Comparative Genomic Analysis Identifies Great-Ape-Specific Structural Variants and Their Evolutionary Relevance

During the origin of great apes about 14 million years ago, a series of phenotypic innovations emerged, such as the increased body size, the enlarged brain volume, the improved cognitive skill, and the diversified diet. Yet, the genomic basis of these evolutionary changes remains unclear. Utilizing the high-quality genome assemblies of great apes (including human), gibbon, and macaque, we conducted comparative genome analyses and identified 15,885 great ape-specific structural variants (GSSVs), including eight coding GSSVs resulting in the creation of novel proteins (e.g., ACAN and CMYA5). Functional annotations of the GSSV-related genes revealed the enrichment of genes involved in development and morphogenesis, especially neurogenesis and neural network formation, suggesting the potential role of GSSVs in shaping the great ape-shared traits. Further dissection of the brain-related GSSVs shows great ape-specific changes of enhancer activities and gene expression in the brain, involving a group of GSSV-regulated genes (such as NOL3) that potentially contribute to the altered brain development and function in great apes. The presented data highlight the evolutionary role of structural variants in the phenotypic innovations during the origin of the great ape lineage.