Data from: Geographic distribution and adaptive significance of genomic structural variants: an anthropological genetics perspective

Anthropological geneticists have successfully used single nucleotide and
short tandem repeat variations across human genomes to reconstruct human
history. These markers have also been used extensively to identify
adaptive and phenotypic variation. The recent advent of high-throughput
genomic technologies revealed an overlooked type of genomic variation,
namely structural variants (SVs). In fact, some SVs may contribute to
human adaptation in substantial and previously unexplored ways. SVs
include deletions, insertions, duplications, inversions and translocations
of genomic segments that vary among individuals from the same species. SVs
are much less numerous than single nucleotide variants, but account for at
least seven times more variable base pairs than do single nucleotide
variants when two human genomes are compared. Moreover, recent studies
have shown that SVs have higher mutation rates than single nucleotide
variants when the affected base pairs are considered, especially in
certain parts of the genome. The null hypothesis for the evolution of SVs,
like single nucleotide variants, is neutrality. Hence, drift is the
primary force that shapes the current allelic distribution of most SVs.
However, due to their size, a larger proportion of SVs appear to evolve
under non-neutral forces (mostly purifying selection) than single
nucleotide variants. In fact, as exemplified by several groundbreaking
studies, SVs contribute to anthropologically relevant phenotypic variation
and local adaption among humans. In this review, we argue that with the
advent of affordable genomic technologies, anthropological scrutiny of
genomic structural variation emerges as a fertile area of inquiry to
better understand human phenotypic variation. To motivate potential
studies, we discuss scenarios through which SVs affect phenotypic
variation among humans within an anthropological context. We further
provide a methodological workflow in which we analyzed 1000 Genomes
deletion variants and identified 16 exonic deletions that are specific to
the African continent. We analyzed two of these deletion variants
affecting the keratin-associated protein (KAP) cluster in a locus-specific
manner. Our analysis revealed that these deletions may indeed affect
phenotype and likely evolved under geography-specific positive selection.
We outline all the major software and datasets for these analyses and also
provide the basic R and perl codes we used for this example workflow
analysis. Overall, we hope that this review will encourage and facilitate
incorporation of genomic structural variation in anthropological research
programs.