Genomic analysis reveals extensive gene duplication within the bovine TRB locus.

Genomic analysis reveals extensive gene duplication within the bovine TRB locus.
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DOI:
10.1186/1471-2164-10-192
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发表时间:
2009-04-24
期刊:
影响因子:
4.4
通讯作者:
Morrison WI
Morrison WI
中科院分区:
生物学2区
文献类型:
--
作者:
Connelley T;Aerts J;Law A;Morrison WI

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通过V(D)J体细胞重组产生多种TR和IG库。基因组研究在编目存在于各种TR/IG位点的V、D、J和C基因以及描述重复事件如何扩大这些基因的数量方面是关键的。这些研究也为这些基因座的进化和调节TR/IG表达的复杂机制提供了见解。在这项研究中,我们分析了第三个牛基因组组装的序列,以表征牛TRB基因的种系库,并比较牛TRB基因座与人类和小鼠的组织,进化和调控结构。第三次牛基因组组装中的TRB基因座分布在5个支架上,延伸至~730 Kb。现有序列包含134个TRBV基因,分配到24个亚组,和3个DJC基因簇,每个簇包含单个TRBD基因、5-7个TRBJ基因和单个TRBC基因。79个TRBV基因被预测是功能性的。与人类和小鼠TRB基因座的比较表明,基因顺序,以及调节TRB表达的非编码元件的序列,在牛中是高度保守的。点图分析表明,TRBV基因组库的扩展是通过一系列复杂而广泛的复制发生的,主要涉及含有多个基因的DNA块。这些重复事件导致了几个TRBV亚群的大规模扩增,最值得注意的是TRBV 6、9和21,它们分别含有40、35和16个成员。同样,重复导致了第三个DJC集群的产生。cDNA数据的分析证实了TRBV基因的多样性,此外,确定了大量的TRBV基因,主要来自较大的亚组,这仍然是缺席的基因组组装。牛TRB基因座内观察到的基因重复创建了系统发育上多样化的功能性TRBV基因库,其远大于人类和小鼠中描述的基因库。在这项研究中完成的分析表明,尽管牛TRB基因座的基因内容和组织与人类和小鼠的基因内容和组织大致相似,但多次重复事件导致了TRB基因数量的显着扩增。在其他反刍动物TR基因座类似的扩张表明,强大的进化压力,在这个谱系中选择了扩大套TR基因,可以有助于不同的TR剧目的发展。
Diverse TR and IG repertoires are generated by V(D)J somatic recombination. Genomic studies have been pivotal in cataloguing the V, D, J and C genes present in the various TR/IG loci and describing how duplication events have expanded the number of these genes. Such studies have also provided insights into the evolution of these loci and the complex mechanisms that regulate TR/IG expression. In this study we analyze the sequence of the third bovine genome assembly to characterize the germline repertoire of bovine TRB genes and compare the organization, evolution and regulatory structure of the bovine TRB locus with that of humans and mice. The TRB locus in the third bovine genome assembly is distributed over 5 scaffolds, extending to ~730 Kb. The available sequence contains 134 TRBV genes, assigned to 24 subgroups, and 3 clusters of DJC genes, each comprising a single TRBD gene, 5–7 TRBJ genes and a single TRBC gene. Seventy-nine of the TRBV genes are predicted to be functional. Comparison with the human and murine TRB loci shows that the gene order, as well as the sequences of non-coding elements that regulate TRB expression, are highly conserved in the bovine. Dot-plot analyses demonstrate that expansion of the genomic TRBV repertoire has occurred via a complex and extensive series of duplications, predominantly involving DNA blocks containing multiple genes. These duplication events have resulted in massive expansion of several TRBV subgroups, most notably TRBV6, 9 and 21 which contain 40, 35 and 16 members respectively. Similarly, duplication has lead to the generation of a third DJC cluster. Analyses of cDNA data confirms the diversity of the TRBV genes and, in addition, identifies a substantial number of TRBV genes, predominantly from the larger subgroups, which are still absent from the genome assembly. The observed gene duplication within the bovine TRB locus has created a repertoire of phylogenetically diverse functional TRBV genes, which is substantially larger than that described for humans and mice. The analyses completed in this study reveal that, although the gene content and organization of the bovine TRB locus are broadly similar to that of humans and mice, multiple duplication events have led to a marked expansion in the number of TRB genes. Similar expansions in other ruminant TR loci suggest strong evolutionary pressures in this lineage have selected for the development of enlarged sets of TR genes that can contribute to diverse TR repertoires.
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