Researchers use the genomes of 241 species to redefine the mammalian tree of life

The research, led by a team of scientists from Texas A&M’s School of Veterinary Medicine and Biomedical Sciences, refocuses a heated scientific debate about the history of mammalian diversification as it relates to the extinction of the non-avian dinosaurs. Their work provides a definitive answer to the timeline of mammalian evolution over the past 100 million years.

A study published Science, is part of a series of papers published by the Zoonomia Project, a consortium of scientists from around the world using the largest mammalian genome dataset in history to determine the evolutionary history of the human genome in the context of mammalian evolutionary history. Their main goal is to better identify the genetic basis of traits and diseases in humans and other species.

A Texas A&M University study led by Dr. William J. Murphy, Professor in the Department of Veterinary Integrative Biosciences and Dr. Nicole Foley, a research associate in the Murphy lab, has roots in phylogeny, the branch of biology that deals with the evolutionary relationships and diversification of living and extinct organisms.

“The main argument is whether placental mammals (mammals that develop in the placenta) diverged before or after the Cretaceous-Paleogene (or K-Pg) extinction event that wiped out the non-avian dinosaurs,” Foley shared. “Through a new type of analysis only possible because of the vast scope of Zoonomia, we are answering the question of where and when mammals diversified and evolved in relation to the K-Pg mass extinction.”

The study, conducted with collaborators at the University of California, Davis; University of California, Riverside; and the American Museum of Natural History—concludes that mammals began to diversify before the K-Pg extinction as a result of continental drift, which caused Earth’s land masses to drift and rejoin over millions of years. Another spurt of diversification occurred immediately after the K-Pg extinction of the dinosaurs, when mammals had more space, resources, and stability.

This accelerated rate of diversification resulted in the rich diversity of mammalian lineages such as carnivores, primates, and ungulates 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 mammalian genomes to understand the basis of remarkable phenotypes — certain genes such as brown or blue eyes, and the origin of diseases.

Foley pointed out that the diversity of placental mammals is reflected in both their physical characteristics and their unusual abilities.

“Mammals today represent an enormous evolutionary diversity, from the whistling flight of the tiny bumblebee bat to the feeble glide of the giant blue whale as it swims across Earth’s vast oceans. Several species have evolved to echo, some produce poisons, and others have developed cancer. resistance and tolerance to viruses, ” she said.

“Being able to look at shared differences and similarities between mammalian species at the genetic level can help us elucidate parts of the genome that are essential for regulating gene expression,” she continued. “The adaptation of this genomic machinery in different species has led to the diversity of traits we see in modern living mammals.”

Murphy shared that Foley’s resolution of the mammalian phylogeny is critical 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 Zonomy project is really impactful because it’s the first analysis to align 241 different mammalian genomes at once and use that information to better understand the human genome,” he explained. “The main impetus for compiling this large data set was to be able to compare all 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 and cannot be manipulated without harming gene function is important for human medicine. A recent study Science Translational Medicine one of Murphy and Foley’s colleagues, Texas A&M geneticist Dr. Scott Dindot, used a comparative genomics approach to develop a molecular therapy for Angelman syndrome, a devastating, rare neurogenetic disorder caused by loss of maternal function. UBE3A gene in the brain.

Dindot’s team took the same measures of evolutionary constraints identified by the Zoonomia project and used them to identify an essential but previously unknown genetic target that can be used to rescue UBE3A in human neurons.

Expanding the ability to compare mammalian genomes with the largest data set in history will help develop more drugs and treatments for diseases rooted in genetics in other species, including cats and dogs, Murphy said.

“For example, cats have physiological adaptations rooted in unique mutations that allow them to consume only a high-fat, high-protein diet that is extremely unhealthy for humans,” Murphy explained. “One of the beautiful things about aligning Zoonomia’s 241 species is that we can take any species (not just humans) as a reference and determine which parts of that species’ genome can and cannot tolerate change. For example, we can help identify genetic adaptations for them species that could lead to therapeutic targets for human cardiovascular disease.

Murphy and Foley’s phylogeny also played an important role in many of the subsequent papers that are part of the project.

“It’s leaky genomics,” Foley explained. “One of the most gratifying things for me about working on the larger project was seeing how many different research projects were enhanced by incorporating our phylogeny into their analyses. This includes studies on conservation genomics for endangered species and those that looked at the evolution of various complex human traits.”

Foley said it is both meaningful and rewarding to accurately answer the much-debated question of the origin of mammals and create an extended 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 underpin everything anyone does when they ask comparative questions about mammals,” she said. “That’s pretty cool.”