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Preventing Dangerous Nonsense: Selection for Robustness to Transcriptional Error in Human Genes

Summary: Preventing Dangerous Nonsense: Selection for
Robustness to Transcriptional Error in Human Genes
Brian P. Cusack1,2
*, Peter F. Arndt1
, Laurent Duret3
, Hugues Roest Crollius2
1 Max Planck Institute for Molecular Genetics, Department of Computational Molecular Biology, Berlin, Germany, 2 Institut de Biologie de l'Ecole Normale Supe´rieure
(IBENS), CNRS UMR8197, INSERM U1024, Paris, France, 3 Universite´ de Lyon, Universite´ Lyon 1, CNRS, UMR 5558, Laboratoire de Biome´trie et Biologie Evolutive,
Villeurbanne, France
Nonsense Mediated Decay (NMD) degrades transcripts that contain a premature STOP codon resulting from
mistranscription or missplicing. However NMD's surveillance of gene expression varies in efficiency both among and
within human genes. Previous work has shown that the intron content of human genes is influenced by missplicing events
invisible to NMD. Given the high rate of transcriptional errors in eukaryotes, we hypothesized that natural selection has
promoted a dual strategy of ``prevention and cure'' to alleviate the problem of nonsense transcriptional errors. A prediction
of this hypothesis is that NMD's inefficiency should leave a signature of ``transcriptional robustness'' in human gene
sequences that reduces the frequency of nonsense transcriptional errors. For human genes we determined the usage of
``fragile'' codons, prone to mistranscription into STOP codons, relative to the usage of ``robust'' codons that do not generate
nonsense errors. We observe that single-exon genes have evolved to become robust to mistranscription, because they show
a significant tendency to avoid fragile codons relative to robust codons when compared to multi-exon genes. A similar


Source: Arndt, Peter - Max-Planck-Institut für molekulare Genetik
Spang, Rainer - Computational Molecular Biology Group, Max-Planck-Institut für molekulare Genetik


Collections: Biology and Medicine; Biotechnology; Computer Technologies and Information Sciences; Physics