A phylogenetic protein-coding genome-phenome map of complex traits across 224 primate species.

Abstract

Complex traits arise from networks of coding and regulatory loci, making it difficult to resolve their genetic basis. Macroevolutionary studies leverage tens of millions of years of divergence across species to uncover fixed genomic changes invisible to within-species approaches, such as GWAS, offering a complementary framework for generating hypotheses in biomedical research. Here, we present the first phylogenetic protein-coding primate-wide genome-phenome map (P3GMap), spanning 200 curated traits across 224 primate species, which we release through the Primate Genome-Phenome Archive (PGA, https://pgarchive.github.io). Using two complementary approaches, convergent amino acid substitutions and relative evolutionary rates, we linked protein-coding variation to complex phenotypes and identified thousands of candidate gene-trait associations, including lineage-specific signals related to diet, immunity, and lifespan. One sentence summaryCross-species genome-phenome mapping in primates reveals thousands of protein-coding variants linked to the evolution of complex traits.