Study of cynomolgus monkey (Macaca fascicularis) DRA polymorphism in four populations
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To describe the polymorphism of the DRA gene in Macaca fascicularis, we have studied 141 animals either at cDNA level (78 animals from Mauritius, the Philippines, and Vietnam) or genomic level (63 animals from the Philippines, Indonesia, and Vietnam). In total, we characterized 22 cDNA DRA alleles, 13 of which had not been described until now. In the Mauritius population, we confirmed the presence of three DRA alleles. In the Philippine and Vietnam populations, we observed 11 and 14 DRA alleles, respectively. Only two alleles were present in all three populations. All DRA alleles but one differ from the consensus sequence by one to three mutations, most being synonymous; so, only seven DR alpha proteins were deduced from the 22 cDNA alleles. One DRA cDNA allele, Mafa-DRA*02010101, differs from all other alleles by 11 to 14 mutations of which only four are non-synonymous. The two amino acid changes inside the peptide groove of Mafa-DRA*02010101 are highly conservative. The very low proportion of non-synonymous/synonymous mutations is compatible with a purifying selection which is comparable to all previous observations concerning the evolution of the DRA gene in mammals. Homologues of the allele Mafa-DRA*02010101 are also found in two other Asian macaques (Macaca mulatta and Macaca nemestrina). The forces able to maintain this highly divergent allele in three different macaque species remain hypothetical.
KeywordsMHC DRA Macaque Polymorphism
This work was performed with funds from the French Ministry of Research (EA3034 contract), from a research grant from Novartis, and with the help of ANRS (contract number 07375). Other funds were from the Laboratory of Dr. Takashi Shiina. We thank Pr. Brigitte Le Mauf (Nantes, France), Dominic Borie (Stanford, USA), Eric André (Bioprim, Baziège, France), Marc Bigaud (Novartis, Bâle), Dr. Jacques Ducos de Lahitte (Ecole Nationale Vétérinaire de Toulouse), for their help in obtaining macaque blood samples. Our thanks are also due to Peter Winterton for his contribution in drawing up the final version of this manuscript.
We are pleased to thank all the technicians of the Toulouse Laboratory of Immunogenetics: Béatrice Atlan, Audrey Dauba, Stéphanie Despiau-Schiavinato, and Sylvie Hébrard for their excellent technical assistance.
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