Major primate genome sequencing studies reveal new insight into evolution, biodiversity and key applications for human health
HOUSTON – (June 1, 2023) – A new investigation led by researchers at Baylor College of Medicine’s Human Genome Sequencing Center, the Institute of Evolutionary Biology and Pompeu Fabra University in Barcelona, Spain, and Illumina, Inc. analyzed the genomes of 233 nonhuman primate species and revealed key features of primate evolution, human disease and biodiversity conservation. The findings are published in a series of studies in a special issue of the journal Science.
The Primate Genome Project generated the most complete catalog of genomic information for primates to date, covering nearly half of all existing primate species on Earth. Researchers from 24 countries compared the genomes of 809 individual primates from 233 species and identified 4.3 million common missense mutations. The resulting studies uncovered DNA sequence variants and developed phylogenies for primate species that will provide new data on primate and human evolution, as well as primate biodiversity. In addition, researchers used primate genomic data to identify new insights into the genetic causes of human disease and developed an algorithm that will help predict pathogenic variants in humans.
“The simultaneous publication of this broad array of papers on primate genomics demonstrates the value and the power of comparative genetics,” said Dr. Jeffrey Rogers, lead investigator and associate professor at the Human Genome Sequencing Center at Baylor. “When we investigate the genomics of nonhuman primates, we not only learn about these species, which is important and timely, but we can also place human genetics into its proper comparative context, which provides new insights into human health and human evolution.”
“Primates have a great genetic diversity that increases between the different geographical regions and taxonomies,” said Dr. Tomàs Marquès-Bonet, lead investigator from Pompeu Fabra. “The study of this diversity is crucial for human evolutionary studies, human disease and for their future conservation.”
“Our studies show which species are in most dire need of conservation efforts and can help identify the most effective strategies for preserving these species,” said Dr. Lukas Kuderna, lead investigator from the Institute of Evolutionary Biology.
Interspecies gene flow in baboons may shed light on human evolution
One of the consortium studies focused on hybridization of genetically distinct lineages in baboons. Researchers used whole genome sequence data from 225 baboons representing multiple populations to identify several new geographic sites of gene flow between populations. They found that yellow baboons (P. cynocephalus) from western Tanzania are the first nonhuman primate shown to have received genetic input from three distinct lineages. The evolutionary dynamics of baboon populations suggest that other early hominins may display similar complexity.
“These results suggest that the population genetic structure and history of introgression among baboon lineages is more complex than was previously thought, and that shows that the baboons are a good model for the evolution of humans, Neanderthals and Denisovans,” Rogers said.
Using primate mutations to predict risk of human disease
One of the consortium studies with key implications for human disease focused on determining clinical relevance of genetic variants. Out of the 4.3 million missense mutations identified in primates in this study, researchers found that 6% can be considered likely benign in human disease because their abundant frequency in primate populations does not appear to have a negative effect. Meanwhile, in the other 94%, researchers used the PrimateAI-3D deep learning algorithm, an artificial intelligence algorithm developed by the team at Illumina, to predict variant pathogenicity in human disease.
“We discovered that if a ‘rare’ mutation cannot be found in the primate genome, it is very likely to cause a human disease,” said Dr. Kyle Farh, lead investigator from Illumina. “In addition, some of these rare mutations can cause, by themselves, some diseases considered polygenic.”
The new genomic catalog outlined in this series of studies has halved the number of genomic innovations that were believed to be exclusively human. This observation facilitates the identification of those mutations not shared with primates that consequently may be unique to human evolution and the characteristics that make us human.
“These studies bring comparative genomics to new heights, and we can predict the impact on both understanding of human biology and on practical clinical diagnostic issues,” said Dr. Richard Gibbs, founding director of the Human Genome Sequencing Center and Wofford Cain Chair and Professor of Molecular and Human Genetics at Baylor.
Other Baylor contributors to this work include R. Alan Harris, Muthuswamy Raveendran, Marie-Claude Gingras, Sejal Salvi and Harshavardhan Doddapaneni. For a full list of authors and funding for this work, see the publications.
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JOURNAL
Science
ARTICLE TITLE
A global catalog of whole-genome diversity from 233 primate species
ARTICLE PUBLICATION DATE
2-Jun-2023
The Primate Genome Project unlocks hidden secrets of primate evolution
Comparative genomic analyses of 50 primate genomes reveal crucial genetic mechanisms of primate speciation, phenotypic adaptability, and social system evolution
Peer-Reviewed PublicationIMAGE: FIGURE 1. GENOMIC PHYLOGENY OF PRIMATES. CREDIT: DONG-DONG WU. view more
CREDIT: CREDIT: DONG-DONG WU.
Co-led by Guojie Zhang from Centre for Evolutionary & Organismal Biology at Zhejiang University, Dong-Dong Wu at Kunming Institute of Zoology, Xiao-Guang Qi at Northwest University, Li Yu at Yunnan University, Mikkel Heide Schierup at Aarhus University, and Yang Zhou at BGI-Research, the Primate Genome Consortium reported a series of publications from its first phase program which includes high quality reference genomes from 50 primate species of which 27 were sequenced for the first time. These studies provide new insights on the speciation process, genomic diversity, social evolution, sex chromosomes, and the evolution of the brain and other biological traits.
Large-scale phylogenomic studies reveal the genetic mechanisms underlying the evolutionary history and phenotypic innovations in primates
The comparative analysis of primate genomes within a phylogenetic context is crucial for understanding the evolution of the human genetic architecture and the inter-species genomic differences associated with primate diversification. Previous studies of primate genomes have focused mainly on primate species closely related to humans and were constrained by the lack of broader phylogenetic coverage.
“Although there are more than 500 primate species worldwide, currently, only 23 representative non-human primates species have had their genomes published, leaving 72% of genera remain unsequenced, which creates significant knowledge gaps in understanding their evolutionary history” Dong-Dong Wu states.
To address this gap, they performed high-quality genome sequencing using long-read sequencing technologies on 27 primate species, including basal lineages that had not been fully sequenced before. Combining this with previously published primate genomes, the project conducted phylogenomic studies of 50 primate species representing 38 genera and 14 families to gain new insights into their genomic and phenotypic evolution.
“Based on full genome data, we have generated a highly resolved phylogeny and estimated the emergence of crown Primates between 64.95 and 68.29 million years ago overlapping the Cretaceous/Tertiary boundary”, Dong-Dong Wu states.
The study reported detailed genomic rearrangements across primate lineages and identified thousands of candidate genes that have underwent adaptive natural selection at different ancestral branches of the phylogeny. This includes genes that are important for the development of the nervous, skeletal, digestive, and sensory systems, all of which are likely to have contributed to evolutionary innovations and adaptations of primates.
“It is surprising to see that so many genomic changes involving brain-related genes occurred in the common ancestor of the Simian group which includes New-world monkey, Old-world monkey, and great apes”, states Guojie Zhang, “These genomic innovations evolving deep in time at this ancestral node might have paved the way for the further evolution of human unique traits”.
Pervasive incomplete lineage sorting illuminates speciation and selection in primates
Although it has been well-recognized that chimpanzees and bonobos are the most closely related species to humans, 15% of our genome is closer to another great ape, the gorilla. This is primarily due to the special evolutionary event called incomplete-lineage sorting (ILS), where the ancestral genetic polymorphism randomly sorts into the descendent species. The study investigated the speciation events during the primate evolution and found ILS occurred frequently in all 29 major ancestral nodes across primates with some nodes having over 50% of genome affected by ILS.
"The genetic diversification process does not follow a bifurcation tree-like topology as we normally know for speciation process, it is more like a complicated net“, Guojie Zhang said. ”It is important to investigate the evolutionary process of each individual gene, which could also affect the evolution of phenotypes across species”.
Incomplete lineage sorting (ILS) exhibits extensive variation along the genome, primarily driven by recombination. “We observed that ILS is reduced more on the X chromosome than autosomes compared to what would be expected under neutral evolution, suggesting a higher impact of natural selection on the X chromosome during primate evolution”, Mikkel Heide Schierup states.
The study exploits ILS to perform molecular dating of speciation events solely based on genome data, without fossil calibration, and found the new dating results were highly consistent with the dating with the fossil record. “This suggests that molecular dating provides an accurate estimate of speciation time even without the fossil records”, says the first author of this paper, Iker Rivas-González.
Hybridization into species events
Hybridization is increasingly recognized as an important evolutionary force for generating species and phenotypic diversity in plants and animals. This is especially common in lineages that can tolerate whole genome duplication and increased levels of ploidy. However, speciation by hybridization has been rarely reported in mammals.
Utilizing full genome data, the team discovered that the gray snub-nosed monkey Rhinopithecus brelichi was a descendent species from the hybridization between the morphologically differentiated species, the golden snub-nosed monkey R. roxellana and the common ancestor of black-white snub-nosed monkey R. bieti and the black snub- nosed monkey R. strykeri.
“To our knowledge, this is the first time that a hybrid speciation event is recorded in primates”, stated by Li Yu.
This study further identifies key genes in R. brelichi that derived from each parental lineages which may have contributed to the mosaic coat coloration in this species, and likely promoted premating reproductive isolation of the hybrid species from the parental lineages.
Multidisciplinary intersection reveals the genetic mechanisms of social complexity in Asian langurs
Primates have very diverse social systems, however the biological mechanisms underlying social evolution remain poorly known. The classical socioecological model hypothesized that the diversity of social systems evolved as a response to the environmental changes.
The study used Asian colobine monkeys as model system, as this group of species underwent a staged social evolution process from a one-male, multi-female unit to complex multi-level social forms. They have re-constructed the speciation process of this group using the full genome data and found a strong correlation between the environmental temperature and group size of the species. The primate species living in colder environments tend to live in larger groups. The ancient ice ages drove the social evolution of these primates, promoting the aggregation of spreading northern odd-nosed monkey species into nested multi-level social forms.
During this transition, odd-nosed monkeys exhibited positive selection in many genes related to cold adaptation and the nervous system. “The snub-nosed monkeys seem to have a longer mother-infant bond, which probably increased infant survival in cold environments, The DA/OXT receptors are important neurohormones in mediating social bonding. This signal pathway has been enhanced in odd-nosed monkey and promoted the social affiliation, cohesion and cooperation among adults of this species” Xiao-guang Qi states.
Figure 3. Gray snub-nosed monkey (Rhinopithecus brelichi). Credit: Gui-Yun Li
CREDIT
Credit: Gui-Yun Li
Figure 4 The hybrid origin of gray snub-nosed monkey. Credit: Li Yu
CREDIT
Credit: Li Yu
Figure 4. Cold promotes the social evolution of the Asian langurs. Credit: Xiao-Guang Qi.
CREDIT
Credit: Xiao-Guang Qi.
Reference articles:
Shao Y, Zhou L, Li F, et al. 2023. Phylogenomic analyses provide insights into primate evolution. Science. https://doi.org/10.1126/science.abn6919
Rivas-González I, Rousselle M, Li F, et al. 2023. Pervasive incomplete lineage sorting illuminates speciation and selection in primates. Science. https://doi.org/10.1126/science.abn4409
Wu H, Wang Z, Zhang Y, et al. 2023. Hybrid origin of a primate, the gray snub-nosed monkey. Science. https://doi.org/10.1126/science.abl4997
Qi X-G, Wu J, Zhao L, et al. 2023. Adaptations to a cold climate promoted social evolution in Asian colobine primates. Science. https://doi.org/10.1126/science.abl8621
Gao H, Hamp T, et al. 2023. The landscape of tolerated genetic variation in humans and primates. Science. https://doi.org/10.1126/science.abn8197
Kuderna L, Gao H, et al. 2023. A global catalog of whole-genome diversity from 233 primate species. Science. https://doi.org/10.1126/science.abn7829
Sørensen E, Harris R, et al. 2023. Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboon. Science. https://doi.org/10.1126/science.abn8153
Fuziev P, McRae J, et al. 2023. Rare penetrant mutations confer severe risk of common diseases. Science. https://doi.org/10.1126/science.abo1131
Zhang B-L, Chen W, et al. 2023. Comparative genomics reveals the hybrid origin of a macaque group. Science Advances. https://doi.org/10.1126/sciadv.add3580
Bi X-P, Zhou L, et al. 2023. Lineage-specific accelerated sequences underlying primate evolution. Science Advances. https://doi.org/10.1126/sciadv.adc9507
Zhou Y, Zhan X-Y, et al. 2023. Eighty million years of rapid evolution of the primate Y chromosomes. Nature Ecology & Evolution. https://doi.org/10.1038/s41559-022-01974-x
For further information and inquiries, please contact:
Guojie Zhang
Contact at Zhejiang University
Dong-Dong Wu
Contact at Kunming Institute of Zoology
Xiao-Guang Qi
Contact at Northwest University
Li Yu
Contact at Yunnan University
Mikkel Heide Schierup
Contact at Aarhus University
Yang Zhou
Contact at BGI-research
JOURNAL
Science
SUBJECT OF RESEARCH
Animals
ARTICLE PUBLICATION DATE
1-Jun-2023
Primates’ DNA highlights applications
for human health
The genomes of 233 primate species reveal key features of primate evolution, human disease and biodiversity conservation
Peer-Reviewed PublicationIMAGE: PRIMATES PHYLOGENETIC TREE. view more
CREDIT: CREDIT: LUKAS KUDERNA
A new investigation led by Tomàs Marquès-Bonet, an ICREA researcher at the IBE (CSIC-UPF) and a professor of Genetics at the Department of Medicine and Life Sciences (MELIS) at Pompeu Fabra University (UPF), Kyle Farh (Illumina), and Jeffrey Rogers (Baylor College of Medicine), combines the genome sequencing of over 800 individuals from 233 primate species, covering nearly half of all existing primate species on Earth, through the study of fossil remains, multiplying by four the number of primate genomes available to date. The study provides new information about primates’ genetic diversity and phylogeny, which is important for understanding and conserving the biodiversity of the closest species to our own.
By comparing the genomes of 809 nonhuman primate individuals from 233 species to the human genome, the research has identified 4.3 million common missense mutations that affect the composition of amino acids and can alter the function of proteins, leading to many human diseases.
Rare missense mutations can raise the risk of disease
One of the limitations of human and clinical genetics is the current inability to detect, among hundreds of thousands of mutations, the ones that cause diseases. Currently, the genetic causes of many common diseases, such as diabetes and heart disease, are unknown, due either to the lack of genetic information or to the large number of genetic factors involved. Some diseases are thought to originate when a set of genetic variations or mutations with a “mild” effect act together to cause a disease of polygenic origin, like diabetes or cancer.
“6% of the 4.3 million missense mutations identified are abundant in primates and are therefore considered “potentially benign” in human disease, given that their presence is tolerated in these animals”, states Kyle Farh, vice president of Artificial Intelligence at Illumina.
The identification of disease-causing mutations has been achieved thanks to the PrimateAI-3D deep learning algorithm. PrimateAI-3D is an artificial intelligence (AI) algorithm developed by Illumina, the world’s leading company in DNA sequencing, and is a kind of ChatGPT for genetics that uses genome sequences instead of human language.
New insights into primate evolution and human uniqueness
The publication of this project includes the most complete catalogue of primate genomic information produced so far, covering nearly half of all existing primate species on Earth. It contains information of primates from Asia, America, Africa, and Madagascar.
According to Tomàs Marquès-Bonet, "Humans are primates. The study of hundreds of nonhuman primate genomes, given their phylogenetic position, is very valuable for human evolutionary studies, to better understand the human genome and the bases of our singularity, including the bases of human diseases, and for their future conservation".
These studies have also indicated that the genetics of primates does not always match their taxonomy. We found several cases in which relationships among primate species are best described as complex and network-like rather than simple branching trees.
Another study delves deeper into the evolution of baboon species, a large and diverse group of monkeys, showing that there have been several episodes of hybridization and gene flow among species that were not previously recognized. In addition, we found that yellow baboons from western Tanzania are the first nonhuman primate to have received genetic input from three different lineages. “These results suggest that the population genetic structure and history of introgression among baboon lineages is more complex than was previously thought, and that shows that the baboons are a good model for the evolution of humans, Neanderthals and Denisovans”, says Jeffrey Rogers, an associate professor at the Human Genome Sequencing Center and Dept. of Molecular and Human Genetics at Baylor College of Medicine, who co-led this study.
“Our studies provide clues as to which species are in most dire need of conservation efforts, and could help to identify the most effective strategies to preserve them.”, Lukas Kuderna, first author of one of the studies, asserts.
Lastly, the new genomic catalogue has halved the number of genomic innovations that were believed to be exclusively human. This observation facilitates the identification of mutations that are not shared with primates that may consequently be unique to human evolution and the characteristics that make us human.
CREDIT
Credit: Rebecca Still
CREDIT
Credit: Jan Dungel
CREDIT
Credit: Marcelo Santana
CREDIT
Credit: Marcelo Santana.
Guinea baboons (Papio papio) at Niokolo Koba National Park, Senegal.
CREDIT
Credit: Sascha Knauf
CREDIT
Credit: Sascha Knauf
JOURNAL
Science
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
Animal tissue samples
ARTICLE TITLE
A global catalog of whole-genome diversity from 233 primate species
ARTICLE PUBLICATION DATE
1-Jun-2023
COI STATEMENT
LFKK, HG, JGS, and KF are employees of Illumina Inc. as of the submission of this manuscript
Primate Genome Special Issue
Reports and ProceedingsGiven primates are threatened, in many cases, by factors including climate change, habitat loss, and illegal trading and hunting, the need for a more complete understanding of primate genetic diversity is urgent. Characterizing primate variation not only allows us to better understand and conserve these species in the wild, but it also helps us to better understand ourselves.
In a special issue of Science, including two related studies from Science Advances, ten papers provide new insights into primate genomes, far exceeding past genomic analyses of primate species. In one study – results from which provide the foundation for several additional studies in the special issue – Lukas Kuderna and team present whole genome data from 233 primate species representing 86% of the primate genera and all 16 families. They used this dataset to estimate the human-chimpanzee divergence as between 9.0 and 6.9 Ma – slightly older than other recent analyses. The authors also explored the association between genomic variation and variables including climate and sociality. Kuderna et al. further studied whether genetic diversity estimates are correlated with extinction risk in primates, a subject of previous debate. “Despite our broad sampling,” the authors write, “we find no global relationship between numerically coded International Union for Conservation of Nature extinction risk categories and estimated heterozygosity.” Finally, the authors used the data to generate a better picture of the mutations that arose in the human lineage and have not emerged elsewhere in primates.
Despite the importance of nonhuman primates, reference genomes have been sequenced in <10% of species, which both impedes research and hampers conservation efforts. Yong Shao and colleagues, in another study in the special issue, present high-quality reference genomes for 27 primate species, adding to available resources. Of particular interest, they report a previously unreported increase in the rate of genomic change in the Simiiformes common ancestor that may have played a role in the later diversification of Simiiformes and the evolution of humans.
A study by Iker Rivas-González and team addresses questions around the process of speciation among populations, focusing specifically on the way some regions of the genome will not show evidence of difference for a long time after ecological speciation has occurred. This process is called incomplete lineage sorting. By accounting for incomplete lineage sorting across primates, Rivas-González et al. were able to produce a primate phylogeny that agrees with fossil estimates, unlike past attempts.
A study by Hong Wu and colleagues focuses on hybridization in mammalian evolution, the role for which is rarely examined. The authors studied the genome sequences from a group of monkey species in the Rhinopithecus genus and found clear evidence that the gray snub nosed monkey is derived from hybridization between the golden snub nosed monkey and the ancestor of two extant Rhinopithecus species. Further, they report the unusual coat color seen in the gray snub nose is due to this mixing. One group of species that has been identified as having a history of hybridization is that containing the genus Papio, the baboons. Erik Sørensen and colleagues used whole genome sequencing to reveal the evolutionary history of overlapping baboon species and found evidence of repeated admixture. “We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages,” they write. Also focused on hybridization in primates, Bao-Lin Zhang and team, in Science Advances, compared reference genomes of 12 macaque species that together cover all the known macaque groups. Their comparative phylogenomic analysis uncovered an ancient hybrid origin of a macaque lineage. “Our study provides both a strategy and a pipeline of genome analyses to identify hybrid speciation, which should pave the way for the identification and exploration of further such events in the future,” write Zhang et al.
JOURNAL
Science
ARTICLE TITLE
Primate genomes
ARTICLE PUBLICATION DATE
2-Jun-2023
