A new mammalian tree of life has been created by a pioneering new study led by scientists from the Texas A&M School of Veterinary Medicine and Biomedical Sciences. It provides a definitive answer to the long-standing question of the evolutionary timeline of mammals throughout the last 100 million years.
The research, published in Science, was conducted as part of the Zoonomia Project. This is a global consortium of scientists working to understand the evolutionary history of the human genome within the context of mammalian evolutionary history by analyzing the largest mammalian genomic dataset ever assembled.
The team, 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, focused on the field of phylogeny, which examines 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,” said Foley.
To create the new mammalian tree of life, the researchers performed new types of analyses made possible by the massive scope of the Zoonomia Project, which allowed them to determine when and where mammals diversified and evolved in relation to the K-Pg mass extinction.
Collaborating with researchers at the University of California, Davis; University of California, Riverside; and the American Museum of Natural History, the team concluded that mammals began diversifying before the K-Pg extinction due to continental drifting. This caused the Earth’s land masses to drift apart and come back together over millions of years.
Another pulse of diversification occurred immediately after the extinction event, when mammals had more room, resources, and stability, leading to the rich diversity of mammal lineages we see today.
The research conducted by Murphy and Foley, which was funded by the National Science Foundation, is part of the larger Zoonomia Project led by Elinor Karlsson and Kerstin Lindblad-Toh, of the Broad Institute.
The project 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 elaborated on the diversity among placental mammals, stating, “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 went on to explain that examining shared differences and similarities across mammalian species at a genetic level can help researchers determine the parts of the genome that are critical to regulating the expression of genes.
Murphy emphasized the significance of Foley’s resolved phylogeny of mammals for the goals of the Zoonomia Project. It seeks 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 said. “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.”
The ability to determine which parts of genes can be manipulated without causing harm to their function is crucial for human medicine. This is another big benefit of the new mammalian tree of life.
A recent study published in Science Translational Medicine, led by Texas A&M geneticist Dr. Scott Dindot, utilized the comparative genomics approach to develop a molecular therapy for Angelman syndrome, a rare and devastating neurogenetic disorder caused by the loss of function of the maternal UBE3A gene in the brain.
This breakthrough was made possible by the groundwork laid by Dr. William J. Murphy and Dr. Nicole Foley’s research on mammalian genomes as part of the Zoonomia Project.
Dindot’s team harnessed the measures of evolutionary constraint identified by the Zoonomia Project to pinpoint a crucial but previously unknown genetic target. This can be used to restore the expression of UBE3A in human neurons.
Murphy explained that expanding the ability to compare mammalian genomes using the largest dataset in history will help develop more cures and treatments for ailments rooted in genetics, not just for humans but also for other species such as 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 said.
“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 has played an instrumental role in several subsequent papers that are part of the Zoonomia 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 expressed the significance of definitively answering the heavily debated question about the timing of mammal origins. Producing an expanded phylogeny through the mammalian tree of life lays the foundation for future 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.”
The Zoonomia Project is a groundbreaking international collaborative effort that brings together scientists from around the globe to study the evolutionary history of the human genome within the context of mammalian evolutionary history. By utilizing the largest mammalian genomic dataset ever assembled, the project aims to better understand the genetic basis for traits and diseases in humans and other species.
The project’s name, “Zoonomia,” is derived from the term “zoonomy,” which refers to the scientific arrangement or classification of animals. The Zoonomia Project has two main objectives:
The project compares the genomes of various mammalian species to identify shared differences and similarities. By analyzing these genomic patterns, scientists can gain insights into the parts of the genome that are critical to regulating gene expression. This knowledge can then be applied to understand the genetic basis of remarkable phenotypes. These include specific physical traits or the origins of diseases.
The Zoonomia Project aims to harness the power of comparative genomics as a tool for human medicine and biodiversity conservation. By understanding the evolutionary history of different mammalian genomes, researchers can develop targeted therapies and treatments for various genetic ailments in humans and other species.
Furthermore, the project contributes to conservation efforts by studying the genomics of endangered species and identifying potential genetic factors contributing to their decline. The new mammalian tree of life is a key contributor.
The Zoonomia Project has already made significant advancements, with researchers like Dr. William J. Murphy and Dr. Nicole Foley resolving long-standing debates about the evolutionary timeline of mammals in relation to the extinction of non-avian dinosaurs.
Moreover, the project has played a crucial role in various research studies, including those focused on conservation genomics of endangered species and the evolution of complex human traits.
The Zoonomia Project’s expansive dataset, which includes alignments of 241 diverse mammalian genomes, is expected to serve as the foundation for countless future studies in the field of comparative genomics and mammalian evolution.