Newswise — A fresh study conducted by scientists from Baylor College of Medicine’s Human Genome Sequencing Center, the Institute of Evolutionary Biology, Pompeu Fabra University in Barcelona, Spain, and Illumina, Inc. scrutinized the genetic makeup of 233 nonhuman primate species. Their analysis unveiled significant aspects of primate evolution, human disease, and biodiversity preservation. The results have been published in a set of research papers featured in a special edition of the journal Science.

The Primate Genome Project accomplished the creation of a comprehensive record of genomic data for primates, marking a significant milestone in primate research. This groundbreaking initiative encompassed nearly half of the total primate species found on Earth. Collaborating researchers from 24 nations meticulously compared the genomes of 809 individual primates, representing 233 distinct species. Through this endeavor, they successfully identified 4.3 million common missense mutations. The ensuing investigations unveiled DNA sequence variations and constructed phylogenies, shedding light on primate and human evolution, as well as primate biodiversity. Moreover, the utilization of primate genomic information enabled researchers to gain fresh insights into the genetic origins of human diseases. Additionally, they devised an algorithm capable of predicting pathogenic variants in humans, thereby providing a valuable tool for future research.

Dr. Jeffrey Rogers, the lead investigator and associate professor at Baylor's Human Genome Sequencing Center, expressed the significance and potency of comparative genetics as demonstrated by the simultaneous publication of this diverse collection of primate genomics papers. He emphasized that exploring the genomics of nonhuman primates not only enhances our understanding of these species, which is crucial and relevant in the current times, but also enables us to gain valuable insights into human health and human evolution by placing human genetics within the appropriate comparative framework. This approach unveils new perspectives and contributes to our knowledge in these fields.

Dr. Tomàs Marquès-Bonet, the lead investigator from Pompeu Fabra, highlighted the substantial genetic diversity observed among primates, which intensifies across distinct geographical regions and taxonomic classifications. He emphasized that studying this diversity is of utmost importance for understanding human evolution, investigating human diseases, and effectively preserving these species in the future. By exploring the genetic makeup of primates, we gain valuable insights that contribute to various fields of research and conservation efforts.

According to Dr. Lukas Kuderna, the lead investigator from the Institute of Evolutionary Biology, their studies provide insights into identifying the species that require urgent conservation efforts. Furthermore, their research aids in determining the most efficient strategies to preserve these species effectively. By analyzing the data, conservationists can prioritize their actions and allocate resources to safeguard the most vulnerable species. Dr. Kuderna's findings play a crucial role in guiding conservation initiatives and contribute significantly to the preservation of these species.

Interspecies gene flow in baboons may shed light on human evolution

A consortium study delved into the hybridization patterns of genetically distinct lineages in baboons. By analyzing whole genome sequence data from 225 baboons across various populations, researchers uncovered previously unknown geographic regions where gene flow occurred between these populations. Notably, they discovered that yellow baboons (P. cynocephalus) originating from western Tanzania received genetic contributions from three distinct lineages, making them the first nonhuman primate known to exhibit such complexity. The evolutionary dynamics observed in baboon populations hint at the possibility that other early hominins might display similar intricate genetic patterns.

Dr. Rogers commented that the obtained results indicate a more intricate population genetic structure and history of introgression among baboon lineages than previously believed. This finding highlights baboons as a valuable model for studying the evolution of humans, Neanderthals, and Denisovans. The complexities observed in baboon genetic patterns shed light on the interbreeding dynamics and genetic exchanges that may have occurred among ancient human species. This insight enhances our understanding of the evolutionary history shared between humans and our hominin relatives, providing valuable information about our own genetic heritage.

Using primate mutations to predict risk of human disease

A significant study conducted by the consortium aimed to assess the clinical significance of genetic variants, which has implications for human diseases. Among the 4.3 million missense mutations discovered in primates during this study, researchers determined that approximately 6% can be regarded as likely benign in terms of human disease. This conclusion was drawn based on their prevalent frequency within primate populations, indicating that these variants do not appear to have a detrimental impact. In the remaining 94% of mutations, researchers employed the PrimateAI-3D deep learning algorithm, developed by the team at Illumina, to predict the pathogenicity of these variants in relation to human diseases. By utilizing artificial intelligence, the algorithm aids in assessing the potential impact of these genetic variants on human health and disease.

Dr. Kyle Farh, the lead investigator from Illumina, shared a significant discovery made during the study. He explained that if a mutation classified as "rare" cannot be detected within the primate genome, it is highly likely to be associated with a human disease. This finding underscores the importance of studying the genetic variations in primates to better understand the genetic basis of human diseases. Additionally, Dr. Farh highlighted that certain rare mutations have the potential to cause diseases that were previously considered polygenic, meaning they are influenced by multiple genetic factors. This insight emphasizes the significant role that these rare mutations can play in the development of specific diseases, even when other genetic factors are not involved.

The comprehensive genomic catalog presented in this series of studies has revealed a remarkable finding: it has reduced by half the number of genomic innovations previously thought to be exclusive to humans. This discovery paves the way for identifying mutations that are not shared with other primates, potentially highlighting genetic variations that are unique to human evolution and contribute to the distinct characteristics that define us as humans. By elucidating these distinctive genetic features, we gain valuable insights into the factors that have shaped human evolution and the traits that set us apart from other species.

Dr. Richard Gibbs, the founding director of the Human Genome Sequencing Center and Wofford Cain Chair and Professor of Molecular and Human Genetics at Baylor, expressed his enthusiasm for the studies conducted, noting their significant contributions to the field of comparative genomics. He emphasized that these studies have elevated our understanding of human biology to new heights. Additionally, Dr. Gibbs highlighted the practical implications for clinical diagnostics, indicating that the findings have the potential to impact diagnostic practices in a tangible and beneficial manner. The studies' outcomes hold great promise in advancing our knowledge of human biology and improving clinical approaches for diagnosing and treating various conditions.

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 Link: Science