Evolutionary fate of retroposed gene copies in the human genome

Abstract

Given that retroposed copies of genes are presumed to lack the regulatory elements required for their expression, retroposition has long been considered a mechanism without functional relevance. However, through an in silico assay for transcriptional activity, we identify here >1,000 transcribed retrocopies in the human genome, of which at least Ϸ120 have evolved into bona fide genes. Among these, Ϸ50 retrogenes have evolved functions in testes, more than half of which were recruited as functional autosomal counterparts of X-linked genes during spermatogenesis. Generally, retrogenes emerge ''out of the testis,'' because they are often initially transcribed in testis and later evolve stronger and sometimes more diverse spatial expression patterns. We find a significant excess of transcribed retrocopies close to other genes or within introns, suggesting that retrocopies can exploit the regulatory elements and͞or open chromatin of neighboring genes to become transcribed. In direct support of this hypothesis, we identify 36 retrocopy-host gene fusions, including primate-specific chimeric genes. Strikingly, 27 intergenic retrogenes have acquired untranslated exons de novo during evolution to achieve high expression levels. Notably, our screen for highly transcribed retrocopies also uncovered a retrogene linked to a human recessive disorder, gelatinous drop-like corneal dystrophy, a form of blindness. These functional implications for retroposition notwithstanding, we find that the insertion of retrocopies into genes is generally deleterious, because it may interfere with the transcription of host genes. Our results demonstrate that natural selection has been fundamental in shaping the retrocopy repertoire of the human genome.origin of new genes ͉ retroposition ͉ transcription

Extensive Structural Renovation of Retrogenes in the Evolution of the Populus Genome

“…In other words, the majority of retrocopies in this dicotyledonous species was associated with significant functionality. This is in sharp contrast to the human genome, in which only 16% of retrocopies are potentially functional, while the remaining majority seems to be functionless (Vinckenbosch et al, 2006).…”

“…gence time of these species (Tuskan et al, 2006), their ages should be younger than 100 million years. This gives a rate of structural innovation of around 0.1 events per million years per genome, comparable with the rate of retrogene chimerization in hominoid lineages (0.14; Marques et al, 2005;Vinckenbosch et al, 2006).…”

Pollen-Specific Activation of Arabidopsis Retrogenes Is Associated with Global Transcriptional Reprogramming

“…Pollen-specific transcription of Arabidopsis retrogenes was unanticipated and is analogous to retrogene transcription in animal spermatocytes (Marques et al, 2005;Vinckenbosch et al, 2006;Bai et al, 2008). Although the molecular nature of this specific transcription is so far unknown, two explanatory models have been proposed in animals (Kaessmann et al, 2009).…”

“…In flies and mammals, many retrogenes show testis-specific transcription (Marques et al, 2005;Vinckenbosch et al, 2006;Bai et al, 2008). This pattern is intriguing, and several explanatory models have been proposed (reviewed in Kaessmann et al, 2009;Kaessmann, 2010).…”

Transposable elements as drivers of genomic and biological diversity in vertebrates

“…Lineage-specific gene duplicates can also be generated through reverse transcription of cellular genes, resulting in intronless cDNA copies called retrogenes. Whereas most of these genes evolved as pseudogenes, some copies can acquire a new function (Vinckenbosch et al 2006). About 200 and 300 retrogenes have been formed in the human and chimpanzee lineages, respectively, after split from the last common ancestor (Chimpanzee Sequencing and Analysis Consortium 2005).…”