Biggest ever study of primate genomes has surprises for humanity

The largest ever study of primates has unveiled surprises about humanity and our closest relatives, providing insight into which genes do, and don’t, separate us from other primates. The huge international study has also yielded new data for a wide range of disciplines, including human health, conservation biology and behavioural science.

More than 500 species of primate exist today, including humans, monkeys, apes, lemurs, tarsiers and lorises. Many are threatened by climate change, habitat loss and illegal hunting. Researchers sequenced genomes from nearly half of all primate species, investigating more than 800 genomes from 233 species around the world, representing all 16 families of primate. The work has been published in a series of papers in Science and Science Advances this week^1–10.

“The more we understand about primate genomics, the more we’ll understand about human genomics,” says primatologist Alison Behie at the Australian National University in Canberra. “There’s a potential there to do a lot more really interesting work as they grow that sample size to bring in more species.”

Huge expansion

Five years ago, scientists had sequenced genomes from less than 10% of primate species, says one of the project leaders, Dong-Dong Wu, an evolutionary biologist at the Chinese Academy of Sciences in Kunming.

The effort started after a team headed by Kyle Farh at sequencing company Illumina, based in San Diego, California, developed a way to estimate whether mutations in the human genome would cause disease by looking for the same mutations in great apes¹¹. The work relied on ape genomes sequenced by Tomàs Marquès Bonet, a comparative genomics researcher at the University of Pompeu Fabra in Barcelona, Spain, and his colleagues, and demonstrated the power of looking beyond human genomes to investigate human diseases.

“Kyle called me one day, and essentially, he was asking if I had more genomes in the queue for sequencing,” says Marquès Bonet. The resulting project quickly attracted researchers from 24 countries who were keen to contribute samples and carry out sequencing. “There was an opportunity for conservation, evolution and understanding the human genome,” says Marquès Bonet.

“I am particularly proud of primatologists in Brazil and in India,” he says, because these hotspots for primate biodiversity were previously under-represented in genetic studies. “This is really a Herculean effort,” he says.

Sequencing is continuing. “It is not the end of this project, it is just the beginning,” says Wu. However, Marquès Bonet says tracking down samples from species that haven’t already been sequenced is becoming harder. “We are reaching a plateau,” he says. “Going from 233 to 300 is becoming extremely difficult.”

Human insights

The primate resource promises to help researchers improve their understanding of human biology and disease. In one study by Marquès Bonet and others, the genomes of the 233 primate species were used to classify 4.3 million common gene variants present in the human genome². By assessing how common those variants were across species, the researchers were able to infer that around 98.7% of the variants they checked are probably benign in humans. This information could be used to help identify disease-causing mutations in people who have had their whole genome or their exome — the protein-coding portion of the genome — sequenced.

In another study, Wu and his colleagues compared the genomes of 50 species to map how the primate family tree evolved³. They identified thousands of genetic sequences that became dominant over evolutionary time in various branches of the tree. For instance, genes involved in brain development arose in the common ancestors of humans, apes and new world monkeys, and set the stage for the rapid evolution of large brains in humans. “Brain expansion began a long time ago,” says Wu.

Meanwhile, a large cache of gene variants thought to be unique to humans, because they are found in Homo sapiens but not in the archaic human relatives called Neanderthals and Denisovans, has turned out to be widespread across primates¹. Almost two-thirds of the variants thought to be solely human were present in at least one other primate species, and more than half were found in two or more.

Genetics of social structure

An ambition of behavioural sciences is to identify genetic mechanisms that explain specific behaviours. One of the studies has drawn that link⁴. Xiao-Guang Qi, a behavioural ecologist at Northwest University in Xi’an, China, says that the five species of snub-nosed monkey are among only a handful of primates — including humans — that form complex multilevel societies in which large troops are composed of smaller family units. Two of the five — the golden snub-nosed monkey (Rhinopithecus roxellana) and the black-and-white snub-nosed monkey (Rhinopithecus bieti) — live in larger groups in cold, high-altitude environments.

By comparing the genomes of the social snub-nosed monkeys with genomes from less-social related monkeys, known as odd-nosed monkeys, and with those of more distant primate relatives, Qi and his colleagues identified genes that seem to be connected with the formation of large multilevel societies. The group found that changes in climate more than six million years ago drove the monkeys’ social structure to shift from small groups with one male and a few females to complex societies with multiple males and females.

“It’s not the present environment that neatly explains their social organization, it’s what happened in the past that’s probably equally important or even more important,” says co-author Cyril Grueter, an evolutionary anthropologist at the University of Western Australia in Perth.

Qi says that changes to the brain hormones dopamine and oxytocin were involved. These neurotransmitters are key to forming social bonds and Qi says that colder conditions required closer bonding between females and their young to ensure survival. This led to more bonded monkeys and larger group sizes, he says.

Grueter says the evolutionary origins of other behaviours, such as mating, could also be investigated using this approach.

The analysis of all 233 species’ genomes also has implications for conservation. For example, it shows that genetic diversity within a species does not align with its extinction risk¹. That’s surprising, says Behie, because lower genetic diversity, which can result from inbreeding when population size diminishes, is widely considered a sign that a species is at risk of extinction. The finding suggests that for some threatened species, populations have declined so fast that there hasn’t been time for inbreeding to occur. This points to factors other than inbreeding — such as habitat destruction — being the greater threat to a species’ resilience.