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Genetic diversity comparison of the DQA gene in European rabbit (Oryctolagus cuniculus) populations

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Abstract

The European rabbit (Oryctolagus cuniculus) natural populations within the species native region, the Iberian Peninsula, are considered a reservoir of genetic diversity. Indeed, the Iberia was a Pleistocene refuge to the species and currently two subspecies are found in the peninsula (Oryctolagus cuniculus cuniculus and Oryctolagus cuniculus algirus). The genes of the major histocompatibility complex (MHC) have been substantially studied in wild populations due to their exceptional variability, believed to be pathogen driven. They play an important function as part of the adaptive immune system affecting the individual fitness and population viability. In this study, the MHC variability was assessed by analysing the exon 2 of the DQA gene in several European rabbit populations from Portugal, Spain and France and in domestic breeds. Twenty-eight DQA alleles were detected, among which 18 are described for the first time. The Iberian rabbit populations are well differentiated from the French population and domestic breeds. The Iberian populations retained the higher allelic diversity with the domestic breeds harbouring the lowest; in contrast, the DQA nucleotide diversity was higher in the French population. Signatures of positive selection were detected in four codons which are putative peptide-binding sites and have been previously detected in other mammals. The evolutionary relationships showed instances of trans-species polymorphism. Overall, our results suggest that the DQA in European rabbits is evolving under selection and genetic drift

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Acknowledgments

This work was funded by FEDER funds through the Operational Program for Competitiveness Factors - COMPETE and by National Funds through FCT - Foundation for Science and Technology under the project PTDC/BIA-ANM/3963/2012 and FCOMP-01-0124-FEDER-028286. FCT also supported the FCT Investigator grant of Joana Abrantes (ref.: IF/01396/2013). AJMP is supported by a postdoctoral fellowship funded by CIBIO-InBIO (UID/BIA/50027/2013). VM is supported by a postdoctoral fellowship funded by CIBIO-InBIO a posESCTNPIIC&DT/1/2011) “Genomics Applied to Genetic Resources” co-financed by North Portugal Regional Operational Programme 2007/2013 (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF), also supported this work.

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Correspondence to Pedro J. Esteves.

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The GeneBank accession numbers for the new sequences of the DQA exon 2 determined in this study are: KR534620, KR534621, KR534622, KR534623, KR534624, KR534625, KR534626, KR534627, KR534628, KR534629, KR534630, KR534631, KR534632, KR534633, KR534634, KR534635, KR534636 and KR534637.

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ESM 1

Amino acid diversity of the 75 DQA sequences leporid dataset. Amino acids are numbered according to the aligned protein translation given for human and rabbit DQA genes in Ensembl (www.ensembl.org). ‡ denotes the new rabbit DQA haplotypes detected in this study. The nomenclature Orcu DQA*01 = Allele A, Orcu DQA*05 = Allele B/E, Orcu DQA*10 = Allele C, Orcu DQA*12 = Allele D, Orcu DQA*09 = Allele G and Orcu DQA*19 = Allele F was used following (Fain et al. 2001 and Surridge et al. 2008). Species abbreviations: Sybr (Tapeti rabbit, Sylvilagus brasiliensis), Syfl (Eastern cottontail, Sylvilagus floridanus), Sytr (New England cottontail, Sylvilagus transitionalis), Syau (Audubon´s cottontail, Sylvilagus audubonii), Syaq (Swamp rabbit, Sylvilagus aquaticus), Prru (Red rock rabbit, Pronolagus rupestris), Leeu (European brown hare, Lepus Europaeus), Leti (Mountain hare, Lepus timidus), Legr (Iberian hare, Lepus granatensis), Lesa (Scrub hare, Lepus saxatilis), Lecp (Cape hare, Lepus capensis), Leto (White-tailed jackrabbit, Lepus townsendii) and Leya (Yarkland hare, Lepus yarkandensis) (DOCX 20 kb)

ESM 2

Median-joining network of the DQA haplotypes of the European rabbits used in this study. Each circle corresponds to an assigned haplotype (H1-H28; see Fig. 1): in yellow are the haplotypes found in domestic breeds, in black the wild French, in blue the wild Spanish and in red the wild Portuguese rabbits populations. The inferred missing intermediate haplotypes are represented by grey circles. Circle size represents allele frequency. Lines connect each haplotype to its most similar relative. G1, G2 and G3 refer to the clusters corresponding to the three assigned clades in Fig. 2 (DOCX 250 kb)

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Magalhães, V., Abrantes, J., Munõz-Pajares, A.J. et al. Genetic diversity comparison of the DQA gene in European rabbit (Oryctolagus cuniculus) populations. Immunogenetics 67, 579–590 (2015). https://doi.org/10.1007/s00251-015-0866-x

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