Texas A&M research redefines mammalian tree of life
The research uses the genomes of 241 species and can be used to support animal and human health outcomes.
Peer-Reviewed PublicationResearch led by a team of scientists from the Texas A&M School of Veterinary Medicine and Biomedical Sciences puts to bed the heated scientific debate regarding the history of mammal diversification as it relates to the extinction of the non-avian dinosaurs. Their work provides a definitive answer to the evolutionary timeline of mammals throughout the last 100 million years.
The study, published in Science, is part of a series of articles released by the Zoonomia Project, a consortium of scientists from around the globe that is using the largest mammalian genomic dataset in history to determine the evolutionary history of the human genome in the context of mammalian evolutionary history. Their ultimate goal is to better identify the genetic basis for traits and diseases in people and other species.
The Texas A&M University research — led by Dr. William J. Murphy, a professor in the Department of Veterinary Integrative Biosciences, and Dr. Nicole Foley, an associate research scientist in Murphy’s lab — is rooted in phylogeny, a branch of biology that deals with the evolutionary relationships and diversification of living and extinct organisms.
“The central argument is about whether placental mammals (mammals that develop within placentas) diverged before or after the Cretaceous-Paleogene (or K-Pg) extinction event that wiped out the non-avian dinosaurs,” Foley shared. “By performing new types of analyses only possible because of Zoonomia’s massive scope, we answer the question of where and when mammals diversified and evolved in relation to the K-Pg mass extinction.”
The research — which was conducted with collaborators at the University of California, Davis; University of California, Riverside; and the American Museum of Natural History — concludes that mammals began diversifying before the K-Pg extinction as the result of continental drifting, which caused the Earth's land masses to drift apart and come back together over millions of years. Another pulse of diversification occurred immediately following the K-Pg extinction of the dinosaurs, when mammals had more room, resources and stability.
This accelerated rate of diversification led to the rich diversity of mammal lineages — such as carnivores, primates and hoofed animals — that share the Earth today.
Murphy and Foley’s research was funded by the National Science Foundation and is one part of the Zoonomia Project led by Elinor Karlsson and Kerstin Lindblad-Toh, of the Broad Institute, which also compares mammal genomes to understand the basis of remarkable phenotypes — the expression of certain genes such as brown vs. blue eyes — and the origins of disease.
Foley pointed out that the diversity among placental mammals is exhibited both in their physical traits and in their extraordinary abilities.
“Mammals today represent enormous evolutionary diversity — from the whizzing flight of the tiny bumblebee bat to the languid glide of the enormous Blue Whale as it swims through Earth’s vast oceans. Multiple species have evolved to echolocate, some produce venom, while others have evolved cancer resistance and viral tolerance,” she said.
“Being able to look at shared differences and similarities across the mammalian species at a genetic level can help us figure out the parts of the genome that are critical to regulate the expression of genes,” she continued. “Tweaking this genomic machinery in different species has led to the diversity of traits that we see across today’s living mammals.”
Murphy shared that Foley’s resolved phylogeny of mammals is crucial to the goals of the Zoonomia Project, which aims to harness the power of comparative genomics as a tool for human medicine and biodiversity conservation.
“The Zoonomia Project is really impactful because it's the first analysis to align 241 diverse mammalian genomes at one time and use that information to better understand the human genome,” he explained. “The major impetus for putting together this big data set was to be able to compare all of these genomes to the human genome and then determine which parts of the human genome have changed over the course of mammalian evolutionary history.”
Determining which parts of genes can be manipulated and which parts cannot be changed without causing harm to the gene’s function is important for human medicine. A recent study in Science Translational Medicine led by one of Murphy and Foley’s colleagues, Texas A&M geneticist Dr. Scott Dindot, used the comparative genomics approach to develop a molecular therapy for Angelman syndrome, a devastating, rare neurogenetic disorder that is triggered by the loss of function of the maternal UBE3A gene in the brain.
Dindot’s team took advantage of the same measures of evolutionary constraint identified by the Zoonomia Project and applied them to identify a crucial but previously unknown genetic target that can be used to rescue the expression of UBE3A in human neurons.
Murphy said expanding the ability to compare mammalian genomes by using the largest dataset in history will help develop more cures and treatments for other species' ailments rooted in genetics, including cats and dogs.
“For example, cats have physiological adaptations rooted in unique mutations that allow them to consume an exclusively high-fat, high-protein diet that is extremely unhealthy for humans,” Murphy explained. “One of the beautiful aspects of Zoonomia’s 241-species alignment is that we can pick any species (not just human) as the reference and determine which parts of that species’ genome are free to change and which ones cannot tolerate change. In the case of cats, for example, we may be able to help identify genetic adaptations in those species that could lead to therapeutic targets for cardiovascular disease in people.”
Murphy and Foley’s phylogeny also played an instrumental role in many of the subsequent papers that are part of the project.
“It’s trickle-down genomics,” Foley explained. “One of the most gratifying things for me in working as part of the wider project was seeing how many different research projects were enhanced by including our phylogeny in their analyses. This includes studies on conservation genomics of endangered species to those that looked at the evolution of different complex human traits.”
Foley said it was both meaningful and rewarding to definitively answer the heavily debated question about the timing of mammal origins and to produce an expanded phylogeny that lays the foundation for the next several generations of researchers.
“Going forward, this massive genome alignment and its historical record of mammalian genome evolution will be the basis of everything that everyone's going to do when they're asking comparative questions in mammals,” she said. “That is pretty cool.”
By Rachel Knight, Texas A&M University School of Veterinary Medicine & Biomedical Sciences
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JOURNAL
Science
ARTICLE TITLE
A genomic timescale for placental mammal evolution
ARTICLE PUBLICATION DATE
28-Apr-2023
New study reveals DNA analysis can help predict which animals face highest risk of extinction
Genomes from 240 mammal species could change how conservation efforts are applied
Peer-Reviewed PublicationDOWNLOAD VIDEO & PHOTOS AT: [https://sandiegozoo.box.com/s/xt7ea9blsdq9k10u3tkiw2o1fo77n79e]
SAN DIEGO (April 28, 2023) – A team of scientists led by San Diego Zoo Wildlife Alliance and University of California, Santa Cruz has discovered that animals’ genomic information can help predict which mammal species are more likely to face extinction.
Species with smaller historical populations carry higher burdens of damaging mutations and have elevated extinction risk, they found, which suggests that long-term demographic statistics are relevant to today’s conservation status and resiliency.
The findings, which could change how conservation actions and resources are strategically applied to help save endangered wildlife, are part of a series of papers from the Zoonomia Consortium that will be published this spring in a special issue of the renowned journal Science.
The planet is experiencing a rapid biodiversity loss, with tens of thousands of species at risk of dying out, and identifying the ones in most urgent need is a long and costly process. But there’s little information known about thousands of species, which makes it difficult to allocate limited conservation resources to target those closest to the brink.
To help circumvent these limitations, the scientists examined 240 mammal species, from tiny tree shrews to towering giraffes, killer whales and even humans. They found that the DNA encoded within a single genome – reflecting the species’ history over millions of years – can provide a rapid, cost-effective conservation risk assessment, even when we know little about the animals’ physiological, behavioral and life history characteristics, or even how many individuals remain.
“These results show that genetic information, even if only from a single individual for a given species, offers immediate, actionable guidance for scientists designing conservation strategies as well as those with boots in the field,” said Aryn P. Wilder, Ph.D., a conservation scientist at San Diego Zoo Wildlife Alliance and one of the paper’s two lead authors.
“The limited resources available for the conservation of wildlife species requires triage,” said Megan Supple, a research scientist with the UCSC Paleogenomics Lab and co-lead of the project. “Our genomic assessment provides a relatively inexpensive method to rapidly identify species at risk of becoming endangered in the future, even when little else is known about that species. This genomic triage enables managers to target limited resources toward species most in need.”
The genomic research was used to train models that quickly distinguish between threatened and non-threatened species, based on demography, diversity, and mutations that impact fitness. This will help assess extinction risk and identify which of the thousands of threatened species stand to benefit the most from conservation support, especially as the number of sequenced genomes grows and the models continue to improve.
Three species – the Upper Galilee Mountains blind mole rat, lesser chevrotain and orca – are highlighted as just three examples of the thousands of species lacking information on whether they’re threatened. The scientists applied their models to these “data-deficient” species to demonstrate how a genomic risk assessment could work.
What makes the research groundbreaking is the overall number of species included in the study, which is the largest of its kind. By examining 240 species, scientists were able to estimate the genomic characteristics that best predict extinction risk and build genomic risk assessment models that can be used when other information is lacking.
That led the paper’s authors to call for genomic information to be included in conservation status assessments of species, to bridge the gap between geneticists and conservation managers and provide a framework for deploying money and resources to species at highest risk.
“Many potentially endangered species are classified as ‘data deficient,’ meaning that we simply have too little information to determine whether immediate conservation action is required,” said Beth Shapiro, Ph.D., Professor of Ecology and Evolutionary Biology at UC Santa Cruz and an HHMI Investigator. “Our results show that a genome from a single individual can be sufficient to identify the most threatened of these ‘data deficient’ species, enabling us to focus our limited resources where they can be most impactful.”
“Our rapidly changing world threatens animal and plant species worldwide – but the use of genomics in conservation is a massive, underappreciated opportunity to protect them,” said Oliver Ryder, Ph.D., the Kleberg Endowed Director of Conservation Genetics at San Diego Zoo Wildlife Alliance and co-senior author of the paper.
“We are in an unprecedented era of discovery – a whole new way of seeing the world. We’ve long thought this potential existed, but it’s profound to see it crystallize into a catalyst that will help conservationists make crucial decisions that may save the world as we know it.”
The genomics manuscript is part of the work of the Zoonomia Consortium, the largest comparative mammalian genomics resource in the world, involving more than 150 people worldwide. The Science series papers also demonstrate how comparative genomics can shed light on how certain species achieve extraordinary feats, and help scientists better understand the parts of our genome that are functional and how they might influence health and disease. They also identified part of the genetic basis for rare mammal traits, such as the ability to sniff faint scents from miles away.
The San Diego Zoo Wildlife Alliance’s “Frozen Zoo” provided many of the genetic samples, including those of threatened and endangered species, for the DNA analyses performed at more than 50 institutions worldwide as part of the Zoonomia Consortium. The Frozen Zoo, or Wildlife Biodiversity Bank, is the largest repository of genetic material of its kind, containing viable cell cultures and reproductive material from approximately 10,000 animals representing over 1,100 species and subspecies.
The Zoonomia effort is led by Elinor Karlsson, Ph.D., director of the vertebrate genomics group at the Broad Institute of MIT and Harvard and a professor of bioinformatics and integrative biology at the UMass Chan Medical School, and Kerstin Lindblad-Toh, Ph.D., scientific director of vertebrate genomics at the Broad and a professor of comparative genomics at Uppsala University in Sweden.
About San Diego Zoo Wildlife Alliance
San Diego Zoo Wildlife Alliance is a nonprofit international conservation leader, committed to inspiring a passion for nature and working toward a world where all life thrives. The Alliance empowers people from around the globe to support their mission to conserve wildlife through innovation and partnerships. San Diego Zoo Wildlife Alliance supports cutting-edge conservation and brings the stories of their work back to the San Diego Zoo and San Diego Zoo Safari Park—giving millions of guests, in person and virtually, the opportunity to experience conservation in action. The work of San Diego Zoo Wildlife Alliance extends from San Diego to eco-regional conservation “hubs” across the globe, where their expertise and assets—including the renowned Wildlife Biodiversity Bank—are able to effectively align with hundreds of regional partners to improve outcomes for wildlife in more coordinated efforts. By leveraging these skills in wildlife care and conservation science, and through collaboration with hundreds of partners, San Diego Zoo Wildlife Alliance has reintroduced more than 44 endangered species to native habitats. Each year, San Diego Zoo Wildlife Alliance’s work reaches over 1 billion people in 150 countries via news media, social media, their websites, educational resources and the San Diego Zoo Wildlife Explorers television programming, which is in children’s hospitals in 13 countries. Success is made possible by the support of members, donors and guests to the San Diego Zoo and San Diego Zoo Safari Park, who are Wildlife Allies committed to ensuring all life thrives.
About the UC Santa Cruz Genomics Institute
The UC Santa Cruz Genomics Institute is one of the premier public institutions for storing, cataloging, assembling, validating, and analyzing huge volumes of genomic data. Its mission is to use genomics to positively impact health, nature, and society. It creates advanced technologies and open-source genomics platforms to unravel evolutionary patterns, molecular processes, and the underpinnings of disease. Its platforms, technologies, and scientists unite global communities to create and deploy data-driven, life-saving treatments and innovative conservation efforts. The Genomics Institute is dedicated to openly and responsibly sharing what it learns and creates in order to contribute to creating a healthier world.
JOURNAL
Science
METHOD OF RESEARCH
Data/statistical analysis
SUBJECT OF RESEARCH
Animals
ARTICLE TITLE
The contribution of historical processes to contemporary extinction risk in placental mammals
ARTICLE PUBLICATION DATE
28-Apr-2023
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