In research that represents a milestone in the understanding of the human genome, an international scientific consortium has discovered thousands of genetic instructions that distinguish us from other mammals, as well as new regions of the genome where small mutations cause serious diseases.
According to the results of the Zoonomia project, which has compared the genomes of 240 species of mammals, most of the differences between humans and other animals are found, not in the genes, but in the so-called regulatory regions of the genome. These regions control how genes work but are not genes. What distinguishes them is that genes contain instructions for making proteins, while regulatory regions do not make proteins, but rather act as switches that turn genes on or off.
Much of the difference between humans and other mammals is related, as expected, to brain development and function. But, contrary to expectations, many of these differences are deletions, that is, loss of genome fragments, and not genome enrichment that explains greater complexity. In the story of human evolution, less is more.
Thirty-seven scientific teams from seven countries participate in the Zoonomia consortium, which today presents its first results in eleven articles in a special edition of the journal Science. Its objectives include, in addition to advancing in the understanding of the human body and the causes of diseases, investigating the evolution of mammals and contributing to their conservation. Spain is part of the consortium with two teams led by Arcadi Navarro and Tomàs Marquès-Bonet, both from the Institute of Evolutionary Biology (UPF-CSIC) in Barcelona.
The research has been based on comparing the genomes of 240 species of mammals. This has revealed which regions of the genome are the same or very similar between different species and which have more variety.
If they are the same, it means that they have not changed over the more than 180 million years of mammalian evolution. This, in turn, indicates that they are vital regions of the genome where any change dies out. Therefore, these are the regions of the genome where mutations often cause severe disease.
Conversely, regions that exhibit great variety among species are those where variation can be beneficial. These are the regions that evolve the most because the adaptation of animals to changing environments depends on them. These regions regulate traits such as smell, immunity, or skin development.
“The results show how the evolutionary perspective helps to better understand human health and diseasesâ€, states Arcadi Navarro. “Beyond the results presented today, the Zoonomia project provides a huge amount of data that will be studied for years.”
Until now, studies of the genomes of individual species have mainly clarified the role of specific genes, since they are the ones that produce the previously identified proteins. Comparing genomes of different species brings to the fore the role of gene-free regions of the genome, which also play a determining role in mammalian biology and human health.
The Zoonomia project was born from the initiative of the Swedish researchers Kerstin Linblad-Toh (of Uppsala University) and Elinor Karlsson (of the Broad Institute in Boston, USA), who in the middle of the last decade assembled the international consortium that the investigation has been carried out. In addition to the United States, Sweden and Spain, teams from the United Kingdom, Ireland, Germany and Canada have participated.
According to Science in an editorial article, “the Zoonomia project marks the beginning of a new era in which the joint production of genomes of hundreds of species will open the door to new ways of understanding mammals, their evolution and ourselves.”
