Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes

• Published in: Science (American Association for the Advancement of Science) Vol. 366; no. 6463; p. 324
• Main Authors: Hsieh, PingHsun, Vollger, Mitchell R., Dang, Vy, Porubsky, David, Baker, Carl, Cantsilieris, Stuart, Hoekzema, Kendra, Lewis, Alexandra P., Munson, Katherine M., Sorensen, Melanie, Kronenberg, Zev N., Murali, Shwetha, Nelson, Bradley J., Chiatante, Giorgia, Maggiolini, Flavia Angela Maria, Blanché, Hélène, Underwood, Jason G., Antonacci, Francesca, Deleuze, Jean-François, Eichler, Evan E.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 18.10.2019; The American Association for the Advancement of Science
• Subjects: Adaptation; Amino acids; Animals; Autism; Base pairs; Biochemistry, Molecular Biology; Biological evolution; Cell cycle; Chromosome 16; Chromosome 8; Chromosome Duplication; Chromosomes; Chromosomes, Human, Pair 16 - genetics; Chromosomes, Human, Pair 8 - genetics; Clonal deletion; Copy number; Demographics; DNA Copy Number Variations; Duplication; Evidence; Evolution, Molecular; Evolutionary genetics; Gene duplication; Gene mapping; Genes; Genetic diversity; Genetic Introgression; Genetic variance; Genetics; Genome, Human; Genomes; Genomics; Haplotypes; High frequencies; Hominidae - genetics; Hominids; Homo sapiens denisova; Human populations; Humans; Immune response; Individualized Instruction; Life Sciences; Local population; Melanesia; Models, Genetic; Mountains; Mutation; Neanderthals - genetics; Nucleotides; Polymorphism, Genetic; Population; Population genetics; Populations; Positive selection; Reproduction (copying); RESEARCH ARTICLE SUMMARY; Selection, Genetic; Signatures; Whole Genome Sequencing; Melanesia; Africa
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aax2083

As they migrated out of Africa and into Europe and Asia, anatomically modern humans interbred with archaic hominins, such as Neanderthals and Denisovans. The result of this genetic introgression on the recipient populations has been of considerable interest, especially in cases of selection for specific archaic genetic variants. Hsieh et al. characterized adaptive structural variants and copy number variants that are likely targets of positive selection in Melanesians. Focusing on population-specific regions of the genome that carry duplicated genes and show an excess of amino acid replacements provides evidence for one of the mechanisms by which genetic novelty can arise and result in differentiation between human genomes. Science , this issue p. eaax2083 Melanesians carry adaptive DNA variants derived from archaic hominins. Copy number variants (CNVs) are subject to stronger selective pressure than single-nucleotide variants, but their roles in archaic introgression and adaptation have not been systematically investigated. We show that stratified CNVs are significantly associated with signatures of positive selection in Melanesians and provide evidence for adaptive introgression of large CNVs at chromosomes 16p11.2 and 8p21.3 from Denisovans and Neanderthals, respectively. Using long-read sequence data, we reconstruct the structure and complex evolutionary history of these polymorphisms and show that both encode positively selected genes absent from most human populations. Our results collectively suggest that large CNVs originating in archaic hominins and introgressed into modern humans have played an important role in local population adaptation and represent an insufficiently studied source of large-scale genetic variation.