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Weak correlation between sequence conservation in promoter regions and in protein-coding regions of human-mouse orthologous gene pairs.

Chiba H, Yamashita R, Kinoshita K, Nakai K - BMC Genomics (2008)

Bottom Line: A number of studies have compared protein sequences or promoter sequences between mammals, which provided many insights into genomics.Remarkably, the 'ribosome' category showed significantly low promoter conservation, despite its high protein conservation, and the 'extracellular matrix' category showed significantly high promoter conservation, in spite of its low protein conservation.Our results show the relation of gene function to protein conservation and promoter conservation, and revealed that there seem to be nonparallel components between protein and promoter sequence evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. hchiba@hgc.jp <hchiba@hgc.jp>

ABSTRACT

Background: Interspecies sequence comparison is a powerful tool to extract functional or evolutionary information from the genomes of organisms. A number of studies have compared protein sequences or promoter sequences between mammals, which provided many insights into genomics. However, the correlation between protein conservation and promoter conservation remains controversial.

Results: We examined promoter conservation as well as protein conservation for 6,901 human and mouse orthologous genes, and observed a very weak correlation between them. We further investigated their relationship by decomposing it based on functional categories, and identified categories with significant tendencies. Remarkably, the 'ribosome' category showed significantly low promoter conservation, despite its high protein conservation, and the 'extracellular matrix' category showed significantly high promoter conservation, in spite of its low protein conservation.

Conclusion: Our results show the relation of gene function to protein conservation and promoter conservation, and revealed that there seem to be nonparallel components between protein and promoter sequence evolution.

Show MeSH
Distribution of alignment scores of human and mouse promoters for several categories with significant tendencies. For the high conservation tendency, actin cytoskeleton (A) and extracellular matrix (B), for the low conservation tendency, lysosome (C) and ribosome (D). For each of A-D, the solid line shows the distribution of the alignment scores for genes with the specific GO term, and the dashed line shows the distribution for the control gene set (see Materials and Methods for details).
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Figure 2: Distribution of alignment scores of human and mouse promoters for several categories with significant tendencies. For the high conservation tendency, actin cytoskeleton (A) and extracellular matrix (B), for the low conservation tendency, lysosome (C) and ribosome (D). For each of A-D, the solid line shows the distribution of the alignment scores for genes with the specific GO term, and the dashed line shows the distribution for the control gene set (see Materials and Methods for details).

Mentions: Based on the promoter sequence comparison between human and mouse for the 6,901 genes, we investigated the relationship between gene function and promoter conservation. Annotations of genes were made by associating human genes with GO terms. To this end, we developed a slimmed-down version of the GO vocabulary, containing 52 terms for biological process (P), 22 for cellular component (C) and 26 for molecular function (F) (see Materials and Methods and Additional file 2 for details). We tested whether the alignment scores for a set of genes associated with a GO term are significantly high or low by a Wilcoxon rank sum test. The resulting GO terms with high promoter conservation are listed in Table 1, and those with low conservation are in Table 2 (only terms with a P-value < 0.01 are in the tables; for the complete list of results, see Additional file 3). Figure 2 shows the distributions of the alignment scores for several GO terms with significant tendencies (all of the distributions for the GO terms listed in Table 1 and 2 are shown in Additional file 4). When we tried the global alignment score, we obtained quite similar tendencies (data not shown). We also confirmed that eliminating the coding sequences from the promoter dataset does not significantly influence the observed tendencies (data not shown, see Materials and Methods for details).


Weak correlation between sequence conservation in promoter regions and in protein-coding regions of human-mouse orthologous gene pairs.

Chiba H, Yamashita R, Kinoshita K, Nakai K - BMC Genomics (2008)

Distribution of alignment scores of human and mouse promoters for several categories with significant tendencies. For the high conservation tendency, actin cytoskeleton (A) and extracellular matrix (B), for the low conservation tendency, lysosome (C) and ribosome (D). For each of A-D, the solid line shows the distribution of the alignment scores for genes with the specific GO term, and the dashed line shows the distribution for the control gene set (see Materials and Methods for details).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2335122&req=5

Figure 2: Distribution of alignment scores of human and mouse promoters for several categories with significant tendencies. For the high conservation tendency, actin cytoskeleton (A) and extracellular matrix (B), for the low conservation tendency, lysosome (C) and ribosome (D). For each of A-D, the solid line shows the distribution of the alignment scores for genes with the specific GO term, and the dashed line shows the distribution for the control gene set (see Materials and Methods for details).
Mentions: Based on the promoter sequence comparison between human and mouse for the 6,901 genes, we investigated the relationship between gene function and promoter conservation. Annotations of genes were made by associating human genes with GO terms. To this end, we developed a slimmed-down version of the GO vocabulary, containing 52 terms for biological process (P), 22 for cellular component (C) and 26 for molecular function (F) (see Materials and Methods and Additional file 2 for details). We tested whether the alignment scores for a set of genes associated with a GO term are significantly high or low by a Wilcoxon rank sum test. The resulting GO terms with high promoter conservation are listed in Table 1, and those with low conservation are in Table 2 (only terms with a P-value < 0.01 are in the tables; for the complete list of results, see Additional file 3). Figure 2 shows the distributions of the alignment scores for several GO terms with significant tendencies (all of the distributions for the GO terms listed in Table 1 and 2 are shown in Additional file 4). When we tried the global alignment score, we obtained quite similar tendencies (data not shown). We also confirmed that eliminating the coding sequences from the promoter dataset does not significantly influence the observed tendencies (data not shown, see Materials and Methods for details).

Bottom Line: A number of studies have compared protein sequences or promoter sequences between mammals, which provided many insights into genomics.Remarkably, the 'ribosome' category showed significantly low promoter conservation, despite its high protein conservation, and the 'extracellular matrix' category showed significantly high promoter conservation, in spite of its low protein conservation.Our results show the relation of gene function to protein conservation and promoter conservation, and revealed that there seem to be nonparallel components between protein and promoter sequence evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. hchiba@hgc.jp <hchiba@hgc.jp>

ABSTRACT

Background: Interspecies sequence comparison is a powerful tool to extract functional or evolutionary information from the genomes of organisms. A number of studies have compared protein sequences or promoter sequences between mammals, which provided many insights into genomics. However, the correlation between protein conservation and promoter conservation remains controversial.

Results: We examined promoter conservation as well as protein conservation for 6,901 human and mouse orthologous genes, and observed a very weak correlation between them. We further investigated their relationship by decomposing it based on functional categories, and identified categories with significant tendencies. Remarkably, the 'ribosome' category showed significantly low promoter conservation, despite its high protein conservation, and the 'extracellular matrix' category showed significantly high promoter conservation, in spite of its low protein conservation.

Conclusion: Our results show the relation of gene function to protein conservation and promoter conservation, and revealed that there seem to be nonparallel components between protein and promoter sequence evolution.

Show MeSH