Reading the DNA of 233 primate species illuminates what a person is and how human diseases arise

The last common ancestor of people and chimpanzees roamed the planet about seven million years ago. It may seem like a lot, but it's about the same distance that separates African elephants and Asian elephants, two species so similar that people often call them, simply, elephants. The biologist Tomàs Marquès Bonet works to answer one of the great questions of humanity: what makes us human, what happened in those seven million years so that people are able to walk on the Moon and the rest of primates are still in the branches of the trees. This Thursday has taken a giant step. An international consortium led by Marquès Bonet has read the DNA of 233 primate species, half of all known ones. This monumental genetic information serves to specify what a human being is, but also to illuminate the origin of a multitude of diseases, such as cancer.

A person's genome, their DNA, is a text of more than 3 billion chemical letters, with instructions for each cell to know what to do. "If we sequence the DNA of a sick person, we will find thousands of candidate mutations to be linked to that disease," explains Marquès Bonet, from the Institute of Evolutionary Biology, in Barcelona. The researcher says that, five years ago, the American company Illumina, a world leader in DNA sequencing technology, proposed to coordinate a macroproject to read the genomes of hundreds of primate species, with the aim of developing a genetic catalog that allows identifying which are the specific variants of human diseases. Their results are published Thursday in a special issue of the journal Science.

"We don't know from which creature humans and chimpanzees evolved"

"If you see a mutation in a patient and you also find it in several primate species, discard it, because it is surely not the cause of the disease. If, on the other hand, you find a mutation that only appears in a tumor tissue, and has never been seen in any other primate, that mutation must do something disruptive in the cell and is a perfect candidate to continue pulling the thread, "says Marquès Bonet.

The consortium has analyzed the DNA of more than 800 individuals from 233 species, including those closest to humans – chimpanzees, gorillas and orangutans – and some critically endangered, such as the Sahafary jumping lemur, of which there are only 40 specimens left in the wild in Madagascar. The researchers have used this data to train an algorithm with which to identify mutations associated with diseases. This new artificial intelligence tool has revealed 73% more links between genetic variants and pathologies, according to a study carried out with the UK Biobank, a biomedical data registry of almost half a million volunteers.

Tomàs Marquès Bonet, Alejandro Valenzuela, David Juan, Esther Lizano and Arcadi Navarro, co-authors of the study, at the Institute of Evolutionary Biology, in Barcelona.IBE and UPF

"We have put the algorithm to work with complex diseases, such as diabetes and cancer, where obviously the cause is not a mutation in a gene, but a combination of many things," says Marquès Bonet. "There are common mutations that contribute, as we have seen so far, but, for the first time, we can say that there are rare, rare mutations that have a very large impact on these complex diseases. And we have achieved this with an algorithm trained with primates," says the biologist. Its institute is a joint centre of the Spanish National Research Council (CSIC) and Pompeu Fabra University.

Marquès Bonet explains that, when they started the project five years ago, the genomes of only a couple of dozen primate species had been sequenced. "Jumping from 20 to 233 is a huge increase, which allows us to better filter out what is uniquely human and what is not. Basically, we have halved the candidate mutations to define our species," says the researcher. His team has detected 89 variants in 80 genes that are crucial to explaining what a human being is. Marquès Bonet cites as an example the NOVA1 gene, which acts as an orchestra conductor in the early development of the brain.

16% of the human genome is more like the gorilla genome than the chimpanzee genome

Iker Rivas González, bioinformatics specialist

The paths of chimpanzees and humans forked more than seven million years ago. The group of gorillas left the common path before, about eight million years ago, according to Iker Rivas González, a specialist in bioinformatics at the University of Aarhus (Denmark). "However, about 16% of the genome of humans is more similar to the genome of gorillas than to that of chimpanzees," says Rivas González, who heads one of the eight studies published in the special issue of Science. Rivas González's team studies this phenomenon, which causes parts of the same genome to have different evolutionary histories. His group has detected that there are genes linked to the fur or the immune system that are evolving faster than the rest of the primate genes.

Primatologists around the world look to monkeys and apes for keys to human social evolution. Julia Fischer, from the German Primate Center, studies Guinea baboons, 15-kilo African monkeys with a unique behavior: females choose a male of their liking and no longer mate with any other. The males, meanwhile, wait to be chosen by one or more females and copulate with all of them. The question is to what extent these behaviors are rooted in DNA.

"It's an absolutely fantastic question," says Marquès Bonet. His group participated more than a decade ago in the first sequencing of the genomes of chimpanzees and bonobos. The former form very violent patriarchal groups, while bonobos constitute peaceful matriarchal societies, which use sex to resolve conflicts. "So we look for areas of the genome associated with these behaviors and we do not find them, but that does not mean that they are not there," he acknowledges. The torrent of primate data now opens the door to new discoveries.

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