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旧大陆骆驼科动物的主要组织相容性复合体及其II类基因的低多态性。

The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes.

作者信息

Plasil Martin, Mohandesan Elmira, Fitak Robert R, Musilova Petra, Kubickova Svatava, Burger Pamela A, Horin Petr

机构信息

Department of Animal Genetics, Veterinary and Pharmaceutical University, Brno, Czech Republic.

Ceitec VFU, RG Animal Immunogenomics, Brno, Czech Republic.

出版信息

BMC Genomics. 2016 Mar 1;17:167. doi: 10.1186/s12864-016-2500-1.

Abstract

BACKGROUND

The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci.

RESULTS

Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is "Centromere - Class II - Class III - Class I". DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist.

CONCLUSIONS

This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species.

摘要

背景

主要组织相容性复合体(MHC)是一个基因组区域,包含在免疫反应中起关键作用的基因。MHC I类和II类基因编码在细胞表面表达的抗原呈递分子。为了应对病原体的高度变异性,MHC在其组织、数量和多态性程度上进化为一个具有相当大异质性的区域。对不同模式物种中MHC的研究有助于我们理解免疫机制、疾病及其进化。骆驼是具有重要经济价值的家畜和有趣的生物模型。已确认有三种旧大陆骆驼:单峰骆驼(Camelus dromedarius)、双峰骆驼(Camelus bactrianus)和野生骆驼(Camelus ferus)。尽管它们很重要,但关于骆驼的MHC基因组区域及其组织和多样性却知之甚少。本研究的目的是鉴定、定位和表征旧大陆骆驼科动物的MHC区域,特别关注选定的MHC II类基因座的遗传变异。

结果

物理图谱将MHC区域定位到单峰骆驼的20号染色体上。细胞遗传学和全基因组序列的比较分析表明,三个主要子区域的顺序是“着丝粒 - II类 - III类 - I类”。编码相应II类抗原呈递分子抗原结合位点的DRA、DRB、DQA和DQB外显子2序列在这三个物种中显示出高度的序列相似性和广泛的等位基因共享。尽管所分析的骆驼来自不同的地理区域,但在所有物种中均观察到等位基因和单倍型数量出乎意料的低多态性程度。发现DRA基因座具有多态性,所有三个物种共有三个等位基因。从单峰骆驼的古代DNA样本中检索到的DRA和DQA序列表明可能存在其他多态性。

结论

本研究提供了证据,表明骆驼在其基因组定位、组织和序列相似性方面拥有与其他哺乳动物物种相当的MHC。我们描述了在大多数物种中为单态的DRA基因座的古代变异。旧大陆骆驼中MHC II类基因的分子多样性程度似乎远低于其他哺乳动物物种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a23/4774177/f35602c1f608/12864_2016_2500_Fig1_HTML.jpg

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