Xue, James R.Mackay-Smith, AvaMouri, KousukeFernandez Garcia, MeilinDong, Michael X.Akers, Jared F.Noble, MarkLi, XueZoonomia ConsortiumLindblad-Toh, KerstinKarlsson, Elinor K.Noonan, James P.Capellini, Terence D.Brennand, Kristen J.Tewhey, RyanSabeti, Pardis C.Reilly, Steven K.2024-03-252024-03-252023Xue JR, Mackay-Smith A, Mouri K, Garcia MF, Dong MX, Akers JF, et al. The functional and evolutionary impacts of human-specific deletions in conserved elements. Science. 2023 Apr 28;380(6643):eabn2253. DOI: 10.1126/science.abn22530036-8075http://hdl.handle.net/10230/59550Conserved genomic sequences disrupted in humans may underlie uniquely human phenotypic traits. We identified and characterized 10,032 human-specific conserved deletions (hCONDELs). These short (average 2.56 base pairs) deletions are enriched for human brain functions across genetic, epigenomic, and transcriptomic datasets. Using massively parallel reporter assays in six cell types, we discovered 800 hCONDELs conferring significant differences in regulatory activity, half of which enhance rather than disrupt regulatory function. We highlight several hCONDELs with putative human-specific effects on brain development, including HDAC5, CPEB4, and PPP2CA. Reverting an hCONDEL to the ancestral sequence alters the expression of LOXL2 and developmental genes involved in myelination and synaptic function. Our data provide a rich resource to investigate the evolutionary mechanisms driving new traits in humans and other species.application/pdfengThis is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 2023 Apr 28;380(6643):eabn2253, DOI: 10.1126/science.abn2253.Genòmica funcionalinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1126/science.abn2253info:eu-repo/semantics/openAccess