Texas A&M research changes 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 puts an end to the heated scientific debate about the history of mammalian diversification linked to the extinction of non-avian dinosaurs. Their work provides a definitive answer to the timeline of mammalian evolution throughout the last 100 million years.

Studies published in Science, is part of a series of articles released by the Zoonomia Project, a consortium of scientists from around the world that uses the largest mammal genome dataset in history to determine the evolutionary history of the human genome in the context of the evolutionary history of mammals. Their main 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. 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 — has its roots in phylogeny, the branch of biology that deals with the evolutionary and diversification relationships 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. “By performing a new type of analysis made possible only because of Zoonomia’s wide scope, we address questions about where and when mammals diversified and evolved in relation to the K-Pg mass extinction.”

Research — conducted with collaborators at the University of California, Davis; University of California, Riverside; and the American Museum of Natural History — concluded that mammals began to diversify before the K-Pg extinction as a result of continental drift, which caused Earth’s continents to separate and reunite over millions of years. Another pulse of diversification occurred in the immediate aftermath of the K-Pg dinosaur extinction, 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 extraordinary phenotypic basis — the expression of certain genes such as brown eyes vs. blue — and the origin of disease.

Foley showed that the diversity among placental mammals is demonstrated both in their physical properties and in their extraordinary abilities.

“Today’s mammals represent enormous evolutionary diversity — from the whizzing flight of tiny bee-bats to the languid gliding of enormous Blue Whales as they swim through Earth’s vast oceans. Some species have evolved to echolocate, some produce toxins, while others have developed cancer resistance and virus tolerance,” he said.

“Being able to see the shared differences and similarities across mammalian species at the genetic level can help us figure out which parts of the genome are critical for regulating gene expression,” he continued. “Tuning this genomic machinery in different species has led to the diversity of traits we see in living mammals today.”

Murphy shared that the mammal phylogeny completed by Foley is critical to the goals of Project Zoonomia, 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 is 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 main impetus for compiling this large 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 the evolutionary history of mammals.”

Determining which parts of a gene can be manipulated and which parts cannot be changed without impairing gene function is important for human medicine. A recent study on Science Translation Medicine led by one of Murphy and Foley’s colleagues, Texas A&M geneticist Dr. Scott Didot, uses a comparative genomics approach to develop a molecular therapy for Angelman syndrome, a rare, devastating neurogenetic disorder triggered by loss of maternal function. UBE3A genes in the brain.

Didot’s team took advantage of the same evolutionary constraint measures identified by Project Zoonomia and applied them to identify previously unknown important genetic targets that could be used to salvage expression. UBE3A in human neurons.

Murphy said expanding the ability to compare mammalian genomes using the largest dataset in history would help develop more cures and treatments for diseases of other species that are rooted in genetics, including cats and dogs.

“For example, cats have physiological adaptations that are rooted in unique mutations that allow them to eat a high-fat, high-protein diet that is extremely unhealthy for humans,” explains Murphy. “One of the beautiful aspects of Zoonomia’s 241-species alignment is that we can choose any species (not just humans) as a reference and determine which parts of the species’ genome are free to change and which are intolerant of change. In the case of cats, for example, we may be able to help identify genetic adaptations in that species that could lead to targeted therapy for cardiovascular disease in humans.”

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

“It’s trickle-down genomics,” explains Foley. “One of the most satisfying things for me working as part of a wider project is seeing how many different research projects have improved by including our phylogeny in their analysis. This includes studies from the conservation genomics of endangered species to those looking at the evolution of complex human traits.

Foley said it was meaningful and useful to definitively answer highly debated questions about the timing of mammals’ origins and to come up with an expanded phylogeny that laid the foundations for the next several generations of researchers.

“Going forward, this massive genome alignment and historical record of the evolution of the mammalian genome will form the basis of everything that everyone will do when they ask comparative questions in mammals,” he said. “It is very cool.”

By Rachel Knight, Texas A&M University School of Veterinary Medicine & Biomedical Sciences

###