of them were built in the '90's and have been customized specifically for drifting.

Tickets to get into the Livestock Events Center are $10. Pit passes are an additional $10-- those allow access to talk to the drivers, see the drift cars up close, and take a lap as a passenger on the track.

Drift Evolution is happening through Saturday, August 12 from 9:00 a.m. to 8:00 p.m. CLICK HERE to learn more.

Continue reading here:

Drift Evolution puts modern spin on Hot August Nights - KRNV My News 4

August 11, 2017

How do initially benign forms of cancer evolve to become aggressive? In a quest to answer this long-standing question, an EU project has studied the growth and clonal evolution of chronic lymphocytic leukaemia (CLL)a blood and bone marrow cancer that mostly starts asymptomatic but can become very aggressive over time.

Cancer evolution is a complex process. Whilst we know that tumour growth is enabled by a continuous process of clonal expansion, genetic diversification and clonal selection, there are still many open questions related to this process. Answering them could be the key to preventing tumour progression and relapses.

According to Dr Michaela Gruber, whose research was funded under the CLL_INCLONEL (Identification and functional dissection of key genetic events in early chronic lymphocytic leukaemia) project, CLL is a valuable model for studying this process due to its high prevalence, initially slow progression and easy access to samples.

Dr Gruber studied the clonal dynamics of a cohort of 21 CLL patients, who were recurrently sampled from diagnosis until the time of first treatment. Her objectives were to identify events leading to disease progression using next-generation sequencing of patient samples. She also developed in vitro models to assess the functional impact of these genetic events on B cell biology, studied their impact on CLL and gathered valuable information on the effects of drugs on potential CLL sub-populations.

Dr Gruber agreed to discuss the project's outcomes and how they could one day lead to individualised diagnostic and therapeutic management of CLL.

What kind of knowledge did you aim to gather from this project?

The key aim of this project was to gain a better understanding of the early dynamics of growth and clonal evolution, as cancer progresses from diagnosis to the need for treatment. CLL is a highly informative model system for studying such natural cancer growth patterns: It typically has a relatively indolent beginning, with potentially long timeframes (in the order of years) before treatment becomes necessary.

Why is it so important to better understand clonal evolution? How can it help prevent tumour progression and relapse?

Insights from recent cancer sequencing studies indicate that the occurrence and expansion of cancer-driving mutations follows a specific sequence. Certain mutations generally appear to occur early in the disease and could be cancer-initiating. Other mutations tend to occur late and appear to have variable impact on tumour expansion. Moreover, different cancer sub-types show different patterns of mutations.

Together, these findings indicate that it could be possible to anticipate the specific evolutionary potential (i.e. plasticity) of a patient's cancer, which actually fuels progression, treatment resistance and relapse. Based on such understanding, therapeutic strategies could be shaped directly against this plasticity of cancer. This would be a major milestone towards overcoming current obstacles to cancer cure.

What would you say were the most important findings from the project?

Our data show that key mutations driving the progression of CLL are established very early in the course of the disease, years before symptoms warrant treatment initiation. For the first time, we were also able to quantify the impact of individual sub-clonal driver mutations on in vivo tumour expansion.

Another important discovery is that of clearly distinguishable growth patterns among patients, both globally as well as on a sub-clonal level. Finally, our data indicate that different patients have different potentials for clonal evolution and growth, and that these patterns remain throughout the entire course of the disease up to the event of relapse.

Can you tell us more about the genome editing technologies you employed?

Suitable experimental models are much needed in order to test the functional impact of observations made in CLL sequencing studies. Thus, we employed novel genome editing strategies, initially using TALENs and then switching to the recently emerged and more easily programmable CRISPR/Cas9 technology. Thanks to the latter, we established an array of isogenic B cell lines, which are used to test the molecular impact of mutations on cellular biology andmost importanttreatment response.

What are your plans now that the project is completed?

We have initiated several follow-up projects in Vienna, which aim to integrate an understanding of epigenetic modifications and tumour microenvironments, as well as their role and dynamics in CLL evolution.

What do you hope will be the impact of the project on future diagnostics and treatments?

Our hope is to establish cancer evolution as a predictable process. With sufficient understanding of the forces that drive evolution and selective advantages of sub-clonal mutations, we hope to develop prognostic schemes that anticipate individuals' evolutionary trajectories.

Treatments based on these schemes would directly aim to target the cancer plasticity that underlies progression, treatment resistance or relapse. CLL provides us with a unique opportunity to better understand cancer evolution. The conceptual insights about cancer that can thus be gained from CLL would have a high potential for being translated across other haematologic and solid malignancies.

Explore further: Follicular lymphoma: A tale of two cancers

More information: Project page: cordis.europa.eu/project/rcn/186119

Follicular lymphoma (FL), the second most common form of non-Hodgkin lymphoma, is a largely incurable disease of B cells, yet in many cases, because of its indolent nature, survival can extend to well beyond 10 years following ...

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CLL evolution under the microscope - Medical Xpress