Dataset Information

Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus.

ABSTRACT: The TRA/TRD locus contains the genes for V(D)J somatic rearrangement of TRA and TRD chains expressed by ?? and ?? 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.

SUBMITTER: Connelley TK

PROVIDER: S-EPMC4289303 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus.

Connelley Timothy K TK Degnan Kathryn K Longhi Cassandra W CW Morrison W Ivan WI

BMC genomics 20141119

<h4>Background</h4>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.<h4>Results</h4>Annotation of the UMD ...[more]

PMID: 25408163

Similar Datasets

Project description:BACKGROUND:In mammals, T cells develop along two discrete pathways characterized by expression of either the ?? or the ?? T cell receptors. Human and mouse display a low peripheral blood ?? T cell percentage ("?? low species") while sheep, bovine and pig accounts for a high proportion of ?? T lymphocytes ("?? high species"). While the T cell receptor alpha (TRA) and delta (TRD) genes and the genomic organization of the TRA/TRD locus has been determined in human and mouse, this information is still poorly known in artiodactyl species, such as sheep. RESULTS:The analysis of the current Ovis aries whole genome assembly, Oar_v3.1, revealed that, as in the other mammalian species, the sheep TRD locus is nested within the TRA locus. In the most 5' part the TRA/TRD locus contains TRAV genes which are intermingled with TRDV genes, then TRD genes which include seven TRDD, four TRDJ genes, one TRDC and a single TRDV gene with an inverted transcriptional orientation, and finally in the most 3' part, the TRA locus is completed by 61 TRAJ genes and one TRAC gene. Comparative sequence and analysis and annotation led to the identification of 66 TRAV genes assigned to 34 TRAV subgroups and 25 TRDV genes belonging to the TRDV1 subgroup, while one gene was found for each TRDV2, TRDV3 and TRDV4 subgroups. Multiple duplication events within several TRAV subgroups have generated the sheep TRAV germline repertoire, which is substantially larger than the human one. A significant proportion of these TRAV gene duplications seems to have occurred simultaneously with the amplification of the TRDV1 subgroup genes. This dynamic of expansion has also generated novel multigene subgroups, which are species-specific. Ovis aries TRA and TRD genes identified in this study were assigned IMGT definitive or temporary names and were approved by the IMGT/WHO-IUIS nomenclature committee. The completeness of the genome assembly in the 3' part of the locus has allowed us to interpret rearranged CDR3 of cDNA from both TRA and TRD chain repertoires. The involvement of one up to four TRDD genes into a single transcript makes the potential sheep TRD chain much larger than any known TR chain repertoire. CONCLUSIONS:The sheep genome, as the bovine genome, contains a large and diverse repertoire of TRA and TRD genes when compared to the "?? T cell low" species genomes. The composition and length of the rearranged CDR3 in TRD V-delta domains influence the three-dimensional configuration of the antigen-combining site thus suggesting that in ruminants, ?? T cells play a more important and specific role in immune recognition.

Project description:BackgroundDiverse 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.ResultsThe TRB locus in the third bovine genome assembly is distributed over 5 scaffolds, extending to approximately 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.ConclusionThe 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.

Project description:BackgroundObtaining phylogenomic data for enigmatic taxa is essential to achieve a better understanding of animal evolution. Dicyemids have long fascinated biologists because of their highly simplified body organization, but their life-cycles remain poorly known. Based on the discovery of the dicyemid DoxC gene, which encodes a spiralian peptide, it has been proposed that dicyemids are members of the Spiralia. Other studies have suggested that dicyemids may have closer affinities to mollusks and annelids. However, the phylogenetic position of dicyemids has remained a matter of debate, leading to an ambiguous picture of spiralian evolution.ResultsIn the present study, newly sequenced transcriptomic data from Dicyema japonicum were complemented with published transcriptomic data or predicted gene models from 29 spiralian, ecdysozoan, and deuterostome species, generating a dataset (Dataset 1) for phylogenomic analyses, which contains 348 orthologs and 58,124 amino acids. In addition to this dataset, to eliminate systematic errors, two additional sub-datasets were created by removing compositionally heterogeneous or rapidly evolving sites and orthologs from Dataset 1, which may cause compositional heterogeneity and long-branch attraction artifacts. Maximum likelihood and Bayesian inference analyses both placed Dicyema japonicum (Dicyemida) in a clade with Intoshia linei (Orthonectida) with strong statistical support. Furthermore, maximum likelihood analyses placed the Dicyemida + Orthonectida clade within the Gastrotricha, while in Bayesian inference analyses, this clade is sister group to the clade of Gastrotricha + Platyhelminthes.ConclusionsWhichever the case, in all analyses, Dicyemida, Orthonectida, Gastrotricha, and Platyhelminthes constitute a monophyletic group that is a sister group to the clade of Mollusca + Annelida. Based on present phylogenomic analyses, dicyemids display close affinity to orthonectids, and they may share a common ancestor with gastrotrichs and platyhelminths, rather than with mollusks and annelids. Regarding spiralian phylogeny, the Gnathifera forms the sister group to the Rouphozoa and Lophotrochozoa, as has been suggested by previous studies; thus our analysis supports the traditional acoeloid-planuloid hypothesis of a nearly microscopic, non-coelomate common ancestor of spiralians.

Project description:The fungal kingdom has provided advances in our ability to identify biosynthetic gene clusters (BGCs) and to examine how gene composition of BGCs evolves across species and genera. However, little is known about the evolution of specific BGC regulators that mediate how BGCs produce secondary metabolites (SMs). A bioinformatics search for conservation of the Aspergillus fumigatus xanthocillin BGC revealed an evolutionary trail of xan-like BGCs across Eurotiales species. Although the critical regulatory and enzymatic genes were conserved in Penicillium expansum, overexpression (OE) of the conserved xan BGC transcription factor (TF) gene, PexanC, failed to activate the putative xan BGC transcription or xanthocillin production in P. expansum, in contrast to the role of AfXanC in A. fumigatus. Surprisingly, OE::PexanC was instead found to promote citrinin synthesis in P. expansum via trans induction of the cit pathway-specific TF, ctnA, as determined by cit BGC expression and chemical profiling of ctnA deletion and OE::PexanC single and double mutants. OE::AfxanC results in significant increases of xan gene expression and metabolite synthesis in A. fumigatus but had no effect on either xanthocillin or citrinin production in P. expansum. Bioinformatics and promoter mutation analysis led to the identification of an AfXanC binding site, 5'-AGTCAGCA-3', in promoter regions of the A. fumigatus xan BGC genes. This motif was not in the ctnA promoter, suggesting a different binding site of PeXanC. A compilation of a bioinformatics examination of XanC orthologs and the presence/absence of the 5'-AGTCAGCA-3' binding motif in xan BGCs in multiple Aspergillus and Penicillium spp. supports an evolutionary divergence of XanC regulatory targets that we speculate reflects an exaptation event in the Eurotiales. IMPORTANCE Fungal secondary metabolites (SMs) are an important source of pharmaceuticals on one hand and toxins on the other. Efforts to identify the biosynthetic gene clusters (BGCs) that synthesize SMs have yielded significant insights into how variation in the genes that compose BGCs may impact subsequent metabolite production within and between species. However, the role of regulatory genes in BGC activation is less well understood. Our finding that the bZIP transcription factor XanC, located in the xanthocillin BGC of both Aspergillus fumigatus and Penicillium expansum, has functionally diverged to regulate different BGCs in these two species emphasizes that the diversification of BGC regulatory elements may sometimes occur through exaptation, which is the co-option of a gene that evolved for one function to a novel function. Furthermore, this work suggests that the loss/gain of transcription factor binding site targets may be an important mediator in the evolution of secondary-metabolism regulatory elements.

Project description:BackgroundThe bottlenose dolphin (Tursiops truncatus) is a mammal that belongs to the Cetartiodactyla and have lived in marine ecosystems for nearly 60 millions years. Despite its popularity, our knowledge about its adaptive immunity and evolution is very limited. Furthermore, nothing is known about the genomics and evolution of dolphin antigen receptor immunity.ResultsHere we report a evolutionary and expression study of Tursiops truncatus T cell receptor gamma (TRG) and alpha/delta (TRA/TRD) genes. We have identified in silico the TRG and TRA/TRD genes and analyzed the relevant mature transcripts in blood and in skin from four subjects. The dolphin TRG locus is the smallest and simplest of all mammalian loci as yet studied. It shows a genomic organization comprising two variable (V1 and V2), three joining (J1, J2 and J3) and a single constant (C), genes. Despite the fragmented nature of the genome assemblies, we deduced the TRA/TRD locus organization, with the recent TRDV1 subgroup genes duplications, as it is expected in artiodactyls. Expression analysis from blood of a subject allowed us to assign unambiguously eight TRAV genes to those annotated in the genomic sequence and to twelve new genes, belonging to five different subgroups. All transcripts were productive and no relevant biases towards TRAV-J rearrangements are observed. Blood and skin from four unrelated subjects expression data provide evidence for an unusual ratio of productive/unproductive transcripts which arise from the TRG V-J gene rearrangement and for a "public" gamma delta TR repertoire. The productive cDNA sequences, shared both in the same and in different individuals, include biases of the TRGV1 and TRGJ2 genes. The high frequency of TRGV1-J2/TRDV1- D1-J4 productive rearrangements in dolphins may represent an interesting oligo-clonal population comparable to that found in human with the TRGV9- JP/TRDV2-D-J T cells and in primates.ConclusionsAlthough the features of the TRG and TRA/TRD loci organization reflect those of the so far examined artiodactyls, genomic results highlight in dolphin an unusually simple TRG locus. The cDNA analysis reveal productive TRA/TRD transcripts and unusual ratios of productive/unproductive TRG transcripts. Comparing multiple different individuals, evidence is found for a "public" gamma delta TCR repertoire thus suggesting that in dolphins as in human the gamma delta TCR repertoire is accompanied by selection for public gamma chain.

Dataset Information

Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus.

Publications

Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets