Structural Variation in Great Ape Genomes

Abstract

Structural variation within and between Great Ape genomes affects more nucleotides than single‐base variation, yet its extent and phenotypic consequences are much less well understood. The most‐studied structural variants are copy number variations (CNVs) which can be generated by several different mechanisms including non‐allelic homologous recombination, non‐homologous end‐joining and deoxyribonucleic acid (DNA) replication‐related fork stalling and template switching. CNVs are closely related to segmental duplications (SDs): SDs can stimulate the formation of CNVs and themselves started out as CNVs, but became fixed in a species. Structural variation can be neutral but has also influenced our phenotypic evolution, for example our susceptibility to disease and our ability to digest certain types of food. Our understanding of the extent of structural variation is increasing rapidly, but it will be much more difficult to understand its phenotypic consequences. Key concepts Structural variation includes balanced variants such as inversions and translocations, and unbalanced ones such as duplications and deletions (copy number variations or CNVs). Structural variants can arise by several mechanisms, including nonallelic homologous recombination (NAHR), nonhomologous end‐joining (NHEJ) and DNA replication‐based fork stalling and template switching (FoSTeS). CNV is closely linked to segmental duplication, but is not exactly the same. Segmental duplications can stimulate CNV formation by NAHR, and themselves arise from CNVs that have become fixed. Segmental duplications did not appear uniformly during the evolution of the Great Ape species, but rather during a burst of activity around the time of the divergence of gorilla from the human/chimpanzee ancestor. Duplicated genes play a critical role in the evolution of a genome as they act as ‘spare parts’ than can evolve to perform new or more specialized functions. Effects of structural variation on gene expression can be identified but only a few examples of the consequences for species biology have been documented. CCL3L1 copy number varies within humans and has been reported to influence HIV susceptibility. It has been reported to differ in copy number between humans and chimpanzees as well, although other research shows no species difference, illustrating the technical complications associated with such analyses. Humans have more copies of the amylase gene AMY1 than chimpanzees and so are better able to digest starch, which forms a larger part of their diet. Chimpanzees have deleted several inflammatory‐response genes ( APOL1 , APOL4 , CARD18 , IL1F7 and IL1F8 ) and are thus likely to differ in this pathway, but the specific evolutionary force that has driven this change, if any, is unknown.