Evolution of copy number variation in the rhesus macaque β-defensin region

2014-07-04T08:43:10Z (GMT) by Barbara Ottolini
Beta defensins are multifunctional secreted short peptides rapidly evolving in mammals. They present antibacterial and antiviral action in many species and possess immune cell signal activity, constituting a link between innate and adaptive immunity. In humans the β-defensin region is known to be copy number variable (CNV) and contains seven genes repeated as a block, with a diploid copy number between 1 and 12 and an approximate repeat length of 240kb but the extent and nature of CNV in other mammals remains poorly known. The rhesus macaque (Macaca mulatta) is the most widespread non-human primate, hence constituting a good model to study adaptation and its divergence time from the human lineage (~25MYA) presents enough sequence diversity to investigate mechanisms of copy number variation and evolution. Its genome has been sequenced, although there is poor assembly quality in repeated segments such as the β-defensin region. This thesis studied the genomic architecture of the rhesus macaque β-defensin region using a variety of methods (aCGH, PCR-based methods, BAC library screening and cytogenetic approaches) with the aim of overcoming the limitations of the assembly and of determining the copy number distribution for this region. Evidences are here provided that only the region containing DEFB2L gene (orthologue to human DEFB4) is CNV, with a diploid copy number between 2 and 11, with a repeat size of 20kb, while the rest of the cluster shows no variation. This could represent a case where the same area prone to copy number variation evolved to present a different copy number unit structure in two different lineages, still converging in the same copy number distribution for the possible effect of similar functional constraints. Also, evidences of non-synonymous variations are shown for the DEFB2L gene, suggestive of the different evolutionary pattern followed by the rhesus macaque β-defensin region.




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