Genetic diversity of MHC class I loci in six non-model frogs is shaped by positive selection and gene duplication

Comparative studies of major histocompatibility complex (MHC) genes across vertebrate species can reveal the evolutionary processes that shape the structure and function of immune regulatory proteins. In this study, we characterized MHC class I sequences from six frog species representing three anuran families (Hylidae, Centrolenidae and Ranidae). Using cDNA from our focal species, we amplified a total of 79 unique sequences spanning exons 2-4 that encode the extracellular domains of the functional alpha chain protein. We compared intra- and interspecific nucleotide and amino-acid divergence, tested for recombination, and identified codon sites under selection by estimating the rate of non-synonymous to synonymous substitutions with multiple codon-based maximum likelihood methods. We determined that positive (diversifying) selection was acting on specific amino-acid sites located within the domains that bind pathogen-derived peptides. We also found significant signals of recombination across the physical distance of the genes. Finally, we determined that all the six species expressed two or three putative classical class I loci, in contrast to the single locus condition of Xenopus laevis. Our results suggest that MHC evolution in anurans is a dynamic process and that variation in numbers of loci and genetic diversity can exist among taxa. Thus, the accumulation of genetic data for more species will be useful in further characterizing the relative importance of processes such as selection, recombination and gene duplication in shaping MHC loci among amphibian lineages.     

Protein elemental sparing and codon usage bias are correlated among bacteria

Highly expressed proteins can exhibit relatively small material costs, in terms of the quantities of carbon (C), nitrogen (N) or sulphur (S) atoms they contain. This 'elemental sparing' probably reflects selection to reduce the quantities of potentially growth-limiting elements in abundant proteins, but the evolutionary mechanisms for adaptive elemental sparing are still poorly understood. Here, we predict that the extent of 'elemental sparing' in highly expressed proteins will vary among organisms, according to the effectiveness of selection in determining the fate of mutations. We test this hypothesis in bacteria by asking whether 'elemental sparing' is correlated with codon usage bias. Bacteria exhibit extraordinary variation in their life histories and demography and consequently in the effectiveness of selection in determining whether preferred codons are used in highly expressed genes. We find that C sparing and S sparing, but not N sparing, are significantly correlated with adaptive codon usage bias among 148 genera of bacteria, suggesting that selection for elemental sparing and codon bias are promoted by similar bacterial traits. Our study helps identify principles that determine how nutrient scarcity can shape the elemental composition of proteins.     

家禽主要组织相容性复合体的研究进展

随着家禽基因组计划的开展,对家禽的主要组织相容性复合体（MHC）的研究取得了较大的进展。关于家禽MHC的各部分基因研究正在逐步深入,并且完成了MHC部分测序和染色体定位工作。 本文介绍近些年来对家禽MHC的基因结构和作用、与抗体的作用以及相关的基因组研究所取得的进展。人、小鼠及其他动物的相关研究结果将对家禽MHC研究的发展产生重要的影响。Abstract:As the development of poultry genome project,it has been acquired many advances in the study of poultry MHC.At present,we have achieved some MHC sequences 、 locations of MHC on chromosome and some MHC gene functions.This article give a detailed introduction about gene structure of poultry MHC and its role in immune reaction、relation with antibody and advances in poultry genome about MHC.With the development of related research,how to use the result of the study more efficiently become more and more important to the poultry MHC study.     

Molecular modeling of an antigenic complex between a viral peptide and a class I major histocompatibility glycoprotein.

Computer simulation of the conformations of short antigenic peptides (5-10 residues) either free or bound to their receptor, the major histocompatibility complex (MHC)-encoded glycoprotein H-2 Ld, was employed to explain experimentally determined differences in the antigenic activities within a set of related peptides. Starting for each sequence from the most probable conformations disclosed by a pattern-recognition technique, several energy-minimized structures were subjected to molecular dynamics simulations (MD) either in vacuo or solvated by water molecules. Notably, antigenic potencies were found to correlate to the peptides propensity to form and maintain an overall alpha-helical conformation through regular i,i + 4 hydrogen bonds. Accordingly, less active or inactive peptides showed a strong tendency to form i,i + 3 hydrogen bonds at their N-terminal end. Experimental data documented that the C-terminal residue is critical for interaction of the peptide with H-2 Ld. This finding could be satisfactorily explained by a 3-D Q.S.A.R. analysis postulating interactions between ligand and receptor by hydrophobic forces. A 3-D model is proposed for the complex between a high-affinity nonapeptide and the H-2 Ld receptor. First, the H-2 Ld molecule was built from X-ray coordinates of two homologous proteins: HLA-A2 and HLA-Aw68, energy-minimized and studied by MD simulations. With HLA-A2 as template, the only realistic simulation was achieved for a solvated model with minor deviations of the MD mean structure from the X-ray conformation. Water simulation of the H-2 Ld protein in complex with the antigenic nonapeptide was then achieved with the template-derived optimal parameters. The bound peptide retains mainly its alpha-helical conformation and binds to hydrophobic residues of H-2 Ld that correspond to highly polymorphic positions of MHC proteins. The orientation of the nonapeptide in the binding cleft is in accordance with the experimentally determined distribution of its MHC receptor-binding residues (agretope residues). Thus, computer simulation was successfully employed to explain functional data and predicts alpha-helical conformation for the bound peptide.     

Can genomic data alone tell us whether speciation happened with gene flow?

The allopatric model, which requires a period of geographical isolation for speciation to complete, has been the standard model in the modern era. Recently, “speciation with gene flow” has been widely discussed in relation to the model of “strict allopatry” and the level of DNA divergence across genomic regions. We wish to caution that genomic data by themselves may only permit the rejection of the simplest form of allopatry. Even a slightly more complex and realistic model that starts with subdivided populations would be impossible to reject by the genomic data alone. To resolve this central issue of speciation, other forms of observations such as the sequencing of reproductive isolation genes or the identification of geographical barrier(s) will be necessary.     

Ancestral polymorphism in exon 2 of bluethroat (Luscinia svecica) MHC class II B genes

The genes of the major histocompatibility complex (MHC) are important model genes for understanding selective forces in evolution. Here, we document, using a cloning and sequencing approach, high polymorphism at the exon 2 of the MHC class II B (MHCIIB) genes in the bluethroat (Luscinia svecica); a minimum of 61 unique alleles were detected in 20 individuals, and at least 11 functional loci. In addition, several pseudogenes were revealed. The specimens originated from three different bluethroat subspecies (azuricollis, cyanecula and svecica), and we also analysed four specimens of the closely related thrush nightingale (L. luscinia) for comparison. Phylogenetic analyses of the functional alleles revealed 258 equally parsimonious trees with poor statistical support for the majority of nodes. The distribution of the sequences in the trees point to an ancestral origin of the polymorphism in MHC class II B genes, a portion of which predated the phylogenetic split between the bluethroat and the thrush nightingale. Strong signatures of balancing selection were uncovered for the codons coding for the peptide‐binding residues of the functional MHCIIB exon 2 alleles. Our results highlight the importance of duplication and recombination events for shaping passerine MHC and give insights in the evolutionary dynamics of MHC variation among closely related taxa.