Researchers are using genomes from 241 species to redefine the mammalian tree of life

The research, led by a team of scientists from the Texas A&M School of Veterinary Medicine and Biomedical Sciences, ends the heated scientific debate about the history of mammalian diversification in relation to the extinction of the non-avian dinosaurs. Their work provides a definitive answer to the evolutionary timeline of mammals over the past 100 million years.

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

Texas A&M University research – led by Dr. William J. Murphy, Professor at the Department of Veterinary Integrative Biosciences, and Dr. Nicole Foley, Associate Research Scientist in Murphy’s lab – is rooted in phylogeny, a branch of biology concerned with the evolutionary relationships and diversification of living and extinct organisms.

“The central argument revolves around whether placental mammals (mammals that develop in placentas) diverged before or after the Cretaceous-Paleogene (or K-Pg) extinction event that wiped out the non-avian dinosaurs,” shared Foley with. “By conducting new types of analyzes that are only possible because of the vast scale of zoonomia, we are answering the question of where and when mammals diversified and evolved in relation to the K-Pg mass extinction event.”

The research – conducted with collaborators at the University of California, Davis; University of California, Riverside; and the American Museum of Natural History — concludes that mammalian diversification began before the K-Pg extinction as a result of continental drift, which caused Earth’s landmasses to drift apart and come back together over millions of years. Another surge in diversification occurred immediately after the K-Pg dinosaur extinction, when mammals had more space, resources, and stability.

This accelerated diversification led to 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 part of the Zoonomia project led by Elinor Karlsson and Kerstin Lindblad-Toh of the Broad Institute, which is also comparing mammalian genomes to understand the basis of remarkable phenotypes – expression of certain genes like brown vs. blue eyes – and the origins of diseases.

Foley pointed out that diversity among placental mammals is evident both in their physical characteristics and in their extraordinary abilities.

“Mammals today represent tremendous evolutionary diversity—from the swishing flight of the tiny bumblebee bat to the lazy gliding of the giant blue whale as it swims through the Earth’s vast oceans. Several species have evolved to echolocate, some produce venom, while others have evolved cancer resistance and virus tolerance,” she said.

“Being able to look at common differences and similarities between mammalian species at the genetic level can help us pinpoint the parts of the genome that are critical in regulating gene expression,” she continued. “Tweaking this genomic machinery across species has resulted in the diversity of traits we see in mammals alive today.”

Murphy shared that Foley’s resolved 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 Zoonomia project is really powerful because it’s the first analysis to match 241 different mammalian genomes at once and use that information to better understand the human genome,” he explained. “The main drive for compiling this large dataset was to be able to compare all of these genomes to the human genome and then determine which parts of the human genome changed over the course of mammalian evolutionary history.”

It is important for human medicine to determine which parts of genes can be manipulated and which parts cannot be changed without affecting the function of the gene. A recent study in Science Translational Medicine Led by a colleague of Murphy and Foley, 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 triggered by maternal loss of function UBE3A gene in the brain.

Dindot’s team took 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 data set in history will help develop more cures and treatments for the diseases of other species that are rooted in genetics, including cats and dogs.

“For example, cats have physiological adaptations rooted in unique mutations that allow them to eat 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 arrangement is that we can pick any species (not just humans) as a reference and determine which parts of that species’ genome are free to change and which cannot tolerate changes. In the case of cats, for example, we may be able to help identify genetic adaptations in these species that could lead to therapeutic targets for cardiovascular disease in humans.”

Murphy and Foley’s phylogeny also played a crucial role in much of the subsequent work that is part of the project.

“It’s trickle-down genomics,” Foley explained. “One of the most satisfying things for me about working on the larger project has been seeing how many different research projects have been improved by incorporating our phylogeny into their analyses. This ranges from conservation genomics studies of endangered species to those looking at the evolution of various complex human traits.”

Foley said it is both meaningful and rewarding to definitively answer the hotly debated question of when mammals evolved and create an expanded phylogeny that lays the foundation for the next generations of researchers.

“In the future, this massive genome comparison and its historical record of the evolution of the mammalian genome will be the basis for everything that anyone will do when asking comparative questions in mammals,” she said. “That’s pretty cool.”