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Polyglutamine repeats are associated to specific sequence biases that are conserved among eukaryotes.

Abstract : Nine human neurodegenerative diseases, including Huntington's disease and several spinocerebellar ataxia, are associated to the aggregation of proteins comprising an extended tract of consecutive glutamine residues (polyQs) once it exceeds a certain length threshold. This event is believed to be the consequence of the expansion of polyCAG codons during the replication process. This is in apparent contradiction with the fact that many polyQs-containing proteins remain soluble and are encoded by invariant genes in a number of eukaryotes. The latter suggests that polyQs expansion and/or aggregation might be counter-selected through a genetic and/or protein context. To identify this context, we designed a software that scrutinize entire proteomes in search for imperfect polyQs. The nature of residues flanking the polyQs and that of residues other than Gln within polyQs (insertions) were assessed. We discovered strong amino acid residue biases robustly associated to polyQs in the 15 eukaryotic proteomes we examined, with an over-representation of Pro, Leu and His and an under-representation of Asp, Cys and Gly amino acid residues. These biases are conserved amongst unrelated proteins and are independent of specific functional classes. Our findings suggest that specific residues have been co-selected with polyQs during evolution. We discuss the possible selective pressures responsible of the observed biases.
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https://hal.archives-ouvertes.fr/hal-01183156
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Submitted on : Thursday, August 6, 2015 - 2:50:07 PM
Last modification on : Thursday, July 11, 2019 - 2:10:07 PM

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Matteo Ramazzotti, Elodie Monsellier, Choumouss Kamoun, Donatella Degl'Innocenti, Ronald Melki. Polyglutamine repeats are associated to specific sequence biases that are conserved among eukaryotes.. PLoS ONE, Public Library of Science, 2011, 7 (2), pp.e30824. ⟨10.1371/journal.pone.0030824⟩. ⟨hal-01183156⟩

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