Evolutionary origin and functions of retrogene introns.
ABSTRACT Retroposed genes (retrogenes) originate via the reverse transcription of mature messenger RNAs from parental source genes and are therefore usually devoid of introns. Here, we characterize a particular set of mammalian retrogenes that acquired introns upon their emergence and thus represent rare cases of intron gain in mammals. We find that although a few retrogenes evolved introns in their coding or 3' untranslated regions (untranslated region, UTR), most introns originated together with untranslated exons in the 5' flanking regions of the retrogene insertion site. They emerged either de novo or through fusions with 5' UTR exons of host genes into which the retrogenes inserted. Generally, retrogenes with introns display high transcription levels and show broader spatial expression patterns than other retrogenes. Our experimental expression analyses of individual intron-containing retrogenes show that 5' UTR introns may indeed promote higher expression levels, at least in part through encoded regulatory elements. By contrast, 3' UTR introns may lead to downregulation of expression levels via nonsense-mediated decay mechanisms. Notably, the majority of retrogenes with introns in their 5' flanks depend on distant, sometimes bidirectional CpG dinucleotide-enriched promoters for their expression that may be recruited from other genes in the genomic vicinity. We thus propose a scenario where the acquisition of new 5' exon-intron structures was directly linked to the recruitment of distant promoters by these retrogenes, a process potentially facilitated by the presence of proto-splice sites in the genomic vicinity of retrogene insertion sites. Thus, the primary role and selective benefit of new 5' introns (and UTR exons) was probably initially to span the often substantial distances to potent CpG promoters driving retrogene transcription. Later in evolution, these introns then obtained additional regulatory roles in fine tuning retrogene expression levels. Our study provides novel insights regarding mechanisms underlying the origin of new introns, the evolutionary relevance of intron gain, and the origin of new gene promoters.
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ABSTRACT: Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here we presented an evolutionary analysis of the CTAGE (cutaneous T cell lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multi-exon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats (LTRs). Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution.Molecular Biology and Evolution 06/2014; 31(9). DOI:10.1093/molbev/msu188 · 14.31 Impact Factor
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ABSTRACT: Retrogenes are duplicated genes generated via retro-position, which were conventionally believed to contain no introns. However, emerging data showed that a significant number of retrogenes do have introns. Thus, these genes represent an attractive system to study how new genes evolve exon–intron structure. Comparison between par-ental genes and retrogenes revealed that retrogenes mainly evolve chimeric structures by fusing with local host genes or recruiting pre-existing intergenic sequences. Additionally, retrogenes could gain introns by inheriting introns of parental genes or by transforming parental exonic sequences. The functional necessity on intron gain in retrogenes remains largely elusive although limited data suggest that newborn introns play regulatory roles, enable exon shuffling and alternative splicing. Accumulation of population genomic data may help to understand which evolutionary force shapes the fixation of introns in both retrogenes and de novo originated genes given the same intron birth process acts on both type of new genes.
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ABSTRACT: The study of retrogenes is not only a relevant topic in the evolutionary analysis of gene origin, but also a way of performing genome-wide studies on possible correlations between different species. Existing literature on retrogene detection however, takes advantage of detailed annotations of certain genomes, therefore restricting their domain of application. This is what motivated the development of a generalized pipeline for retrogene detection. We detail the steps and main concepts in building this robust pipeline that, given the cDNA library and the genome database for a specific species, identifies retrogenes. Apart from being built genome-independent, our pipeline can also identify chimeric retrogenes. We also present possible improvements in light of the difficulties encountered in developing such a pipeline.