Analyses of Highly Conserved Nucleotide Sequences within Protein Coding Regions of Eukaryotes

鈴木, 留美子; スズキ, ルミコ; SUZUKI, Rumiko

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Analyses of Highly Conserved Nucleotide Sequences within Protein Coding Regions of Eukaryotes

https://ir.soken.ac.jp/records/2173

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Item type

学位論文 / Thesis or Dissertation(1)

公開日

2011-06-03

タイトル

Analyses of Highly Conserved Nucleotide Sequences within Protein Coding Regions of Eukaryotes

タイトル

Analyses of Highly Conserved Nucleotide Sequences within Protein Coding Regions of Eukaryotes

言語

eng

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資源タイプ識別子

http://purl.org/coar/resource_type/c_46ec

資源タイプ

thesis

著者名

鈴木, 留美子

フリガナ

スズキ, ルミコ

著者

SUZUKI, Rumiko

学位授与機関

学位授与機関名

総合研究大学院大学

学位名

博士（理学）

学位記番号

内容記述タイプ

Other

内容記述

総研大甲第1387号

研究科

値

生命科学研究科

専攻

値

18 遺伝学専攻

学位授与年月日

2010-09-30

学位授与年度

値

2010

要旨

内容記述タイプ

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内容記述

Nucleotide substitutions in the synonymous sites of codons do not alter amino acid sequences, therefore they are considered to be basically neutral. In some cases, however, synonymous sites accept selective constraints.
　　　Requirement for translational efficiency or accuracy enhances the optimum codon usage and suppress the synonymous changes. Other than this, a certain region of a protein coding gene may function as exonic splicing signals, RNA editing targets, and RNA secondary structures that affect on gene expression. There is also possibility that messenger RNAs have interaction with non-protein coding transcripts. The existence of such functional regions would be detected from suppression of nucleotide substitution in the area.
　　　Preceding studies have revealed many facts about codon biases and exonic splicing signals, however, other factors have not been extensively surveyed. The aim of this study is to explore unknown factors that affect on the nucleotide conservation in the coding regions in various taxa and to predict potential functionality of the conserved sequences.
　　　For this purpose, I investigated invariant sequences in orthologous genes in seven taxa: mammals (Homo sapiens, Macaca. mulatta, Mus musculus, Rattus norvegicus, Bos taurus, and Canis familiaris), teleosts (Tetraodon nigroviridis, Takifugu rubripes, Gasterosteus aculeatus, Oryzias latipes), Drosophilas (Drosophila melanogaster, D. simulans, D. sechellia, D. yakuba, D. erecta, D. ananassae), nematodes (Caenorhabditis elegans, C. briggsae, C. remanei, C. japonica), dicots (Arabidopsis thaliana, A. lyrata, Vitis vinifera), monocots (Oryza sativa japonica, O. s. indica, Sorghum bicolor, Brachypodium distachyon), and budding yeasts (Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. bayanus). Analysis on major codon ratio, GC content, and codon degeneracy revealed different characteristics of invariant sequences among the taxa. The major codon ratio decreases as the conservation length elongates in the four animal taxa (mammals, teleosts, Drosophilas, and nematodes), while GC content and codon degeneracy do not show notable sway. This result implies that selection toward optimum codons may not be the dominant factor in the above taxa.
　　　To extract sequences whose conservation is stronger than others, I took a permutation approach. I permuted codons of each alignment and surveyed the length and frequency of invariant sequences in the permuted alignment. In the mammals, the result of permutation showed significant deviation from the number of invariant sequences in the original alignments (p < 2.2E-16) but deviation is subtle in budding yeasts. This result implies that the distribution of conserved sites is skewed in mammals, while the distribution is rather homogeneous in the budding yeasts. I extracted from the original alignments invariant sequences that have significantly low expectancy (P < 0.01) in comparison with the permutation results and defined them as significantly conserved coding sequences (SCCSs).
　　　These analyses revealed different characteristics of conserved nucleotide sequences among the taxa. In mammals and teleosts, it’s not likely that long SCCSs has been retained solely by amino acid constraint judging from the codon degeneracy and negative correlation between the conservation length and major codon ratio. The sequence characteristics and skewed distribution of conserved sites predicted from the permutation result suggest that SCCSs of the above tow taxa have rather preferable traits as functional nucleotide elements.
　　　SCCSs are extracted from the alignments of orthologs in one taxon, but there are SCCSs that are observed in the similar regions of orthologs in multiple taxa. Although the sequence similarity varies case by case, it is notable that SCCSs are alignable between the distant taxa. This may happen if strong amino acid constraint is working on the similar regions of the genes. However, such constraint does not fully explain the SCCSs that exist out of protein domains, where amino acid constraint is not necessarily strong, and how synonymous sites in codons of moderate degeneracy are retained for a long period.
　　　There are cases that specific RNA secondary structures exert some functions. I computationally predicted RNA secondary structures of SCCS regions using Vienna RNA package and detected five SCCSs that form secondary structures of significantly low folding free energy (P < 0.05). The corresponding regions of platypus and opossum orthologs showed sequence similarity but the structures are more stable in the placental mammals. Although the roles of these structures are unknown, strong conservation and significantly low free energy suggest the possibility that these regions have some functions.
　　　As for mammals, I investigated exonic splicing signals and non-protein coding RNAs that overlaps with SCCSs or non-SCCS coding regions. No significant difference is observed in splicing signal density between SCCSs and non-SCCS coding regions, however, the component of non-protein coding RNAs overlapped with SCCSs show difference from those overlapped with non-SCCS regions. This result suggests that non-protein coding RNAs may have some association with SCCSs in mammals.

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Analyses of Highly Conserved Nucleotide Sequences within Protein Coding Regions of Eukaryotes

× 鈴木, 留美子

× スズキ, ルミコ

× SUZUKI, Rumiko

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