The immense diversity of mammals cannot be understated when looking at animal species through the evolutionary lens. How the mammalian radiation led to such taxonomic diversity at the end of the Cretaceous period, about 66 million years ago, is a question molecular biologists have postulated for quite some time. 

New research from scientists at the European Bioinformatics Institute (EMBL-EBI) and the Cancer Research UK Cambridge Institute (CRUK CI) highlights how evolution rebranded functional genomic elements in order to bring about mammalian diversity. This collaborative effort appears today in Cell in an article entitled “Enhancer Evolution across 20 Mammalian Species”.

Since all mammals share a common ancestry the investigators wanted to know what exactly makes one species different from another, i.e., why a naked mole rat isn’t a whale and what led to their genomic divergence millions of years ago. The scientists believe the answer lies in gene regulation, specifically when and how the genes are controlled.

The EMBL-EBI/CRUK CI teams explored the evolution of gene regulation in 20 mammalian species, 18 placental mammals and 2 marsupials, from 6 diverse orders. Specifically, they were able to compare gene regulation from liver cells of species such as human, naked mole rat, sei whale, macaque, and Tasmanian devil.  

“What we've shown is that evolution repurposes things that exist in all species, to make each species unique,” explains Paul Flicek, D.Sc., head of vertebrate genomics at EMBL-EBI and co-author on the study. “By looking at gene promoters and enhancers in many different mammals, we demonstrated that species-specific enhancers come from ancient DNA — that evolution captures DNA that's been around for a long time, and uses it for gene regulation in specific tissues.”  

Genetic diversity through evolution arises from beneficial mutations that lead to a selective advantage that is propagated along species lines. These mutational changes within the genome can emerge in two main forms, the mutation can occur within the coding region of a gene leading to change in protein sequence or a mutation can appear in the promoter or enhancer region effecting protein expression. The researchers in the current study would argue that evolution often uses both of these strategies synergistically at the same time.

“What inspired this work was a desire to get on top of the mountain, look out and see what is going on in the landscape of molecular evolution across the breadth of mammalian space,” says Duncan Odom, Ph.D., of CRUK CI and Wellcome Trust Sanger Institute. “What's exciting about this study is that we now know we can start to answer questions about the functional genetics of many under-explored species — questions we usually can ask only of humans and mice. We can use tools developed to study humans to understand the biology of all kinds of animals, whether they're blackbirds or elephants, and explore their relationship with one another. This research has given us new insights into mammalian evolution, and proven how powerful these methods can be.”

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