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 mammal species. The results show how the genomes of humans and other mammals have evolved over the past 100 million years and which regions have changed or been conserved for millions of years. They also provide new insights into which genetic changes have led to unusual characteristics in different species and which mutations are involved in the development of diseases.
Our genome is made up of billions of base pairs. Only a tiny fraction of this is known about the function of each segment of DNA and what changes in the code are associated with harmful effects. The rate at which individual bases and base sequences change over the course of evolution is considered a marker of evolutionary importance. "Bases that are unchanged in all mammals can shape phenotypes that are essential for the health of the organism," explains a research team led by Matthew Christmas from Uppsala University in Sweden. "Bases that evolve rapidly in some species or change only in species that share an adaptive trait can shape phenotypes that support survival in specific niches."
Genomic similarities and differences
Working with research teams from more than 60 institutions worldwide, 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 research teams involved describe the first results of the extensive analyses. "The combination of the eleven articles that we are now publishing in Science provide an enormous amount of information about the function and development of mammalian genomes," says Christmas colleague Kerstin Lindblad-Toh. "We also obtained data that can be used for evolutionary studies and medical research for many years to come."
One focus of the analyzes was to identify sections of the genome that are evolutionarily conserved in as many very different mammals as possible. According to the researchers' hypothesis, these sections most likely have important functions - otherwise they would not have survived up to 100 million years of evolution. In fact, the researchers identified more than 4,500 regions that are nearly identical in 98 percent of the 240 mammal species studied - from bats to whales. According to the analyzes, most of these DNA sections are regulatory elements. These do not contain the building instructions for proteins, but determine 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
Some of these ancient passages are already known to play an important role in our health. For many others, however, the function is still unclear. A sub-study of the project provides first insights into the possible importance of one of these regions. To this end, researchers examined the genomes of people with medulloblastoma, a malignant brain tumor in children. "In patients with medulloblastoma, we found many new mutations at evolutionarily conserved sites," reports Christmas colleague Karin Forsberg-Nilsson. "We hope that the analysis of these mutations will lay the foundation for new diagnoses and therapies."
In another sub-study, research teams went in search of the genomic basis of 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 which mutations drove the evolution of certain traits in these very different mammals," says Christmas. “For example, in hibernating species, we have identified base sequences that are associated with an exceptional capacity for cellular regeneration. This could also help in researching new therapeutics.”
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 the asteroid impact sealed the extinction of the dinosaurs around 65 million years ago, the ancestors of numerous groups of mammals that still exist today roamed the earth. The results are also important for species protection. "Our results can provide important information about whether certain mammals are threatened with extinction - depending on how much variation they have in their genome," explains Lindblad-Toh. "This information can form the basis of how to deal with a species to ensure its survival."
Sources: Matthew Christmas (Uppsala University, Sweden) et al., Science, doi: 10.1126/science.abn3943;
Nicole Foley (Texas A&M University, USA) et al., Science, doi: 10.1126/science.abl8189