2023-04-27 20:00:06
A dog and a cat. A salmon and a brown bear. A crocodile and a sparrow. A cockroach and a white whale. A human and a starfish. All these couples, so different a priori, are related to each other. In reality, they are all linked: they share common ancestors who lived sometime in the last 3.7 billion years, when life arose on planet Earth. Those ancestors passed on their DNA, the recipe by which living things are created, to their descendants. Although, the replicas underwent changes along the way from which other different characteristics arose that, over time, turned their heirs into other different beings. new species. New families. But not everything was lost: an invariable part remained in that genetic material; a part that has allowed scientists to trace the origins of life almost to the beginning.
Now, an international team, in which 150 researchers from 50 institutions around the world have worked, has developed the Zoonomia Project: a database with the complete genomes of 240 different species of mammals that represent 80% of this type of animals among which we include ourselves. A tool with which to compare from an anteater to a zebu, passing through a human, and the genetic changes that have occurred in the last 100 million years.
As a result, this Thursday the magazine ‘Science’ publishes eleven different studies that have been carried out thanks to the Zoonomia Project and that deal with what genes reveal about the ability to hibernate; how the risk of extinction of the species is also written in its genetic material and how it can help its conservation; or the fraction of DNA that we share with all mammals.
The origins of the Zoonomia Project
“The central idea of the project was to develop and use this data to help human geneticists discover which mutations cause disease,” Kerstin Lindblad-Toh, scientific director of vertebrate genomics at the Broad Institute of MIT and Harvard, told a news conference. , who together with Elinor Karlsson, director of the Lindblad-Toah department, are the coordinators and ultimate managers of this project.
The first step in this huge database was taken in 2006, when the genomes of 29 mammals were sequenced. In 2020, the set was expanded to 120. Now, the bet has been doubled, with 240 genomes, another 120 from previously unsequenced mammals. In addition, they have all been lined up, a very computationally demanding task, so that scientists can compare them much more easily. In other words, the Zoonomia Project collects the ‘genetic recipe’ of 240 animals related to us that reflect 110 million years of evolution.
And not only that: they have organized them so that it is easier to find the part in the DNA where it is written, for example, how the whales stayed in the sea or what caused our brains to get bigger. Also, and this is the most interesting part, the secrets of why we develop some diseases to which other animals seem to be immune. However, it is not as easy as opening a book looking for answers.
«The problem is that you have to interpret these data; and that’s where our work comes in,” explains Irene Gallego Romero, an expert in human evolutionary genomics at the University of Melbourne (Australia), who has written an article in this issue of ‘Science’ that puts into perspective five of the eleven of the published studies -referring to the ‘human’ part of the project-, an example of the potential of this new tool. “It is very interesting work because it allows, for example, to follow the evolutionary history not only of an animal, but also of a specific gene that interests you and to follow its sequence in other mammals,” explains Gallego Romero. “And looking at the bases that do not vary from all of them, you can also extract information about the evolution of this group at the molecular level, so the Zoonomia Project certainly has many potential applications.”
One Gene to Rule Them All
Precisely the part of the genes that do not vary is one of the central studies. Led by Matthew Christmas, a researcher at Uppsala University, and Irene Kaplow, a postdoctoral researcher at Carnegie Mellon University, the team found that at least 10 percent of the human genome is highly conserved in other species; that is, we share it with the rest.
The researchers found that these common genes have changed more slowly than the rest of the random changes in the genome and are involved in embryonic development and the regulation of RNA expression (genes that can interfere, for example, with DNA replication, suppressing in turn specific genes). The researchers also identified parts of the genome linked to some rare traits in the mammalian world, such as a larger brain size than other families, a “sharperer” sense of smell, and the ability to hibernate during the winter.
With an eye to preserving biodiversity, the researchers found that mammals with fewer genetic changes in conserved places in DNA are at higher risk of extinction. Karlsson and Lindblad-Toh, who were also involved in the study, say that even having a single reference genome per species could help scientists identify species at risk, since less than 5 percent of all mammalian species have genomes. reference, although more work is needed to develop these methods.
What animal DNA says about human disease
One of the most interesting parts is, without a doubt, the one referring to applications in human health. Taking these common mammalian genes discovered by the previous study, the team led by Patrick Sullivan, director of the Center for Psychiatric Genomics at the University of North Carolina School of Medicine, compared them to genetic variants that scientists have previously linked to diseases such as cancer thanks to other methods. The team found that their findings were consistent, but also revealed more connections between gene variants and their function than the other systems, as well as new genes that might be involved in rare diseases.
“Some highly restricted genes can make proteins that are almost identical in us and in a mouse,” Sullivan explains. “That’s crazy because there’s probably 60 million years of evolution between humans and mice. And yet this protein hasn’t changed, so we infer that this protein is doing something really important.” Other studies published this Thursday point to specific changes in the organization of the human genome or a ‘machine learning’ system that identified regions associated with brain size.
The findings do not end there: another of the articles shows that mammals diversified before the mass extinction of the dinosaurs, 65 million years ago, a theoretical current that has gained weight in recent years, since it was traditionally thought that our ancestors did not flourish until the disappearance of these giants. One of the most curious works is the story revealed by the genes of Balto, the famous sled dog that saved the people of Nome (Alaska) in 1925 by bringing them medicine and food when they were isolated: the dog was a mixed breed, and not a Siberian husky as thought, which influenced its resistance to cold.
“We are very excited about sequencing mammalian species,” Lindblad-Toh said. “And we are excited to see how we and other researchers can work with this data in new ways to understand both genome evolution and human disease.”
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