New Research Study Combines Genome Sequences Of 233 Primates And Fetches Answers About Humans
In a special issue of the journal Science, studies are presented in which researchers from 24 different countries compared the genomes of over two hundred species of primates. The results constitute the most complete catalog of primate genomic information ever. Researchers at Uppsala University have contributed to the work which, among other things, provides new insights into the genetic causes of human diseases.
The new research study combines genome sequences from over 800 individuals from 233 primate species – nearly half of all extant primate species on Earth – with studies of fossil remains, quadrupling the number of primate genomes available. The study provides new information about primate genetic diversity and phylogeny (hypothesis of relatedness), which is important for understanding and conserving the biodiversity of the species closest to our own.
By comparing the genomes of the more than two hundred species with humans, the researchers have identified 4.3 million common mutations that affect the composition of amino acids and can alter the function of proteins, leading to many human diseases.
Evolutionary tree of primates
The new dataset includes information on primates from Asia, the Americas, Africa and Madagascar. The catalog has enabled the research team to produce an evolutionary tree of primates to improve understanding of their evolutionary history, and it has provided important insights into what makes us human.
– We can learn a lot about the evolutionary path that made us human by studying our closest relatives. Many primate species are threatened with extinction, so understanding how they differ in genetic diversity and the occurrence of harmful mutations is crucial for their future conservation, says Katerina Guschanski, researcher working at Uppsala University and the University of Edinburgh.
These studies have also shown that the genetics of primates does not always agree with their taxonomy. The team found several cases where relationships between primate species do not follow a simple branching tree and are likely the result of gene flow that happened long ago.
– The immense diversity of primates, which can be studied with this unique data set, shows how complex evolution can be. Species can separate and meet again to exchange genes that may be important for their survival, says Axel Jensen, PhD student at Uppsala University who contributed to the study.
Characteristics that make us human
Finally, the new genomic catalog has halved the number of genomic innovations that were considered unique to humans. This observation facilitates the identification of those mutations not shared with other primates that may underlie the traits that make us human.
– We are always very curious about our own species – humans. However, it is important to remember that every species alive today is as unique as humans are. The dataset produced will enable future studies of exactly what makes the non-human primates unique, emphasizes Katerina Guschanski.
Mutations work together in disease
Mutations that lead to changes in the protein that the gene codes for are called missense mutations, and can have a negative impact on health. One of the limitations of human and clinical genetics is the current inability to detect, among hundreds of thousands of such mutations, those that cause disease. Currently, the genetic causes of many common diseases, such as diabetes and heart disease, are unknown, either because of the lack of genetic information or because of the large number of genetic factors involved. Some diseases are thought to arise when a set of genetic variations or mutations with a “mild” effect combine to cause a disease of polygenic origin, such as diabetes or cancer.
“Six percent of the 4.3 million missense mutations identified are common in primates and are therefore considered ‘potentially benign’ in human disease, given that their presence is tolerated in these animals,” said Kyle Farh, Vice President of Artificial Intelligence at the research company Illumina.
Artificial Intelligence
The identification of disease-causing mutations has been accomplished thanks to the deep learning algorithm PrimateAI-3D. PrimateAI-3D is an artificial intelligence algorithm developed by Illumina, a leading company in DNA sequencing, and is a kind of ChatGPT for genetics that uses genome sequence instead of human language.
The research behind the new studies was led by Tomàs Marquès-Bonet, ICREA researcher at IBE (CSIC-UPF) and Professor of Genetics at Pompeu Fabra University (UPF), Kyle Farh (Illumina) and Jeffrey Rogers (Baylor College of Medicine), with contributions from an international team of researchers, including researchers at Uppsala University.