Computational characterization of multiple Gag-like human proteins

Campillos, Mónica; Doerks, Tobias; Shah, Parantu K.; Bork, Peer

doi:10.1016/j.tig.2006.09.006

Cited by 142 publications

(197 citation statements)

References 21 publications

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“…The genomes of humans and other mammals have incorporated a significant number of genes derived from retroelements and retroviruses by a process called molecular domestication (44). The evolution of the placenta is one process that has utilized the functionalities of retroelements and retroviruses.…”

Section: Discussionmentioning

confidence: 99%

Mammalian Gene PEG10 Expresses Two Reading Frames by High Efficiency –1 Frameshifting in Embryonic-associated Tissues

Clark¹,

Jänicke²,

Gottesbühren³

et al. 2007

Journal of Biological Chemistry

113

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Paternally expressed gene 10 (PEG10) is a mammalian gene that is essential for embryonic development in mice. The gene contains two overlapping open reading frames (ORF1 and ORF2) and is derived from a retroelement that acquired a cellular function. It is not known if both reading frames are required for PEG10 function. Synthesis of ORF2 would be possible only if programmed ؊1 frameshifting occurred during ORF1 translation. In this study the frameshifting activity of PEG10 was analyzed in vivo, and a potential role for ORF2 was investigated. Phylogenetic analysis demonstrated that PEG10 is highly conserved in therian mammals, with all species retaining the elements necessary for frameshifting as well as functional motifs in each ORF. The frameshift site of PEG10 was highly active in cultured cells and produced the ORF1-2 protein. In mice, endogenous ORF1 and an ORF1-2 frameshift protein were detected in the developing placenta and amniotic membrane from 9.5 days post-coitus through to term with a very high frameshift efficiency (>60%). Mutagenesis of the active site motif of a putative protease within ORF2 showed that this enzyme is active and participates in post-translational processing of PEG10 ORF1-2. Both PEG10 proteins were also detected in first trimester human placenta. By contrast, neither protein expression nor frameshifting was detected in adult mouse tissues. These studies imply that the ORF1-2 protein, synthesized utilizing the most efficient ؊1 frameshift mechanism yet documented in vivo, will have an essential function that is intrinsic to the importance of PEG10 in mammals.

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Section: Discussionmentioning

confidence: 99%

Mammalian Gene PEG10 Expresses Two Reading Frames by High Efficiency –1 Frameshifting in Embryonic-associated Tissues

Clark¹,

Jänicke²,

Gottesbühren³

et al. 2007

Journal of Biological Chemistry

113

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“…The critical role for Peg10 in the origin of the placenta, together with the DNA methylation characteristics of the locus in marsupials, suggests that silencing of exogenous DNA after retrotransposition was an essential step in the evolution of the epigenetic systems involved in imprinted gene expression in mammals. (63) Campillos et al (64) identified 85 gag genes in humans, encoding 103 protein isoforms, suggesting that Peg10 and Rtl1 represent the tip of the iceberg with respect to gag gene domestication. In addition, genes recruited from a second retro-element type contribute to fusogenic and immunosuppressive properties of the placenta.…”

Section: Transposable Elements Drive the Evolution Of Epigenetic Silementioning

confidence: 99%

Transposable elements and an epigenetic basis for punctuated equilibria

2009

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Evolution is frequently concentrated in bursts of rapid morphological change and speciation followed by longterm stasis. We propose that this pattern of punctuated equilibria results from an evolutionary tug-of-war between host genomes and transposable elements (TEs) mediated through the epigenome. According to this hypothesis, epigenetic regulatory mechanisms (RNA interference, DNA methylation and histone modifications) maintain stasis by suppressing TE mobilization. However, physiological stress, induced by climate change or invasion of new habitats, disrupts epigenetic regulation and unleashes TEs. With their capacity to drive non-adaptive host evolution, mobilized TEs can restructure the genome and displace populations from adaptive peaks, thus providing an escape from stasis and generating genetic innovations required for rapid diversification. This ''epi-transposon hypothesis'' can not only explain macroevolutionary tempo and mode, but may also resolve other long-standing controversies, such as Wright's shifting balance theory, Mayr's peripheral isolates model, and McClintock's view of genome restructuring as an adaptive response to challenge.

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“…12). More than 100 human genes have been recognized as probably derived from transposons (13,14). The best studied example is the RAG1 gene that evolved from the Transib superfamily of DNA transposons (15) and that, together with RAG2, carries out V(D)J recombination, a site-directed DNA rearrangement of Ig gene segments in vertebrates (16).…”

mentioning

confidence: 99%