Busch Joseph D, Waser Peter M, DeWoody J Andrew
Department of Forestry and Natural Resources, Purdue University, West Lafayette, IN 47907, USA.
Immunogenetics. 2008 Nov;60(11):677-88. doi: 10.1007/s00251-008-0323-1. Epub 2008 Oct 3.
Genes of the major histocompatibility complex (MHC) are exceptionally polymorphic due to the combined effects of natural and sexual selection. Most research in wild populations has focused on the second exon of a single class II locus (DRB), but complete gene sequences can provide an illuminating backdrop for studies of intragenic selection, recombination, and organization. To this end, we characterized class II loci in the banner-tailed kangaroo rat (Dipodomys spectabilis). Seven DRB-like sequences (provisionally named MhcDisp-DRB01 through 07) were isolated from spleen cDNA and most likely comprise > or =5 loci; this multiformity is quite unlike the situation in muroid rodents such as Mus, Rattus, and Peromyscus. In silico translation revealed the presence of important structural residues for glycosylation sites, salt bonds, and CD4+ T-cell recognition. Amino-acid distances varied widely among the seven sequences (2-34%). Nuclear DNA sequences from the Disp-DRB07 locus (approximately 10 kb) revealed a conventional exon/intron structure as well as a number of microsatellites and short interspersed nuclear elements (B4, Alu, and IDL-Geo subfamilies). Rates of nucleotide substitution at Disp-DRB07 are similar in both exons and introns (pi = 0.015 and 0.012, respectively), which suggests relaxed selection and may indicate that this locus is an expressed pseudogene. Finally, we performed BLASTn searches against Dipodomys ordii genomic sequences (unassembled reads) and find 90-97% nucleotide similarity between the two kangaroo rat species. Collectively, these data suggest that class II diversity in heteromyid rodents is based on polylocism and departs from the muroid architecture.
由于自然选择和性选择的共同作用，主要组织相容性复合体（MHC）的基因具有极高的多态性。野生种群中的大多数研究都集中在单个II类基因座（DRB）的第二个外显子上，但完整的基因序列可为基因内选择、重组和组织研究提供有启发性的背景。为此，我们对旗尾更格卢鼠（Dipodomys spectabilis）的II类基因座进行了表征。从脾脏cDNA中分离出七个DRB样序列（暂命名为MhcDisp-DRB01至07），很可能包含≥5个基因座；这种多样性与小家鼠、大鼠和鹿鼠等鼠形啮齿动物的情况截然不同。电子翻译显示存在糖基化位点、盐键和CD4+ T细胞识别的重要结构残基。七个序列之间的氨基酸距离差异很大（2%-34%）。Disp-DRB07基因座的核DNA序列（约10 kb）显示出传统的外显子/内含子结构以及一些微卫星和短散在核元件（B4、Alu和IDL-Geo亚家族）。Disp-DRB07外显子和内含子的核苷酸替代率相似（分别为π = 0.015和0.012），这表明选择压力有所放松，可能表明该基因座是一个已表达的假基因。最后，我们对Ordii更格卢鼠的基因组序列（未组装读数）进行了BLASTn搜索，发现这两种更格卢鼠物种之间的核苷酸相似性为90%-97%。总体而言，这些数据表明异鼠科啮齿动物的II类多样性基于多基因座，与鼠形啮齿动物的结构不同。
