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Transposable elements have contributed to thousands of human proteins.

ABSTRACT: This is a report of many distant but significant protein sequence relationships between human proteins and transposable elements (TEs). The libraries of human repeated sequences contain the DNA sequences of many TEs. These were translated in all reading frames, ignoring stop codons, and were used as amino acid sequence probes to search with BLASTP for similar sequences in a library of 25,193 human proteins. The probes show regions of significant amino acid sequence similarity to 1,950 different human genes, with an expectation of <10(-3). In comparison with previous REPEATMASKER (Institute for Systems Biology, Seattle) studies, these probes detect many more TE sequences in more human coding sequences with greater length than previous work using DNA sequences. If the criterion is opened, very many matches are found occurring on 4,653 different genes after correction for the number seen with random amino acid sequence probes. The processes that led to these extensive sets of sequence relationships between TEs and coding sequences of human genes have been a major source of variation and novel genes during evolution. This paper lists the number of sequence similarities seen by amino acid sequence comparison, which is surely an underestimate of the actual number of significant relationships. It appears that many of these are the result of past events of duplication of genes or gene regions, rather than a direct result of TE insertion. This report of observable relationships leaves to the future the functional implications as well as the detection of the events of TE insertion.

SUBMITTER: Britten R

PROVIDER: S-EPMC1413650 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature

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Transposable elements have contributed to thousands of human proteins.

Britten Roy R

Proceedings of the National Academy of Sciences of the United States of America 20060127 6

This is a report of many distant but significant protein sequence relationships between human proteins and transposable elements (TEs). The libraries of human repeated sequences contain the DNA sequences of many TEs. These were translated in all reading frames, ignoring stop codons, and were used as amino acid sequence probes to search with BLASTP for similar sequences in a library of 25,193 human proteins. The probes show regions of significant amino acid sequence similarity to 1,950 different ...[more]

PMID: 16443682

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Project description:BACKGROUND:Transposition is disruptive in nature and, thus, it is imperative for host genomes to evolve mechanisms that suppress the activity of transposable elements (TEs). At the same time, transposition also provides diverse sequences that can be exapted by host genomes as functional elements. These notions form the basis of two competing hypotheses pertaining to the role of epigenetic modifications of TEs in eukaryotic genomes: the genome defense hypothesis and the exaptation hypothesis. To date, all available evidence points to the genome defense hypothesis as the best explanation for the biological role of TE epigenetic modifications. RESULTS:We evaluated several predictions generated by the genome defense hypothesis versus the exaptation hypothesis using recently characterized epigenetic histone modification data for the human genome. To this end, we mapped chromatin immunoprecipitation sequence tags from 38 histone modifications, characterized in CD4+ T cells, to the human genome and calculated their enrichment and depletion in all families of human TEs. We found that several of these families are significantly enriched or depleted for various histone modifications, both active and repressive. The enrichment of human TE families with active histone modifications is consistent with the exaptation hypothesis and stands in contrast to previous analyses that have found mammalian TEs to be exclusively repressively modified. Comparisons between TE families revealed that older families carry more histone modifications than younger ones, another observation consistent with the exaptation hypothesis. However, data from within family analyses on the relative ages of epigenetically modified elements are consistent with both the genome defense and exaptation hypotheses. Finally, TEs located proximal to genes carry more histone modifications than the ones that are distal to genes, as may be expected if epigenetically modified TEs help to regulate the expression of nearby host genes. CONCLUSIONS:With a few exceptions, most of our findings support the exaptation hypothesis for the role of TE epigenetic modifications when vetted against the genome defense hypothesis. The recruitment of epigenetic modifications may represent an additional mechanism by which TEs can contribute to the regulatory functions of their host genomes.

Dataset Information

Transposable elements have contributed to thousands of human proteins.

Publications

Transposable elements have contributed to thousands of human proteins.

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