Genome structural variation in human evolution

There has been an explosion in knowledge of structural variants through analysis of short-read sequencing in large population cohorts. Long-read sequencing technology is dramatically improving our ability to detect and genotype structural variants, particularly in complex repeat-rich regions. Structural variants are important in neurological changes involved in human evolution. Structural variants have mediated population-specific human adaptations to diet and infectious disease exposure. Introgression from archaic hominins has contributed structural variants to modern human populations. Structural variation (SV) is a large difference (typically >100 bp) in the genomic structure of two genomes and includes both copy number variation and variation that does not change copy number of a genomic region, such as an inversion. Improved reference genomes, combined with widespread genome sequencing using short-read sequencing technology, and increasingly using long-read sequencing, have reignited interest in SV. Recent large-scale studies and functional focused analyses have highlighted the role of SV in human evolution. In this review, we highlight human-specific SVs involved in changes in the brain, population-specific SVs that affect response to the environment, including adaptation to diet and infectious diseases, and summarise the contribution of archaic hominin admixture to present-day human SV. Structural variation (SV) is a large difference (typically >100 bp) in the genomic structure of two genomes and includes both copy number variation and variation that does not change copy number of a genomic region, such as an inversion. Improved reference genomes, combined with widespread genome sequencing using short-read sequencing technology, and increasingly using long-read sequencing, have reignited interest in SV. Recent large-scale studies and functional focused analyses have highlighted the role of SV in human evolution. In this review, we highlight human-specific SVs involved in changes in the brain, population-specific SVs that affect response to the environment, including adaptation to diet and infectious diseases, and summarise the contribution of archaic hominin admixture to present-day human SV. acquisition of variants from archaic hominins that have enabled adaptation in new environments. a variant that is correlated with levels of mRNA of a particular gene in a particular tissue or cell type. change in allele frequency from one generation to the next because of random variation in offspring number between different individuals in a finite population. a protein made of two different subunits. a protein made of two identical subunits. two identical alleles that have arisen from a single mutational event. Segments of identity by descent are genomic regions over which a pair of individuals share a haplotype due to inheritance from a recent common ancestor. two identical alleles that have arisen in different mutational events. using the information from the known haplotypes present in a population to infer a genotype at a locus. acquisition of variants from archaic humans. the nonrandom association of alleles at two or more loci. a copy number variant with more than one allele in the population; usually, each allele consists of a variable number of tandem repeats. evolution by retaining juvenile features in the adult, often by slowing or delaying particular developmental processes. a mutational process whereby unequal crossing over during meiosis between similar DNA sequences generates deletions or duplications. Also known as ‘ectopic recombination.’ determining the haplotype of multiple alleles from diploid genotypes. sections of DNA that map to at least two different genomic locations. Originally coined to distinguish shorter interspersed duplications from whole-genome duplications. specific single nucleotides in the genome that differ between members of the same species; for example, in some human genomes, it could be an A, in others a C. essentially synonymous with SNVs but sometimes used to imply a common SNV in a population: An SNP is an SNV that occurs at >1% frequency in a specific population.