The Comparative Genomics of Polyglutamine Repeats: Extreme Difference in the Codon Organization of Repeat-Encoding Regions Between Mammals and Drosophila |
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Authors: | M Mar Albà Mauro F Santibáñez-Koref John M Hancock |
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Institution: | (1) Wohl Virion Centre, Windeyer Institute of Medical Sciences, University College London, London W1P 6DB, U.K., GB;(2) Comparative Sequence Analysis Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, U.K., GB |
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Abstract: | Polyglutamine repeats within proteins are common in eukaryotes and are associated with neurological diseases in humans. Many
are encoded by tandem repeats of the codon CAG that are likely to mutate primarily by replication slippage. However, a recent
study in the yeast Saccharomyces cerevisiae has indicated that many others are encoded by mixtures of CAG and CAA which are less likely to undergo slippage. Here we
attempt to estimate the proportions of polyglutamine repeats encoded by slippage-prone structures in species currently the
subject of genome sequencing projects. We find a general excess over random expectation of polyglutamine repeats encoded by
tandem repeats of codons. We nevertheless find many repeats encoded by nontandem codon structures. Mammals and Drosophila display extreme opposite patterns. Drosophila contains many proteins with polyglutamine tracts but these are generally encoded by interrupted structures. These structures
may have been selected to be resistant to slippage. In contrast, mammals (humans and mice) have a high proportion of proteins
in which repeats are encoded by tandem codon structures. In humans, these include most of the triplet expansion disease genes.
Received: 17 August 2000 / Accepted: 20 November 2000 |
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Keywords: | : Glutamine repeats — Replication slippage — Comparative genome analysis — Repeat evolution — Triplet expansion diseases — Triplet repeats — Genome evolution |
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