Stronger effects were seen in the Cl2 cells (Fig.?6a). 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 Namitecan cell lines with reduced functional copies as well as naturally occurring low copy number HFF cells show enhanced sensitivity towards UV-irradiation. Conclusion The acquisition of new 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. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3595-8) contains supplementary material, which is available to authorized users. gene family (previously known as in mice (previously known as gene family expanded within the great apes by segmental duplication from one copy in mice to two copies in macaque and to multiple functional and non-functional copies along chromosome 9 in hominoid primates and humans. The gene in primates acquired new upstream sequences that have led to broader expression and new protein domains suggesting an involvement in sensing and/or repairing UV damage. We provide experimental evidence in cell cultures that support this hypothesis. Results and discussion Gene duplication patterns We conducted a detailed analysis of gene structure evolution and duplication patterns of based on genome sequence comparisons. The mouse harbors a single copy of the gene on chromosome 13. In the macaque, there are two copies of and gene family expansion in humans. The gene structure and chromosome localization of genes based on the human reference (hg38), rhesus macaque (rheMac3) and mouse (mm10) genomes are shown. The mouse harbors a single copy that has duplicated and diverged into an A and a C type in macaque. Mouse monoclonal to AFP Further segmental duplications are found in humans on chromosome 9 Type A has seven segmental duplications in humans (numbers based on human genome build hg38), of which one is a clear pseudogene due to multiple stop codons (P1). Another encodes a truncated protein (P2) due to a frameshift mutation resulting in a premature stop codon in exon 4 (Fig.?1). Note that the annotation around and is uncertain because short non-sequenced regions interrupt the region. Type C has two copies in the human genomeeach is usually preceded by a duplication of the first exon including the promoter sequence (Fig.?1). However, these additional promoters do not appear to initiate transcripts. The gene lengths and the protein coding regions of genes differ between A and C types. The predicted molecular weights are 157 kD for the A type (A1) and 130 kD for the C type (C1). To trace the Namitecan growth of the family, we assessed copy numbers in fully sequenced genomes of sequenced individuals from macaque, orangutan, chimps and twelve humans including Us_Ishim, Denisovan and Neandertal. The results show that there was on average a progressive increase of segmental duplications of the gene locus towards humans (Additional File 2). A detailed comparison of the promoter regions including (MD and MER31A) elements revealed that there are two different Namitecan general promoter structures shared by all and genes respectively (Fig.?2 and Additional File 3). In particular, the promoter region of was subjected to multiple rounds of rearrangement resulting in a composite promoter structure consisting of three promoters are composed of LINE/L1-P3 and PA10 retroviral elements (Additional File 3). The main expansion of the PA10 element occurred Namitecan about 65 Mya and the expansion of the P3 element occurred about 35 Mya (reviewed in  and ). Accordingly, no P3 element is detected in the promoter regions of New World Monkeys. An insertion of a CCCCCT simple repeat is observed in gorillas, chimpanzees and humans at the time where the main growth of the family is usually observed. Thus, we propose that the promoter region of was restructured in a stepwise manner by integration of LINE and a CCCCCT simple repeat within the primate phylogeny (Fig.?2). Open in a separate windows Fig. 2 Evolutionary emergence of the human gene promoter structures. Phylogenetic reconstruction of full length SPATA31 proteins (exon4 – longest coding exon) in different primates, cat, doggie, rat and mouse species using the NJ.