Exploring Mammalian Genetics That Hasn’t Changed

From the bumblebee bat that weighs just a couple of grams, to whales that add up to many tons, the more than 6,000 species of mammals on the planet – humans included – are highly divergent. Over the last 100 million years, they have adapted to almost every environment on Earth.

Now, an international collaboration of scientists in the Zoonomia Project – the world’s largest comparative mammalian genomics resource – has cataloged the diversity in the genomes of 240 mammal species representing more than 80% of mammal families.

Through 11 studies published in the academic journal Science, their findings identify parts of the human genome that have remained unchanged after millions of years of evolution, providing information that can shed light on health and disease in humans.

The work of these scientists also reveals how rare mammalian traits, such as the ability to hibernate, developed. The researchers say these analyzes – and the breadth of questions they answer – show only a fraction of what can be accomplished with these data to understand both genome evolution and disease-promoting problems in the genome. human being.

The Zoonomia project is an international effort in which researchers sequenced a series of mammalian genomes that they then aligned in a massive computational task. Using the alignment, the researchers identified regions of genomes—sometimes just individual DNA letters—that are most conserved, or unchanged, between different mammalian species and over millions of years of evolution, leading them to to hypothesize that these regions were biologically important. These regions—although they do not give rise to proteins—may contain instructions that tell where, when, and how much protein is made. The authors hypothesize that mutations in these regions could play an important role in the origin of numerous diseases or in the distinctive characteristics of mammalian species.

Throughout their analyses, the researchers tested this hypothesis and were able to determine that at least 10% of the human genome is functional, ten times more than the roughly one percent devoted to protein coding. The findings also revealed genetic variants that likely play a causal role in rare and common human diseases, including cancer. In one of the studies, the authors, who investigated patients with medulloblastoma, identified mutations in evolutionarily conserved positions in the human genome that they believe could cause brain tumors to grow faster or resist treatment. The results show how the use of these data and an appropriate approach could facilitate the identification of genetic changes that increase the risk of disease.

Blue whale. (Photo: NOAA)

In other studies, the researchers identified parts of the genome linked to some rare traits in the mammalian world, such as extraordinary brain size, a highly developed sense of smell, and the ability to hibernate during the winter. The researchers found that species with fewer genetic changes in conserved regions of the genome may be particularly susceptible to extinction, information that the researchers say can lay the foundation for how best to manage a species.

Another of the studies shows that mammals had already begun to change and diverge even before Earth was hit by the asteroid that wiped out the dinosaurs approximately 65 million years ago.

A different study examined more than 10,000 human-specific genetic deletions using Zoonomy data and experimental analyses, linking some of them to neuron function.

In other studies, a genetic explanation is revealed for why a famous sled dog from the 1920s named Balto was able to survive the harsh landscape of Alaska; human-specific changes in genome organization are discovered; machine learning is used to identify regions of the genome associated with brain size; the evolution of regulatory sequences in the human genome is described; the DNA sequences that move around the genome are studied; species with historically smaller populations are found to be at higher risk of extinction today, and genes are compared across many mammalian species. (Source: AAAS)