66
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Multiple roles of the coding sequence 5′ end in gene expression regulation

      research-article
      1 , 2 , * , 1
      Nucleic Acids Research
      Oxford University Press

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The codon composition of the coding sequence's (ORF) 5′ end first few dozen codons is known to be distinct to that of the rest of the ORF. Various explanations for the unusual codon distribution in this region have been proposed in recent years, and include, among others, novel regulatory mechanisms of translation initiation and elongation. However, due to the fact that many overlapping regulatory signals are suggested to be associated with this relatively short region, its research is challenging. Here, we review the currently known signals that appear in this region, the theories related to the way they regulate translation and affect the organismal fitness, and the debates they provoke.

          Related collections

          Most cited references86

          • Record: found
          • Abstract: found
          • Article: not found

          The origins of genome complexity.

          Complete genomic sequences from diverse phylogenetic lineages reveal notable increases in genome complexity from prokaryotes to multicellular eukaryotes. The changes include gradual increases in gene number, resulting from the retention of duplicate genes, and more abrupt increases in the abundance of spliceosomal introns and mobile genetic elements. We argue that many of these modifications emerged passively in response to the long-term population-size reductions that accompanied increases in organism size. According to this model, much of the restructuring of eukaryotic genomes was initiated by nonadaptive processes, and this in turn provided novel substrates for the secondary evolution of phenotypic complexity by natural selection. The enormous long-term effective population sizes of prokaryotes may impose a substantial barrier to the evolution of complex genomes and morphologies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution.

            Strikingly consistent correlations between rates of coding-sequence evolution and gene expression levels are apparent across taxa, but the biological causes behind the selective pressures on coding-sequence evolution remain controversial. Here, we demonstrate conserved patterns of simple covariation between sequence evolution, codon usage, and mRNA level in E. coli, yeast, worm, fly, mouse, and human that suggest that all observed trends stem largely from a unified underlying selective pressure. In metazoans, these trends are strongest in tissues composed of neurons, whose structure and lifetime confer extreme sensitivity to protein misfolding. We propose, and demonstrate using a molecular-level evolutionary simulation, that selection against toxicity of misfolded proteins generated by ribosome errors suffices to create all of the observed covariation. The mechanistic model of molecular evolution that emerges yields testable biochemical predictions, calls into question the use of nonsynonymous-to-synonymous substitution ratios (Ka/Ks) to detect functional selection, and suggests how mistranslation may contribute to neurodegenerative disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Selection on codon bias.

              In a wide variety of organisms, synonymous codons are used with different frequencies, a phenomenon known as codon bias. Population genetic studies have shown that synonymous sites are under weak selection and that codon bias is maintained by a balance between selection, mutation, and genetic drift. It appears that the major cause for selection on codon bias is that certain preferred codons are translated more accurately and/or efficiently. However, additional and sometimes maybe even contradictory selective forces appear to affect codon usage as well. In this review, we discuss the current understanding of the ways in which natural selection participates in the creation and maintenance of codon bias. We also raise several open questions: (i) Is natural selection weak independently of the level of codon bias? It is possible that selection for preferred codons is weak only when codon bias approaches equilibrium and may be quite strong on genes with codon bias levels that are much lower and/or above equilibrium. (ii) What determines the identity of the major codons? (iii) How do shifts in codon bias occur? (iv) What is the exact nature of selection on codon bias? We discuss these questions in depth and offer some ideas on how they can be addressed using a combination of computational and experimental analyses.
                Bookmark

                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                09 January 2015
                12 December 2014
                12 December 2014
                : 43
                : 1
                : 13-28
                Affiliations
                [1 ]Department of Biomedical Engineering, the Engineering Faculty, Tel Aviv University, Tel Aviv, Israel
                [2 ]The Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel
                Author notes
                [* ]To whom correspondence should be addressed. Tel: +972 3 6405836; Fax: +972 3 6405836; Email: tamirtul@ 123456post.tau.ac.il
                Article
                10.1093/nar/gku1313
                4288200
                25505165
                0da6fee8-5eed-4879-bee8-63e819fdb805
                © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 December 2014
                : 06 November 2014
                : 30 August 2014
                Page count
                Pages: 16
                Categories
                Survey and Summary
                Custom metadata
                January 2015

                Genetics
                Genetics

                Comments

                Comment on this article