Data from: Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus

Background: 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. Results: 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. Conclusion: 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.背景：T细胞受体α链（TRA）/δ链（TRD）基因座分别包含编码αβ和γδ T细胞所表达的TRA链与TRD链的V(D)J体细胞重排相关基因。既往研究已证实，牛的TRA/TRD基因座含有数量极多的T细胞受体α/δ可变区（TRAV/TRDV）基因。本研究结合基因组分析与转录分析，解析牛TRA/TRD基因座的演化历程及其独特的TRAV/TRDV基因库。 结果：对UMD3.1基因组组装版本的注释分析共鉴定出371个TRAV/TRDV基因（分布于42个亚家族）、3个T细胞受体δ链连接基因（TRDJ）、6个T细胞受体δ链多样性基因（TRDD）、62个T细胞受体α链连接基因（TRAJ）以及单个T细胞受体α链恒定区基因（TRAC）和单个T细胞受体δ链恒定区基因（TRDC），其中绝大多数位于10号染色体的3.5 Mb区域内。多数TRAV/TRDV亚家族拥有多个基因拷贝，部分亚家族发生了显著的基因扩张，其中尤以TRDV1亚家族最为突出，共包含60个基因。各亚家族内假基因占比存在极大差异，提示差异化的基因诞生与消亡速率塑造了功能完整的牛TRAV/TRDV基因库，该基因库在系统发育层面与人类和小鼠的同类基因库存在显著差异。牛TRAV/TRDV基因库的扩张主要通过一系列复杂的同源单元（homology unit，包含多个基因的DNA区域）复制事件实现。假基因占比高低不同的亚家族基因频繁共定位于同源单元内，这提示针对假基因占比较低亚家族的进化选择所驱动的同源单元复制，可能间接导致了假基因占比较高亚家族的"附带"扩张。本研究通过转录分析明确了可用于TRA和TRD链重排的TRAV/TRDV亚家族，并证实表达的TRA和TRD受体库对不同亚家族存在偏好性使用，这表明TRA和TRD的选择压力对TRAV/TRDV基因库的演化产生了截然不同的影响。 结论：TRA与TRD的选择压力均参与塑造了牛TRAV/TRDV基因库的演化历程。然而本研究数据显示，由于同源单元复制事件，针对TRDV1亚家族扩张的TRD选择压力，可能在很大程度上推动了多个TRAV亚家族的基因组扩张。此类研究结果证实，整合基因组与转录组数据能够更为细致地解析驱动牛TRAV/TRDV基因库显著扩张的演化动力学机制。