Abstract
BackgroundIn humans and mice ("γδ low species") less than 5% of the peripheral blood T lymphocytes are gamma/delta T cells, whereas in chicken and artiodactyls ("γδ high species") gamma/delta T cells represent about half of the T cells in peripheral blood. In cattle and sheep (Bovidae) two paralogous T cell receptor gamma loci (TRG1 and TRG2) have been found. TRG1 is located on 4q3.1, within a region of homology with the human TRG locus on chromosome 7, while TRG2 localizes on 4q2.2 and appears to be unique to ruminants. The purpose of this study was the sequencing of the genomic regions encompassing both loci in a "γδ high" organism and the analysis of their evolutionary history.ResultsWe obtained the contiguous genomic sequences of the complete sheep TRG1 and TRG2 loci gene repertoire and we performed cattle/sheep sequence analysis comparison using data available through public databases. Dot plot similarity matrix comparing the two sheep loci with each other has shown that variable (V), joining (J) and constant (C) genes have evolved through a series of duplication events involving either entire cassettes, each containing the basic V-J-J-C recombinational unit, or single V genes. The phylogenetic behaviour of the eight enhancer-like elements found in the sheep, compared with the single copy present in the human TRG locus, and evidence from concordant insertions of repetitive elements in all analyzed TRGJ blocks allowed us to infer an evolutionary scenario which highlights the genetic "flexibility" of this region and the duplication-driven evolution of gene cassettes. The strong similarity of the human and Bovidae intergenic J-J-C regions, which display an enhancer-like element at their 3' ends, further supports their key role in duplications.ConclusionWe propose that only duplications of entire J-J-C regions that possessed an enhancer-like element at their 3' end, and acquired at least one V segment at their 5' end, were selected and fixed as functional recombinational units.
Highlights
In humans and mice ("γδ low species") less than 5% of the peripheral blood T lymphocytes are gamma/delta T cells, whereas in chicken and artiodactyls ("γδ high species") gamma/delta T cells represent about half of the T cells in peripheral blood
In previous papers we described the entire ovine repertoire of the variable (V), joining (J) and constant (C) ovine genes and their organization in the TRG1 and TRG2 loci
The contiguous genomic sequence has allowed us to define the genomic structure of the sheep TRG1 and TRG2 loci
Summary
In humans and mice ("γδ low species") less than 5% of the peripheral blood T lymphocytes are gamma/delta T cells, whereas in chicken and artiodactyls ("γδ high species") gamma/delta T cells represent about half of the T cells in peripheral blood. T cell receptor variable domains are assembled during lymphocyte development from V, D, and J segments by V(D)J recombination. In developing T cells, specific molecular mechanisms target the recombinase activity to appropriate TR loci according to the allelic exclusion rule. This recombinase targeting at the level of the substrate locus, is known as recombinational accessibility [4,5,6]. In TRA/TRD and TRB loci a tightly correlation has been demonstrated between histone acetylation and V(D)J recombination and a mechanism for coupling enhancer activity with accessibility has been proposed [8,9]
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