Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus.
Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus.
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DOI：
10.1186/1471-2164-15-994
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发表时间：
2014-11-19
期刊：
影响因子：
4.4
通讯作者：
Morrison WI
中科院分区：
文献类型：
--
作者：
Connelley TK;Degnan K;Longhi CW;Morrison WI
TRA/TRD基因座包含分别由αβ和γδ T细胞表达的TRA和TRD链的V（D）J体细胞重排基因。以往的研究表明，牛TRA/TRD基因座含有异常大量的TRAV/TRDV基因。在这项研究中，我们结合联合收割机基因组和转录分析，提供深入了解牛TRA/TRD基因座的进化发展和显着的TRAV/TRDV基因库。UMD 3.1组装的注释鉴定了371个TRAV/TRDV基因（分布在42个亚组中）、3个TRDJ、6个TRDD、62个TRAJ和单个TRAC和TRDC基因，其中大多数位于10号染色体的3.5Mb区域内。大多数TRAV/TRDV亚组具有多个成员，并且有几个经历了急剧的扩增，最值得注意的是TRDV 1（60个基因）。各个亚组内假基因比例的广泛变化表明，差异的“出生”和“死亡”率已被用于形成功能性牛TRAV/TRDV库，其在遗传学上与人类和小鼠不同。牛TRAV/TRDV基因库的扩增主要是通过一系列复杂的同源单元（含有多个基因的DNA区域）复制来实现的。频繁的共定位内的同源单位的基因的亚组与低和高的假基因比例表明，复制的同源单位驱动的进化选择，前者可能导致了“侧”的扩大后者。转录分析用于定义TRAV/TRDV亚组，可用于TRA和TRD链的重组，并证明表达的TRA和TRD库优先使用不同的亚组，表明TRA和TRD选择对TRAV/TRDV库的进化具有不同的影响。TRA和TRD选择都有助于牛TRAV/TRDV库的进化。然而，我们的数据表明，由于同源性单位重复，TRD选择TRDV 1亚组扩增可能大大有助于几个TRAV亚组的基因组扩增。这些数据表明，基因组和转录数据的整合可以提供一个更细致入微的欣赏进化动力学，导致显着扩大牛TRAV/TRDV剧目。本文的在线版本（doi：10.1186/1471-2164-15-994）包含补充材料，可供授权用户使用。
The TRA/TRD locus contains the genes for V(D)J somatic rearrangement of TRA and TRD chains expressed by αβ and γδ T cells respectively. Previous studies have demonstrated that the bovine TRA/TRD locus contains an exceptionally large number of TRAV/TRDV genes. In this study we combine genomic and transcript analysis to provide insights into the evolutionary development of the bovine TRA/TRD locus and the remarkable TRAV/TRDV gene repertoire. Annotation of the UMD3.1 assembly identified 371 TRAV/TRDV genes (distributed in 42 subgroups), 3 TRDJ, 6 TRDD, 62 TRAJ and single TRAC and TRDC genes, most of which were located within a 3.5 Mb region of chromosome 10. Most of the TRAV/TRDV subgroups have multiple members and several have undergone dramatic expansion, most notably TRDV1 (60 genes). Wide variation in the proportion of pseudogenes within individual subgroups, suggest that differential ‘birth’ and ‘death’ rates have been used to form a functional bovine TRAV/TRDV repertoire which is phylogenetically distinct from that of humans and mice. The expansion of the bovine TRAV/TRDV gene repertoire has predominantly been achieved through a complex series of homology unit (regions of DNA containing multiple gene) replications. Frequent co-localisation within homology units of genes from subgroups with low and high pseudogene proportions suggest that replication of homology units driven by evolutionary selection for the former may have led to a ‘collateral’ expansion of the latter. Transcript analysis was used to define the TRAV/TRDV subgroups available for recombination of TRA and TRD chains and demonstrated preferential usage of different subgroups by the expressed TRA and TRD repertoires, indicating that TRA and TRD selection have had distinct impacts on the evolution of the TRAV/TRDV repertoire. Both TRA and TRD selection have contributed to the evolution of the bovine TRAV/TRDV repertoire. However, our data suggest that due to homology unit duplication TRD selection for TRDV1 subgroup expansion may have substantially contributed to the genomic expansion of several TRAV subgroups. Such data demonstrate how integration of genomic and transcript data can provide a more nuanced appreciation of the evolutionary dynamics that have led to the dramatically expanded bovine TRAV/TRDV repertoire. The online version of this article (doi:10.1186/1471-2164-15-994) contains supplementary material, which is available to authorized users.
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