Transposable element fragments in protein-coding regions and their contributions to human functional proteins.
ABSTRACT Transposable elements (TEs) and their contributions to protein-coding regions are of particular interest. Here we searched for TE fragments in Homo sapiens at both the transcript and protein levels. We found evidence in support of TE exonization and its association with alternative splicing. Despite recent findings that long evolutionary times are required to incorporate TE into proteins, we found many functional proteins with translated TE cassettes derived from young TEs. Analyses of two Bcl-family proteins and Alu-encoded segments suggest the coding and functional potential of TE sequences.
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ABSTRACT: Among all of the many examples of mobile elements or "parasitic sequences" that affect the function of the human genome, this paper describes several examples of functioning genes whose sequences have been almost completely derived from mobile elements. There are many examples where the synthetic coding sequences of observed mRNA sequences are made up of mobile element sequences, to an extent of 80% or more of the length of the coding sequences. In the examples described here, the genes have named functions, and some of these functions have been studied. It appears that each of the functioning genes was originally formed from mobile elements and that in some process of molecular evolution a coding sequence was derived that could be translated into a protein that is of some importance to human biology. In one case (AD7C), the coding sequence is 99% made up of a cluster of Alu sequences. In another example, the gene BNIP3 coding sequence is 97% made up of sequences from an apparent human endogenous retrovirus. The Syncytin gene coding sequence appears to be made from an endogenous retrovirus envelope gene.Proceedings of the National Academy of Sciences 12/2004; 101(48):16825-30. · 9.74 Impact Factor
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ABSTRACT: Recent studies indicate that the initial classification of transposable elements (TEs) as 'useless', 'selfish' or 'junk' pieces of DNA is not an accurate one. TEs seem to have complex regulatory functions and contribute to the coding regions of many genes. Because this contribution had been documented only at transcript level, we searched for evidence that would also support the translation of TE cassettes. Our findings suggest that the proportion of proteins with TE-encoded fragments (approximately 0.1%), although probably underestimated, is much less than what the data at transcript level suggest (approximately 4%). In all cases, the TE cassettes are derived from old TEs, consistent with the idea that incorporation (exaptation) of TE fragments into functional proteins requires long evolutionary periods. We therefore argue that functional proteins are unlikely to contain TE cassettes derived from young TEs, the role of which is probably limited to regulatory functions.Trends in Genetics 06/2006; 22(5):260-7. · 9.77 Impact Factor
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ABSTRACT: To explore the possibility that an arbitrary sequence can evolve towards acquiring functional role when fused with other pre-existing protein modules, we replaced the D2 domain of the fd-tet phage genome with the soluble random polypeptide RP3-42. The replacement yielded an fd-RP defective phage that is six-order magnitude lower infectivity than the wild-type fd-tet phage. The evolvability of RP3-42 was investigated through iterative mutation and selection. Each generation consists of a maximum of ten arbitrarily chosen clones, whereby the clone with highest infectivity was selected to be the parent clone of the generation that followed. The experimental evolution attested that, from an initial single random sequence, there will be selectable variation in a property of interest and that the property in question was able to improve over several generations. fd-7, the clone with highest infectivity at the end of the experimental evolution, showed a 240-fold increase in infectivity as compared to its origin, fd-RP. Analysis by phage ELISA using anti-M13 antibody and anti-T7 antibody revealed that about 37-fold increase in the infectivity of fd-7 was attributed to the changes in the molecular property of the single polypeptide that replaced the D2 domain of the g3p protein. This study therefore exemplifies the process of a random polypeptide generating a functional role in rejuvenating the infectivity of a defective bacteriophage when fused to some preexisting protein modules, indicating that an arbitrary sequence can evolve toward acquiring a functional role. Overall, this study could herald the conception of new perspective regarding primordial polypeptides in the field of molecular evolution.Journal of Molecular Evolution 03/2003; 56(2):162-8. · 2.15 Impact Factor