Cienciaes.com: Genetic variation between humans and the rest of the primates. We spoke with Tomás Marqués Bonet.

2023-07-13 17:42:03

Each one of us carries in our cells a copy of our DNA, the molecule of life, an extraordinarily long molecule in which four different units follow one another, called nucleotides, which, like four chemical letters, write the information that makes us human. The genetic code is immensely long, it is said to contain no less than 3 billion letters, although, as our guest, Tomás Marqués Bonet, an ICREA researcher at the Institute of Evolutionary Biology in Barcelona, ​​makes clear, we actually have twice as many, because each of our parents has given us a copy.

There are no two identical genomes, or what is the same, there are no two identical human beings, even identical twin brothers, who come from the same embryonic cell, end up accumulating differences in the code. If we compare, letter by letter, our DNA with that of any other human being, we will discover that in certain places the letters do not correspond, the percentage of these genetic differences is very small, but enough to make us unique.

Since the first human genome was read at the beginning of the century, genetic sequencing technologies have been improving in such a way that the genome of millions of people is now known. But, as Tomás Marqués comments, it is not enough to know the letters of a text, one must know how to interpret the meaning of the message and in that there is still a long way to go.

Of the 3,000 million letters that make up our genome, certain portions, the genes, contain the formula of the proteins. A little less than 20,000 genes are known, but these only represent one percent of the total genome, we know little about the rest.

Of the millions of people whose genomes have been sequenced, it has been possible to extract information about the vast catalog of small genetic differences that distinguish us as individuals within our species. Identifying which of these differences are reflected in our physical appearance, which enhance our abilities or discovering those that are linked to diseases or problems is a difficult challenge to overcome.

To discover these differences, an international team of scientists, led by Tomás Marqués Bonet, has used a novel approach: comparing our genome with that of other primates to discover which genome variants are exclusive to our species and delimit the effects of mutations. Given the short evolutionary distance between humans and non-human primates, our proteins share near-perfect amino acid sequence identity. Therefore, the effects of a protein-altering mutation found in one species are likely to be concordant in the other species.

In order to compare the different genomes, the researchers have carried out a task of selecting different species of primates, extracting and sequencing their DNA. Over five years, the international consortium of scientists has succeeded in extracting the complete genomes of 809 individuals from 233 primate species, roughly half of the known primate species.

Comparison between genomes makes it possible to detect those mutations, present in humans, that also appear in other primate species. Tomás Marqués explains during the interview that if a person suffers from a disease and has a mutation, the fact that it appears in another primate is an indication that said genetic change is not related to the disease. Using this criteria, researchers have reclassified more than 4 million human missense variants of previously unknown consequences as probably benign.

Tomás Marqués Bonet, an ICREA researcher at the Institute of Evolutionary Biology of Barcelona (UPF-CSIC), talks about these and many other things in this new installment of the Hablando con Científicos podcast. I invite you to listen to it.

References:

Gao et al., The landscape of tolerated genetic variation in humans and primates. Science 380, eabn8197 (2023) 2 June 2023

KUDERNA et al. A global catalog of whole-genome diversity from 233 primate species SCIENCE 1 Jun 2023 Vol 380, Issue 6648 pp. 906-913

SØRENSEN et al,.“Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons”:DOI: 10.1126/science.abn8153 SCIENCE 2 Jun 2023 Vol 380, Issue 6648