Characterization, Polymorphism and Selection of Major Histocompatibility Complex (MHC) DAB Genes in Vulnerable Chinese Egret (<i>Egretta eulophotes</i>)

<div><p>The major histocompatibility complex (MHC) is an excellent molecular marker for the studies of evolutionary ecology and conservation genetics because it is a family of highly polymorphic genes that play a key role in vertebrate immune response. In this study, the functional genes of MHC Class II B (DAB) were isolated for the first time in a vulnerable species, the Chinese egret (<i>Egretta</i><i>eulophotes</i>). Using a full length DNA and cDNA produced by PCR and RACE methods, four potential MHC DAB loci were characterized in the genome of this egret and all four were expressed in liver and blood. At least four copies of the MHC gene complex were similar to two copies of the minimal essential MHC complex of chicken, but are less complex than the multiple copies expressed in passerine species. In MHC polymorphism, 19 alleles of exon 2 were isolated from 48 individuals using PCR. No stop codons or frameshift mutations were found in any of the coding regions. The signatures of positive selection detected in potential peptide-binding regions by Bayesian analysis, suggesting that all of these genes were functional. These data will provide the fundamental basis for further studies to elucidate the mechanisms and significance of MHC molecular adaptation in vulnerable Chinese egret and other ardeids.</p> </div

Amino acid alignment of transcribed Chinese egret MHC class II β chain sequences compared with those of other bird species.

<p><i>Dots</i> indicate identity with the Egeu-DAB1*01 sequence, <i>dashes</i> indicate gaps. Conserved residues characteristic of classical class II β chain molecules [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074185#B41" target="_blank">41</a>] are <i>shaded</i>. Amino acids that contact the peptide-binding region in the human DRβ molecule [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074185#B42" target="_blank">42</a>] are indicated with a <i>plus sign</i> (on alignment top). Cysteine bridges in the β1 and β2 domains are indicated by <i>brackets</i>. Residues in the β2 domain that are implicated in CD4 binding in humans are boxed. Species and accession numbers for other bird sequences are as follows: ArciDAB1 Grey Heron, HM991016; ArciDAB2 Grey Heron, HM991017; TyalDAB1 Barn Owl, EU442606; TyalDAB2 Barn Owl, EU442607; ApowDAB01 kiwi, HQ639683, ApowDAB05 kiwi, HQ639685; GagaBLBII chicken, NM_001044679.</p

Allele frequency of MHC class I genes in the Chinese egret.

<p>Allele frequency of MHC class I genes in the Chinese egret.</p

Comparison of amino acid alignment of transcribed MHC class I alpha chain sequences in the Chinese egret with those in other bird species.

<p><i>Dots</i> indicate identity with Egeu-UAA, <i>dashes</i> indicate gaps. Conserved sequence features with predicted functional or structural roles are shown as: peptide main chain binding residues (<i>dark grey shading</i>), intra- and inter-domain contacts (<i>light grey shading</i>), intra-domain disulfide bridges (<i>horizontal lines</i>), CD8 binding sites (<i>“8”s</i>), critical CD8 co-receptor sites (<i>*</i>) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176671#pone.0176671.ref033" target="_blank">33</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176671#pone.0176671.ref034" target="_blank">34</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176671#pone.0176671.ref039" target="_blank">39</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176671#pone.0176671.ref040" target="_blank">40</a>]. Sequence sources are: Grca (Florida sandhill crane, <i>Grus canadensis pratensis</i>, AF033106); Gaga (chicken, <i>G</i>. <i>gallus</i> BF2, AL023516); Anpl (mallard duck, <i>Anus platyrhynchos</i> UAA, AY885227); Lasc-UAA (red-billed gulls, <i>Larus scopulinus</i> UAA, HM015819); Lasc-UBA (red-billed gulls, <i>Larus scopulinus</i> UBA, HM015820); Caca (Red Knot, <i>Calidris canutus</i>, KC205116).</p

Summary of parameter estimates and likelihood values of different models of codon evolution for exon 3 of MHC class I genes in the Chinese egret.

<p>Summary of parameter estimates and likelihood values of different models of codon evolution for exon 3 of MHC class I genes in the Chinese egret.</p

Schematic illustration of MHC II B genes in the Chinese egret.

<p>Egeu-DAB1, Egeu-DAB2, Egeu-DAB3 and Egeu-DAB4 are labeled as A, B, C and D respectively. Exons are represented in boxes. Functional domains are indicated in light grey. The highly divergent regions encompassing intron 1. LP, leader peptide; TM, trans-membrane domain; CY, cytoplasmic domain.</p

Diversity and selection of MHC class I genes in the vulnerable Chinese egret (<i>Egretta eulophotes</i>)

<div><p>The genes of major histocompatibility complex (MHC) are important to vertebrate immune system. In this study, two new MHC class I genes, designated as Egeu-UAA and Egeu-UBA, were discovered in the vulnerable Chinese egret (<i>Egretta eulophotes</i>). Using a full length DNA and cDNA produced by PCR and RACE methods, these two MHC class I loci were characterized in the genome of the Chinese egret and were also found to be expressed in liver and blood. Both new genes showed the expected eight exons and were similar to two copies of the minimal essential MHC complex of chicken. In genetic diversity, 14 alleles (8 for UAA and 6 for UBA) in the MHC class I gene exon 3 were found in 60 individuals using locus-specific primers and showed little polymorphism. Only three potential amino acid residues were detected under positive selection in potential peptide-binding regions (PBRs) by Bayesian analysis. These new results provide the fundamental basis for further studies to elucidate the molecular mechanisms and significance of MHC molecular adaptation in vulnerable Chinese egret and other ardeids, finding that have not been previously reported.</p></div

Summary of sequence variation of MHC class I in the Chinese egret.

<p>Summary of sequence variation of MHC class I in the Chinese egret.</p

Additional file 2 of Genomic insight into the nocturnal adaptation of the black-crowned night heron (Nycticorax nycticorax)

Additional file 2: Supplement Table S1. xls

Genetic risk and gastric cancer: polygenic risk scores in population-based case-control study

This study aimed to screen and identify common variants and long noncoding RNA (lncRNA) single nucleotide polymorphisms (SNPs) associated with gastric cancer risk, and construct prediction models based on polygenic risk score (PRS). The risk factors associated with gastric cancer were screened following meta-analysis and bioinformatics, verified by population-based case-control study. We constructed PRS and weighted genetic risk scores (wGRS) derived from the validation data set. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to evaluate model. The PRS was divided into 10 quantiles, with the 40–60% quantile as a reference. A risk gradient was revealed across quantile of the PRS, the risk of gastric cancer in the highest 10 quantile of PRS was 3.24-fold higher than that in control population (OR = 3.24, 95%CI: 2.07, 5.06). For NRI and IDI, PRS combinations were significantly improved compared to wGRS model combinations (P  The model based on PRS combined with lncRNA SNPs, H. pylori infection, smoking, and drinking had the optimal predictive ability for gastric cancer risk, which was helpful to distinguish high-risk groups.</p