title: Genes with monoallelic expression contribute disproportionately to genetic diversity in humans.
abstract: An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes uncovers surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit an elevated recombination rate and an increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: variants in these genes tend to be older and are enriched in polymorphisms shared by Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles of MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be the generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity.
authors.affiliation: Dana-Farber Cancer Institute, Boston, USA.|Department of Genetics, Harvard Medical School, Boston, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Savova
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Sung
authors.initials: S
authors.lastname: Chun
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Mashaal
authors.initials: M
authors.lastname: Sohail
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, USA.
authors.forename: Ruth B
authors.initials: RB
authors.lastname: McCole
authors.affiliation: Dana-Farber Cancer Institute, Boston, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Witwicki
authors.affiliation: Dana-Farber Cancer Institute, Boston, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gai
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Tobias L
authors.initials: TL
authors.lastname: Lenz
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, USA.
authors.forename: C-Ting
authors.initials: CT
authors.lastname: Wu
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Shamil R
authors.initials: SR
authors.lastname: Sunyaev
authors.affiliation: Dana-Farber Cancer Institute, Boston, USA.|Department of Genetics, Harvard Medical School, Boston, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Gimelbrant
mesh_terms: D000483:Alleles; D000818:Animals; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D059125:Neanderthals / Q000235:genetics; D002679:Pan troglodytes / Q000235:genetics