Human coding synonymous single nucleotide polymorphisms at ramp regions of mRNA translation

PLoS One. 2013;8(3):e59706. doi: 10.1371/journal.pone.0059706. Epub 2013 Mar 19.

Abstract

According to the ramp model of mRNA translation, the first 50 codons favor rare codons and have slower speed of translation. This study aims to detect translational selection on coding synonymous single nucleotide polymorphisms (sSNP) to support the ramp theory. We investigated fourfold degenerate site (FFDS) sSNPs with A ↔ G or C ↔ T substitutions in human genome for distribution bias of synonymous codons (SC), grouped by CpG or non-CpG sites. Distribution bias of sSNPs between the 3(rd) ~50(th) codons and the 51(st) ~ remainder codons at non-CpG sites were observed. In the 3(rd) ~50(th) codons, G → A sSNPs at non-CpG sites are favored than A → G sSNPs [P = 2.89 × 10(-3)], and C → T at non-CpG sites are favored than T → C sSNPs [P = 8.50 × 10(-3)]. The favored direction of SC usage change is from more frequent SCs to less frequent SCs. The distribution bias is more obvious in synonymous substitutions CG(G → A), AC(C → T), and CT(C → T). The distribution bias of sSNPs in human genome, i.e. frequent SCs to less frequent SCs is favored in the 3(rd) ~50(th) codons, indicates translational selection on sSNPs in the ramp regions of mRNA templates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Codon / genetics*
  • Genome, Human / genetics*
  • Humans
  • Models, Genetic*
  • Point Mutation / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Protein Biosynthesis / genetics*
  • Protein Biosynthesis / physiology
  • RNA, Messenger / genetics*
  • Selection, Genetic*

Substances

  • Codon
  • RNA, Messenger

Grant support

L.Q. holds a fellowship from Eli Lilly Canada, and H.Q.Q. is supported by intramural funding from the University of Texas School of Public Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.