Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility

Genetic differences that specify unique aspects of human evolution have typically been identified by comparative analyses between the genomes of humans and closely related primates, including more recently the genomes of archaic hominins. Not all regions of the genome, however, are equally amenable to such study. Recurrent copy number variation (CNV) at chromosome 16p11.2 accounts for approximately 1% of cases of autism and is mediated by a complex set of segmental duplications, many of which arose recently during human evolution. Here we reconstruct the evolutionary history of the locus and identify bolA family member 2 (BOLA2) as a gene duplicated exclusively in Homo sapiens. We estimate that a 95-kilobase-pair segment containing BOLA2 duplicated across the critical region approximately 282 thousand years ago (ka), one of the latest among a series of genomic changes that dramatically restructured the locus during hominid evolution. All humans examined carried one or more copies of the duplication, which nearly fixed early in the human lineage—a pattern unlikely to have arisen so rapidly in the absence of selection (P
Paul G. Allen Family Foundation (11631)
Simons Foundation Autism Research Initiative (303241)
Simons Foundation Autism Research Initiative (274424)
United States. National Institutes of Health (2R01HG002385)
United States. National Institutes of Health (TR01 MH095741)
G. Harold and Leila Y. Mathers Foundation
JPB Foundation
Leona M. and Harry B. Helmsley Charitable Trust
National Science Foundation (U.S.) (DGE-1256082)
National Institute of Mental Health (U.S.) (1F30MH105055-01)