Abstract
The major histocompatibility complex (MHC) is a fundamental part of the immune system in nearly all vertebrates. DQA2 is a member of the MHC complex and an important candidate gene involved in susceptibility/resistance to various diseases. Therefore, the present study aimed at investigating computationally molecular genetic variation of DQA2 gene of cattle, sheep and goats especially on its evolution and differentiation within and among species as well as the attendant effects of the polymorphism on the function of DQA2 gene. A total of thirty three DQA2 nucleotide sequences comprising cattle (10), sheep (12) and goats (11) were retrieved from the GenBank. Forty seven amino acid substitutions of the wild type alleles located in the putative peptide coding region of caprine DQA2 alleles were obtained from the alignment of deduced amino acid sequences of goats. Out of these, eleven amino acid substitutions (H14L, H14R, L34M, E35L, G56S, G56R, 161V, A62E, D69Q, T72N and T72G) were returned neutral; an indication that they did not impair protein function. The Expected Accuracy (EA) ranged from 53% - 87%. For sheep, sixteen amino acid substitutions (A11P, A11T, A11G, A11M, L14S, L14T, V27L, V27S, G35S, S46T, D55E, L57T, L57A, L57G, K65Q and V68I) appeared beneficial while the rest forty seven appeared harmful (EA ranged from 53% - 93%). Twenty four amino acid substitutions did not impair the function of protein while seventy seven substitutions appeared to have a negative effect on the function of protein of cattle (EA ranged from 53% - 94%). The phylogeny based on nucleotide and amino acid sequences of DQA2 gene revealed the close relatedness of the caprine, ovine and bovine species. The present knowledge would be relevant for performing further genotype-phenotype research as well as pharmacogenetics studies in order to show association between caprine, ovine and bovine DQA2 allelic variation and the clinical progression of infectious diseases especially in a developing country such as Nigeria.
Highlights
Genetic variation in parasite and host and relative distribution across space and time is of great interest and serves as a basis for adaptive change
Forty seven amino acid substitutions of the wild type alleles located in the putative peptide coding region of caprine DQA2 alleles were obtained from the alignment of deduced amino acid sequences of goats
major histocompatibility complex (MHC) genes are the most polymorphic genes described in vertebrates, with polymorphisms occurring predominantly at residues involved in peptide binding [21]
Summary
Genetic variation in parasite and host and relative distribution across space and time is of great interest and serves as a basis for adaptive change. Spatial population structure can strongly influence the process of coadaptation between parasite and host and the evolution of virulence [1]. MHC molecules play an important role in the immune system and autoimmunity. They are cellular glycoproteins involved in antigen presentation to CD4+ T cells. The genes encoding these molecules are polymorphic [2] [3]. DQ genes of MHC class II region encode for α (DQA) chain of the molecule [4]. According to McKenzie et al [7], DQA2 of sheep is found on chromosome 20
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