title: The evolution and functional impact of human deletion variants shared with archaic hominin genomes.
abstract: Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins. However, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. We identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the Human-Neandertal divergence (ancient) and only approximately 9% of which have been introgressed from Neandertals (introgressed). Recurrence, incomplete lineage sorting between human and chimp lineages, and hominid-specific insertions constitute the remaining approximately 4% of allele sharing between humans and archaic hominins. We observed that ancient deletions correspond to more than 13% of all common (>5% allele frequency) deletion variation among modern humans. Our analyses indicate that the genomic landscapes of both ancient and introgressed deletion variants were primarily shaped by purifying selection, eliminating large and exonic variants. We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts. The affected genes are involved in metabolism of external and internal compounds, growth and sperm formation, as well as susceptibility to psoriasis and Crohn's disease. Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection. Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes.
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, NY, US.
authors.forename: Yen-Lung
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Institute of Molecular Biology and Biotechnology (IMBB), Foundation of Research and Technology-Hellas, Heraklion, Crete, Greece.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Pavlidis
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Emre
authors.initials: E
authors.lastname: Karakoc
authors.affiliation: Department of Computer Science and Engineering, State University of New York at Buffalo, NY, US.
authors.forename: Jerry
authors.initials: J
authors.lastname: Ajay
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, NY, US omergokc@buffalo.edu.
authors.forename: Omer
authors.initials: O
authors.lastname: Gokcumen
mesh_terms: D000483:Alleles; D000818:Animals; D019143:Evolution, Molecular; D014644:Genetic Variation; D016678:Genome; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D017384:Sequence Deletion
keywords: ACOT1; DMBT1; Denisovan; GHR; GSTT1; LCE3C; Neandertal; copy number variation (CNV)