The genomes of 240 mammalian species were compared

The genome provides information about evolutionary lineage and encodes the basis for disease and health as well as unique traits. In the large-scale research project Zoonomia, international research teams analyzed and compared the complete genomes of 240 mammalian species. The results show how the genomes of humans and other mammals have evolved over the past 100 million years and what regions have changed or been preserved for millions of years. They also provide new insights into the genetic changes that have led to unusual characteristics in different species and the mutations that are involved in the development of diseases.

Our genome consists of billions of base pairs. Only a fraction of this is known about the function of each piece of DNA and what changes in the code are associated with adverse effects. The rate at which individual bases and basic sequences change over the course of development is a sign of evolutionary significance. “Unchanged bases in all mammals can shape phenotypes that are essential to an organism’s health,” explains a research team led by Matthew Christmas of Uppsala University in Sweden. “Rules that evolve rapidly in some species or only change in species that share an adaptive trait can form phenotypes that support survival in specific niches.”

Genomic similarities and differences

Working with research teams from more than 60 institutions around the world, Christmas and his team sequenced, analyzed and compared the genomes of 240 mammalian species as part of the Zoonomia project. Zoonomia thus provides the world’s largest comparative resource for mammalian genomes. In eleven articles in the journal Science, the participating research teams describe the first results of the extensive analyses. “The combination of the eleven articles that we are now publishing in Science provides an enormous amount of information about the function and evolution of mammalian genomes,” says Christmas colleague Kirsten Lindblad-Toh. “We also got data that can be used in developmental studies and medical research for many years to come.”

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The analyzes focused on identifying sections of the genome that are evolutionarily conserved in as many different mammals as possible. According to the researchers’ hypothesis, these departments most likely have important functions – otherwise they would not have survived even 100 million years of evolution. In fact, the researchers identified more than 4,500 nearly identical regions in 98 percent of the 240 mammalian species studied–from bats to whales. According to the analyses, most of these DNA sections are regulatory elements. These do not contain the instructions for building proteins, but do specify how the genome is read. “We estimate that at least 10.7 percent of the human genome is evolutionarily conserved,” the authors said.

Health importance

It is already known that some of these ancient pathways play an important role in our health. However, for many others, the job is still not clear. A sub-study of the project provides the first insights into the potential importance of one of these areas. To this end, the researchers examined the genomes of people with medulloblastoma, a malignant pediatric brain tumor. “In patients with medulloblastoma, we found many new mutations at evolutionarily conserved sites,” says Christmas colleague Karen Forsberg-Nelson. “We hope that analysis of these mutations will lay the groundwork for new diagnoses and treatments.”

In another substudy, the research teams looked for the genetic basis for unusual traits in certain animals, including a keen sense of smell and the ability to hibernate. “It’s exciting that we now have a picture of the mutations that led to the evolution of certain traits in these very different mammals,” says Christmas. “For example, in hibernating species, we have identified key sequences associated with an exceptional capacity for cellular regeneration. This could also help in the search for new therapies.”

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Important for species protection

The analyzes also show that the diversification of mammals began when they were still sharing the planet with dinosaurs. Long before an asteroid impact halted the extinction of the dinosaurs some 65 million years ago, the ancestors of many groups of mammals that still exist today roamed the Earth. The results are also important for protecting species. “Our results can provide important information about whether certain mammals are threatened with extinction – depending on how much variation there is in their genome,” explains Lindblad-Toh. “This information can form the basis of how we treat species to ensure their survival.”

Sources: Matthew Christmas (Uppsala University, Sweden) et al., Science, Available here. doi: 10.1126/science.abn3943;
Nicole Foley (Texas A&M University, USA) et al., Sciences, doi: 10.1126/science.abl8189

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