Daily Archives: October 2, 2022

Every modern mammal, from a platypus to a blue whale, is descended from a common ancestor that lived about 180 million years ago. We dont know a great deal about this animal, but the organization of its genome has now been computationally reconstructed by an international team of researchers. The work is published Sept. 30 in Proceedings of the National Academy of Sciences.

Our results have important implications for understanding the evolution of mammals and for conservation efforts, said Harris Lewin, distinguished professor of evolution and ecology at the University of California, Davis, and senior author on the paper.

The researchers drew on high-quality genome sequences from 32 living species representing 23 of the 26 known orders of mammals. They included humans and chimps, wombats and rabbits, manatees, domestic cattle, rhinos, bats and pangolins. The analysis also included the chicken and Chinese alligator genomes as comparison groups. Some of these genomes are being produced as part of the Earth BioGenome Project and other large-scale biodiversity genome sequencing efforts. Lewin chairs the Working Group for the Earth BioGenome Project.

The reconstruction shows that the mammal ancestor had 19 autosomal chromosomes, which control the inheritance of an organisms characteristics outside of those controlled by sex-linked chromosomes, (these are paired in most cells, making 38 in total) plus two sex chromosomes, said Joana Damas, first author on the study and a postdoctoral researcher at the UC Davis Genome Center. The team identified 1,215 blocks of genes that consistently occur on the same chromosome in the same order across all 32 genomes. These building blocks of all mammal genomes contain genes that are critical to developing a normal embryo, Damas said.

The researchers found nine whole chromosomes, or chromosome fragments in the mammal ancestor whose order of genes is the same in modern birds chromosomes.

This remarkable finding shows the evolutionary stability of the order and orientation of genes on chromosomes over an extended evolutionary timeframe of more than 320 million years, Lewin said.

In contrast, regions between these conserved blocks contained more repetitive sequences and were more prone to breakages, rearrangements and sequence duplications, which are major drivers of genome evolution.

Ancestral genome reconstructions are critical to interpreting where and why selective pressures vary across genomes. This study establishes a clear relationship between chromatin architecture, gene regulation and linkage conservation, said Professor William Murphy, Texas A&M University, who was not an author on the paper. This provides the foundation for assessing the role of natural selection in chromosome evolution across the mammalian tree of life.

The researchers were able to follow the ancestral chromosomes forward in time from the common ancestor. They found that the rate of chromosome rearrangement differed between mammal lineages. For example, in the ruminant lineage (leading to modern cattle, sheep and deer) there was an acceleration in rearrangement 66 million years ago, when an asteroid impact killed off the dinosaurs and led to the rise of mammals.

The results will help understanding the genetics behind adaptations that have allowed mammals to flourish on a changing planet over the last 180 million years, the authors said.

Additional co-authors on the paper are: Marco Corbo, UC Davis; Jaebum Kim, Konkuk University, Seoul; Jason Turner-Maier, Bruce Birren, Diane Genereux, Jeremy Johnson, Kerstin Lindblad-Toh and Elinor Karlsson, Broad Institute of MIT and HarvardUniversity; Marta Farr, University of Kent, U.K.; Denis Larkin, University of London, U.K.; Oliver Ryder, Marlys Houck, Shaune Hall, Lily Shiue, Stephen Thomas, Thomas Swale, Mark Daly and Cynthia Steiner, San Diego Zoo Wildlife Alliance; Jonas Korlach, Pacific Biosciences; Marcela Uliano-Silva, Wellcome Trust Sanger Institute, Cambridge, U.K.; Camila J. Mazzoni, Berlin Center for Genomics in Biodiversity Research; Martin T. Nweeia, Harvard University and the Smithsonian Institution; and Rebecca Johnson, Australian Museum and University of Sydney; and members of the Zoonomia Consortium. The work was partly supported by the U.S. Department of Agriculture.

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Revealing the Genome of the Common Ancestor of All Mammals - University of California, Davis

The study also identified a new prostate cancer taxonomy.

Two groundbreaking studies recentlypublished in the journalsNature and Genome Medicine found genetic signatures that explain ethnic disparities in the severity of prostate cancer, notably in Sub-Saharan Africa.

By genetically analyzing prostate cancer tumors from Australian, Brazilian, and South African donors, the team developed a new prostate cancer taxonomy (classification scheme) and cancer drivers that not only distinguish patients based on their genetic ancestry but also predict which cancers are likely to become life-threatening, a task that is currently difficult.

Our understanding of prostate cancer has been severely limited by a research focus on Western populations, said senior author Professor Vanessa Hayes, genomicist and Petre Chair of Prostate Cancer Research at the University of Sydneys Charles Perkins Centre and Faculty of Medicine and Health in Australia. Being of African descent, or from Africa, more than doubles a mans risk for lethal prostate cancer. While genomics holds a critical key to unraveling contributing genetic and non-genetic factors, data for Africa has till now, been lacking.

Professor Vanessa Hayes examining a blood sample from a prostate cancer patient that was used in the study. Credit: Stefanie Zingsheim, University of Sydney

Prostate cancer is the silent killer in our region, said University of Pretorias Professor Riana Bornman, an international expert in mens health and clinical lead for the Southern African Prostate Cancer Study in South Africa. We had to start with a grassroots approach, engaging communities with open discussion, establishing the infrastructure for African inclusion in the genomic revolution, while determining the true extent of prostate disease.

Over two million cancer-specific genomic variants were identified in 183 untreated prostate tumors from males residing throughout the three research zones using advanced whole genome sequencing (a method of mapping the full genetic code of cancer cells).

We found Africans to be impacted by a greater number and spectrum of acquired (including cancer driver) genetic alterations, with significant implications for ancestral consideration when managing and treating prostate cancer, said Professor Hayes.

Using cutting-edge computational data science which allowed for pattern recognition that included all types of cancer variants, we revealed a novel prostate cancer taxonomy which we then linked to different disease outcomes, said Dr. Weerachai Jaratlerdsiri, a computational biologist from the University of Sydney and first author on the Nature paper.

Combining our unique dataset with the largest public data source of European and Chinese cancer genomes allowed us to, for the first time, place the African prostate cancer genomic landscape into a global context.

As part of her Ph.D. at the University of Sydney, Dr. Tingting Gong, the first author of the Genome Medicine paper, painstakingly sifted through the genomic data for large changes in the structure of chromosomes (molecules that hold genetic information). These changes are often overlooked because of the complexity involved in computationally predicting their presence, but are an area of critical importance and contribution to prostate cancer.

We showed significant differences in the acquisition of complex genomic variation in African and European derived tumors, with consequences for disease progression and new opportunities for treatment, said Dr. Gong.

This cancer genome resource is possibly the first and largest to include African data, in the world.

Through African inclusion, we have made the first steps not only towards globalizing precision medicine but ultimately to reducing the impact of prostate cancer mortality across rural Africa, explains Professor Bornman.

A strength of this study was the ability to generate and process all data through a single technical and analytical pipeline, added Professor Hayes.

The research featured in the Nature and Genome Medicine paper is part of the legacy of the late Archbishop Emeritus Desmond Tutu. He was the first African to have his complete genome sequenced, data which would be an integral part of genetic sequencing and prostate cancer research in southern Africa.

The results of the sequencing were published in Nature in 2010.

Diagnosed at age 66 with advanced prostate cancer, to which he succumbed in late December 2021, the Archbishop was an advocate not only for prostate cancer research in southern Africa, but also the benefits that genomic medicine would offer all peoples, recollected Professor Hayes.

We hope this study is the first step to that realization.

References:

African-specific molecular taxonomy of prostate cancer by Weerachai Jaratlerdsiri, Jue Jiang, Tingting Gong, Sean M. Patrick, Cali Willet, Tracy Chew, Ruth J. Lyons, Anne-Maree Haynes, Gabriela Pasqualim, Melanie Louw, James G. Kench, Raymond Campbell, Lisa G. Horvath, Eva K. F. Chan, David C. Wedge, Rosemarie Sadsad, Ilma Simoni Brum, Shingai B. A. Mutambirwa, Phillip D. Stricker, M. S. Riana Bornman, and Vanessa M. Hayes, 31 August 2022, Nature.DOI: 10.1038/s41586-022-05154-6

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers by Tingting Gong, Weerachai Jaratlerdsiri, Jue Jiang, Cali Willet, Tracy Chew, Sean M. Patrick, Ruth J. Lyons, Anne-Maree Haynes, Gabriela Pasqualim, Ilma Simoni Brum, Phillip D. Stricker, Shingai B. A. Mutambirwa, Rosemarie Sadsad, Anthony T. Papenfuss, Riana M. S. Bornman, Eva K. F. Chan and Vanessa M. Hayes, 31 August 2022, Genome Medicine.DOI: 10.1186/s13073-022-01096-w

Professor Hayes acknowledges the foresight of The Petre Foundation and donor Daniel Petre who has supported her vision for inclusive genomic research for over eight years.

Excerpt from:
Ancestral Heritage and Cancer: New Connection Discovered - SciTechDaily

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Revealing the uncharacterised diversity of amphibian and reptile viruses | ISME Communications - Nature.com

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Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany

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Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

Masaru Koido,Mingyang Shi,Yunye He&Yoichiro Kamatani

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

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Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Turku, Finland

Felix C. Vaura&Teemu J. Niiranen

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Rajendra Institute of Medical Sciences, Ranchi, India

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Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada

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The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

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From their use in basic biology to the development and testing of novel therapeutics, model organisms have helped to solve key scientific questions in experiments that are either impractical or unethical to conduct in humans. Important examples include rats, mice, zebrafish and non-human primates, often chosen for their likeness to humans in terms of anatomy, physiology or immunological response.

However, not all results gathered using model organisms can be translated to humans an acknowledged limitation of their use. A new genetic study of corals of the genus Acropora has emphasized this point further still, uncovering an unexpected pathway for the biosynthesis of an essential amino acid.

Cysteine (Cys) is an amino acid found in high abundance across many biological processes, such as protein synthesis and metabolism. In animals, the synthesis of cysteine was thought to occur via one specific pathway, known as the transsulfuration pathway, which involves the enzyme cystathionine -synthase (CBS) encoded by the CBS gene.

Researchers at the King Abdullah University of Science and Technology (KAUST) were studying corals of the Acroporoa genus, with the aim of generating a high-quality genome of Acropora loripes, a valuable genomic resource for future research. We werent searching for possible cysteine biosynthesis inAcropora, says Dr. Octavio Salazar, a postdoc in The Coral Symbiomics lab at KAUST, and lead author of the study.

And yet thats exactly what the researchers found; a surprise, considering that previous work had suggested the CBS gene had been lost in these corals, meaning they must rely on symbiotic relationships with algae to receive cysteine.

Once the genome was complete, Salazar and colleagues searched for proof that the CBS gene was in fact absent. It was, but Salazar remained skeptical.

I started searching the genome for genes encoding for enzymes that looked similar to those in other known cysteine biosynthesis pathways, such as those found in fungi and bacteria, says Salazar. I was quite surprised to find two enzymes in the coral with similarities to a recently identified alternative cysteine biosynthesis pathway in fungi.

The research team used yeast mutants that are completely unable to synthesize cysteine, and inserted the genes found in Acropora. Interestingly, the mutant yeast began to produce cysteine, indicating that the enzymes encoded by the genes found in the coral could synthesize the amino acid in vivo.

When looking further afield in the genomic landscape, Salazar and colleagues found that the genes were also present in the genomes of all animal phyla, except for vertebrates, nematodes and arthropods. As these three groups are the source of the most common model organisms used in scientific research, the team advise caution when it comes to overlying on findings from animal models.

This study proves the value of keeping an open mind when it comes to studying living creatures, says principal investigator Professor Manuel Aranda from KAUST. Sometimes knowledge can put you in a box; if you analyze data using only what you think you know, you may well miss something. OurAcroporagenome will be hugely valuable for future studies and who knows, it could reveal other unexpected details along the way.

Reference: Salazar OR, N. Arun P, Cui G, et al. The coral Acropora loripes genome reveals an alternative pathway for cysteine biosynthesis in animals. Sci Adv. 2022 8(38):eabq0304. doi:10.1126/sciadv.abq0304.

This article is a rework of a press release issued by KAUST university. Material has been edited for length and content.

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Unexpected Production of Cysteine Amino Acid Found in Coral - Technology Networks

When the first humans moved out of Africa, they carried their gut microbes with them. Turns out, these microbes also evolved along with them.

The human gut microbiome is made up of hundreds to thousands of species of bacteria and archaea. Within a given species of microbe, different strains carry different genes that can affect your health and the diseases you're susceptible to.

There is pronounced variation in the microbial composition and diversity of the gut microbiome between people living in different countries around the world. Although researchers are starting to understand what factors affect microbiome composition, such as diet, there is still limited understanding on why different groups have different strains of the same species of microbes in their guts.

We are researchers who study microbial evolution and microbiomes. Our recently published study found that not only did microbes diversify with their early modern human hosts as they traveled across the globe, they followed human evolution by restricting themselves to life in the gut.

We hypothesized that as humans fanned out across the globe and diversified genetically, so did the microbial species in their guts. In other words, gut microbes and their human hosts "codiversified" and evolved together just as human beings diversified so that people in Asia look different from people in Europe, so too did their microbiomes.

To assess this, we needed to pair human genome and microbiome data from people around the world. However, data sets that provided both the microbiome data and genome information for individuals were limited when we started this study. Most publicly available data was from North America and Western Europe, and we needed data that was more representative of populations around the world.

So our research team used existing data from Cameroon, South Korea and the United Kingdom, and additionally recruited mothers and their young children in Gabon, Vietnam and Germany. We collected saliva samples from the adults to ascertain their genotype, or genetic characteristics, and fecal samples to sequence the genomes of their gut microbes.

For our analysis, we used data from 839 adults and 386 children. To assess the evolutionary histories of humans and gut microbes, we created phylogenetic trees for each person and as well as for 59 strains of the most commonly shared microbial species.

When we compared the human trees to the microbial trees, we discovered a gradient of how well they matched. Some bacterial trees didn't match the human trees at all, while some matched very well, indicating that these species codiversified with humans. Some microbial species, in fact, have been along for the evolutionary ride for over hundreds of thousands of years.

We also found that microbes that evolved in tandem with people have a unique set of genes and traits compared with microbes that had not codiversified with people. Microbes that partnered up with humans have smaller genomes and greater oxygen and temperature sensitivity, mostly unable to tolerate conditions below human body temperature.

In contrast, gut microbes with weaker ties to human evolution have traits and genes characteristic of free-living bacteria in the external environment. This finding suggests that codiversified microbes are very much dependent on the environmental conditions of the human body and must be transmitted quickly from one person to the next, either passed down generationally or between people living in the same communities.

Confirming this mode of transmission, we found that mothers and their children had the same strains of microbes in their guts. Microbes that were not codiversified, in contrast, were more likely to survive well outside of the body and may be transmitted more widely through water and soil.

Our discovery that gut microbes evolved right along with their human hosts offers another way to view the human gut microbiome. Gut microbes have passed between people over hundreds to thousands of generations, such that as humans changed, so did their gut microbes. As a result, some gut microbes behave as though they are part of the human genome: They are packages of genes that are passed between generations and shared by related individuals.

Personalized medicine and genetic testing are starting to make treatments more specific and effective for the individual. Knowing which microbes have had long-term partnerships with people may help researchers develop microbiome-based treatments specific to each population. Clinicians are already using locally sourced probiotics derived from the gut microbes of community members to treat malnutrition.

Our findings also help scientists better understand how microbes transition ecologically and evolutionarily from "free-living" in the environment to dependent on the conditions of the human gut. Codiversified microbes have traits and genes reminiscent of bacterial symbionts that live inside insect hosts. These shared features suggest that other animal hosts may also have gut microbes that codiversified with them over evolution.

Paying special attention to the microbes that share human evolutionary history can help improve understanding of the role they play in human well-being.

Taichi A. Suzuki, Postdoctoral Research Associate in Microbiome Science, Max Planck Institute for Biology and Ruth Ley, Director, Department of Microbiome Science, Max Planck Institute for Biology

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Like genes, your gut microbes pass from one generation to the next - Salon