Journal Article

An evolutionary driver of interspersed segmental duplications in primates

Sorensen, Melanie, Sulovari, Arvis, Welch, AnneMarie E., Girirajan, Santhosh, Anaclerio, Fabio, Munson, Katherine M., Lamb, Bruce T., Sunkin, Susan M., Johnson, Matthew E., Catacchio, Claudia Rita, Eichler, Evan E., Huddleston, John, Underwood, Jason G., Malig, Maika, Cantsilieris, Stuart, Dougherty, Max L., Conlon, Ronald A., Hsieh, PingHsun, Mao, Yafei, Baker, Carl, Ventura, Mario, Jiang, Weihong

2020

Overview

Background The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the evolution of LCR16a, a putative driver of this phenomenon that encodes one of the most rapidly evolving human–ape gene families, nuclear pore interacting protein ( NPIP ). Results Comparative analysis shows that LCR16a has independently expanded in five primate lineages over the last 35 million years of primate evolution. The expansions are associated with independent lineage-specific segmental duplications flanking LCR16a leading to the emergence of large interspersed duplication blocks at non-orthologous chromosomal locations in each primate lineage. The intron-exon structure of the NPIP gene family has changed dramatically throughout primate evolution with different branches showing characteristic gene models yet maintaining an open reading frame. In the African ape lineage, we detect signatures of positive selection that occurred after a transition to more ubiquitous expression among great ape tissues when compared to Old World and New World monkeys. Mouse transgenic experiments from baboon and human genomic loci confirm these expression differences and suggest that the broader ape expression pattern arose due to mutational changes that emerged in cis. Conclusions LCR16a promotes serial interspersed duplications and creates hotspots of genomic instability that appear to be an ancient property of primate genomes. Dramatic changes to NPIP gene structure and altered tissue expression preceded major bouts of positive selection in the African ape lineage, suggestive of a gene undergoing strong adaptive evolution.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Animal Genetics and Genomics / Animal models / APE gene / Bioinformatics / Biomedical and Life Sciences / brain / Chromosomes / Cloning / Comparative analysis / Evolution & development / evolutionary adaptation / Evolutionary Biology / Evolutionary genetics / Gene families / Gene fusion / Gene loci / genes / genetic instability / genetically modified organisms / Genomes / Genomic instability / genomics / Human Genetics / humans / Hybridization / LCR16a / Life Sciences / mice / Microbial Genetics and Genomics / Monkeys & apes / Neurodevelopmental disorders / nuclear pore / Nuclear pore interacting protein / Papio / Plant Genetics and Genomics / Pongidae / Positive selection / Segmental duplication