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Exploration for Functional Nucleotide Sequence Candidates within Coding Regions of Mammalian Genes

By Rumiko Suzuki and Naruya Saitou

Abstract

The primary role of a protein coding gene is to encode amino acids. Therefore, synonymous sites of codons, which do not change the encoded amino acid, are regarded as evolving neutrally. However, if a certain region of a protein coding gene contains a functional nucleotide element (e.g. splicing signals), synonymous sites in the region may have selective pressure. The existence of such elements would be detected by searching regions of low nucleotide substitution. We explored invariant nucleotide sequences in 10 790 orthologous genes of six mammalian species (Homo sapiens, Macaca mulatta, Mus musculus, Rattus norvegicus, Bos taurus, and Canis familiaris), and extracted 4150 sequences whose conservation is significantly stronger than other regions of the gene and named them significantly conserved coding sequences (SCCSs). SCCSs are observed in 2273 genes. The genes are mainly involved with development, transcriptional regulation, and the neurons, and are expressed in the nervous system and the head and neck organs. No strong influence of conventional factors that affect synonymous substitution was observed in SCCSs. These results imply that SCCSs may have double function as nucleotide element and protein coding sequence and retained in the course of mammalian evolution

Topics: Full Papers
Publisher: Oxford University Press
OAI identifier: oai:pubmedcentral.nih.gov:3111233
Provided by: PubMed Central

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Citations

  1. (1991). An analysis of codon usage in mammals: selection or mutation bias?
  2. (2008). An ultraconserved Hox-Pbx responsive element resides in the coding sequence of Hoxa2 and is active in rhombomere 4,
  3. (2004). Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes,
  4. (1994). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
  5. (1991). Codon bias and gene expression,
  6. (1985). Codon usage and tRNA content in unicellular and multicellular organisms,
  7. (2001). Codon usage and tRNA genes in eukaryotes: correlation of codon usage diversity with translation efficiency and with CG-dinucleotide usage as assessedbymultivariateanalysis,J.Mol.Evol.,53,290–8.
  8. (2004). Control of human potassium channel inactivation by editing of a small mRNA hairpin,
  9. (2001). Controlling the false discovery rate in behavior genetics research,
  10. (1981). Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: a proposal for a synonymous codon choice that is optimal for the E. coli translational system,
  11. (1995). DNA sequence evolution: the sounds of silence,
  12. (2009). Effect of exonic splicing regulation on synonymous codon usage in alternatively spliced exons of Dscam,
  13. (2000). Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases.
  14. (2007). Exonic splicing regulatory elements skew synonymous codon usage near intron-exon boundaries in mammals,
  15. (1989). Identification of a conserved sequence in the non-coding regions of many human genes,
  16. (1996). Initial splice-site recognition and pairing during pre-mRNA splicing,
  17. (1997). Making (anti)sense of non-coding sequence conservation,
  18. (2008). Mistranslationinduced protein misfolding as a dominant constraint on coding-sequence evolution,
  19. (1987). Molecular Evolutionary Genetics.
  20. (2002). Predictive identification of exonic splicing enhancers in human genes,
  21. (1996). R: a language for data analysis and graphics,
  22. (2006). Regions of extreme synonymous codon selection in mammalian genes,
  23. (2010). RNA processing and its regulation: global insights into biological networks,
  24. (2008). Selection on codon bias,
  25. (2005). Small fitness effect of mutations in highly conserved noncoding regions,
  26. (1998). Spi-1/PU.1 proto-oncogene induces opposite effects on monocytic and erythroid differentiation of K562 cells,
  27. (1998). Synonymous and nonsynonymous substitution distances are correlated in mouse and rat genes,
  28. (1994). Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy,
  29. (1983). The Neutral Theory of Molecular Evolution.
  30. (1987). The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias,
  31. (2004). Tissuespecific codon usage and the expression of human genes,
  32. (2003). Translational selection and yeast proteome evolution,
  33. (2008). Ultraconserved coding regions outside the homeobox of mammalian Hox genes,
  34. (2004). Ultraconserved elements in the human genome,
  35. (2007). Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements,