title: Segmental duplications and evolutionary acquisition of UV damage response in the SPATA31 gene family of primates and humans.
abstract: Segmental duplications are an abundant source for novel gene functions and evolutionary adaptations. This mechanism of generating novelty was very active during the evolution of primates particularly in the human lineage. Here, we characterize the evolution and function of the SPATA31 gene family (former designation FAM75A), which was previously shown to be among the gene families with the strongest signal of positive selection in hominoids. The mouse homologue for this gene family is a single copy gene expressed during spermatogenesis.
  
  
  
  We show that in primates, the SPATA31 gene duplicated into SPATA31A and SPATA31C types and broadened the expression into many tissues. Each type became further segmentally duplicated in the line towards humans with the largest number of full-length copies found for SPATA31A in humans. Copy number estimates of SPATA31A based on digital PCR show an average of 7.5 with a range of 5-11 copies per diploid genome among human individuals. The primate SPATA31 genes also acquired new protein domains that suggest an involvement in UV response and DNA repair. We generated antibodies and show that the protein is re-localized from the nucleolus to the whole nucleus upon UV-irradiation suggesting a UV damage response. We used CRISPR/Cas mediated mutagenesis to knockout copies of the gene in human primary fibroblast cells. We find that cell lines with reduced functional copies as well as naturally occurring low copy number HFF cells show enhanced sensitivity towards UV-irradiation.
  
  
  
  The acquisition of new SPATA31 protein functions and its broadening of expression may be related to the evolution of the diurnal life style in primates that required a higher UV tolerance. The increased segmental duplications in hominoids as well as its fast evolution suggest the acquisition of further specific functions particularly in humans.
authors.affiliation: Max-Planck Institute for Evolutionary Biology, August-Thienemann Strasse 2, 24306, Plön, Germany. bekpen@evolbio.mpg.de.
authors.forename: Cemalettin
authors.initials: C
authors.lastname: Bekpen
authors.affiliation: Max-Planck Institute for Evolutionary Biology, August-Thienemann Strasse 2, 24306, Plön, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Künzel
authors.affiliation: Max-Planck Institute for Evolutionary Biology, August-Thienemann Strasse 2, 24306, Plön, Germany.
authors.forename: Chen
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, 14260-1300, NY, USA.|Present address: Population Genomics and Genetic Epidemiology Unit, Dasman Diabetes Institute, P.O.Box 1180, Dasman, 15462, Kuwait.
authors.forename: Muthukrishnan
authors.initials: M
authors.lastname: Eaaswarkhanth
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, 14260-1300, NY, USA.
authors.forename: Yen-Lung
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, 14260-1300, NY, USA.
authors.forename: Omer
authors.initials: O
authors.lastname: Gokcumen
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, CH-7270, Switzerland.
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.affiliation: Max-Planck Institute for Evolutionary Biology, August-Thienemann Strasse 2, 24306, Plön, Germany. tautz@evolbio.mpg.de.
authors.forename: Diethard
authors.initials: D
authors.lastname: Tautz
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D056915:DNA Copy Number Variations; D004249:DNA Damage / Q000528:radiation effects*; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D005810:Multigene Family; D010802:Phylogeny; D011323:Primates / Q000235:genetics*; D000072417:Protein Domains / Q000235:genetics; D056916:Segmental Duplications, Genomic; D014466:Ultraviolet Rays
keywords: Comparative Genomics; Copy number variation; Core duplicons; SPATA31 gene family; Segmental Duplications; UV response