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Expression patterns of protein kinases correlate with gene architecture and evolutionary rates.

Ogurtsov AY, Mariño-Ramírez L, Johnson GR, Landsman D, Shabalina SA, Spiridonov NA - PLoS ONE (2008)

Bottom Line: The primary transcript length of PK genes, similar to other protein coding genes, inversely correlates with gene expression level and expression breadth, which is likely due to the necessity to reduce metabolic costs of transcription for abundant messages.Structure and evolutionary divergence of tissue-specific PK genes is related to the proliferative activity of the tissue where these genes are predominantly expressed.Our data provide evidence that physiological requirements for transcription intensity, ubiquitous expression, and tissue-specific regulation shape gene structure and affect rates of evolution.

View Article: PubMed Central - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.

ABSTRACT

Background: Protein kinase (PK) genes comprise the third largest superfamily that occupy approximately 2% of the human genome. They encode regulatory enzymes that control a vast variety of cellular processes through phosphorylation of their protein substrates. Expression of PK genes is subject to complex transcriptional regulation which is not fully understood.

Principal findings: Our comparative analysis demonstrates that genomic organization of regulatory PK genes differs from organization of other protein coding genes. PK genes occupy larger genomic loci, have longer introns, spacer regions, and encode larger proteins. The primary transcript length of PK genes, similar to other protein coding genes, inversely correlates with gene expression level and expression breadth, which is likely due to the necessity to reduce metabolic costs of transcription for abundant messages. On average, PK genes evolve slower than other protein coding genes. Breadth of PK expression negatively correlates with rate of non-synonymous substitutions in protein coding regions. This rate is lower for high expression and ubiquitous PKs, relative to low expression PKs, and correlates with divergence in untranslated regions. Conversely, rate of silent mutations is uniform in different PK groups, indicating that differing rates of non-synonymous substitutions reflect variations in selective pressure. Brain and testis employ a considerable number of tissue-specific PKs, indicating high complexity of phosphorylation-dependent regulatory network in these organs. There are considerable differences in genomic organization between PKs up-regulated in the testis and brain. PK genes up-regulated in the highly proliferative testicular tissue are fast evolving and small, with short introns and transcribed regions. In contrast, genes up-regulated in the minimally proliferative nervous tissue carry long introns, extended transcribed regions, and evolve slowly.

Conclusions/significance: PK genomic architecture, the size of gene functional domains and evolutionary rates correlate with the pattern of gene expression. Structure and evolutionary divergence of tissue-specific PK genes is related to the proliferative activity of the tissue where these genes are predominantly expressed. Our data provide evidence that physiological requirements for transcription intensity, ubiquitous expression, and tissue-specific regulation shape gene structure and affect rates of evolution.

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Related in: MedlinePlus

Relative tissue distribution and abundance of EST for 7,711 non-PK genes and 512 PK genes in GenBank, release 162.A. Relative tissue distribution of gene-specific EST for non-PK and PK genes. B. Abundance of PK-specific ESTs in libraries from normal human tissues. The data were graphed as EST number versus PK rank.
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pone-0003599-g001: Relative tissue distribution and abundance of EST for 7,711 non-PK genes and 512 PK genes in GenBank, release 162.A. Relative tissue distribution of gene-specific EST for non-PK and PK genes. B. Abundance of PK-specific ESTs in libraries from normal human tissues. The data were graphed as EST number versus PK rank.

Mentions: We evaluated expression of PK and non-PK genes based on the numbers of gene-specific ESTs in GenBank originating from normal human tissues, which reflect mRNA abundance and relative gene transcription levels. The vast majority of PK genes scored moderate EST numbers (84 ESTs average) in contrast with highly transcribed housekeeping non-PK genes (2000 or more ESTs). Based on this analysis, PKs fall into a category of moderately transcribed genes, which is consistent with their regulatory role. These data are in agreement with overall PK expression levels presented in the Gene Expression Atlas. For evaluation of PK expression patterns and the relative abundance of PK messages in different organs, we sorted gene-specific ESTs in accordance with their organ and tissue origins. ESTs originating from the brain and nervous tissue were most numerous in our dataset, followed by ESTs from testis and placenta (Figure 1). Distribution of PK-specific ESTs in 20 normal human organs and tissues is presented in Table S1. Our results showed that the majority of PK genes were broadly expressed in many tissues. At the same time, a number of PK genes showed distinct organ-specific and tissue-specific expression patterns.


Expression patterns of protein kinases correlate with gene architecture and evolutionary rates.

Ogurtsov AY, Mariño-Ramírez L, Johnson GR, Landsman D, Shabalina SA, Spiridonov NA - PLoS ONE (2008)

Relative tissue distribution and abundance of EST for 7,711 non-PK genes and 512 PK genes in GenBank, release 162.A. Relative tissue distribution of gene-specific EST for non-PK and PK genes. B. Abundance of PK-specific ESTs in libraries from normal human tissues. The data were graphed as EST number versus PK rank.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2572838&req=5

pone-0003599-g001: Relative tissue distribution and abundance of EST for 7,711 non-PK genes and 512 PK genes in GenBank, release 162.A. Relative tissue distribution of gene-specific EST for non-PK and PK genes. B. Abundance of PK-specific ESTs in libraries from normal human tissues. The data were graphed as EST number versus PK rank.
Mentions: We evaluated expression of PK and non-PK genes based on the numbers of gene-specific ESTs in GenBank originating from normal human tissues, which reflect mRNA abundance and relative gene transcription levels. The vast majority of PK genes scored moderate EST numbers (84 ESTs average) in contrast with highly transcribed housekeeping non-PK genes (2000 or more ESTs). Based on this analysis, PKs fall into a category of moderately transcribed genes, which is consistent with their regulatory role. These data are in agreement with overall PK expression levels presented in the Gene Expression Atlas. For evaluation of PK expression patterns and the relative abundance of PK messages in different organs, we sorted gene-specific ESTs in accordance with their organ and tissue origins. ESTs originating from the brain and nervous tissue were most numerous in our dataset, followed by ESTs from testis and placenta (Figure 1). Distribution of PK-specific ESTs in 20 normal human organs and tissues is presented in Table S1. Our results showed that the majority of PK genes were broadly expressed in many tissues. At the same time, a number of PK genes showed distinct organ-specific and tissue-specific expression patterns.

Bottom Line: The primary transcript length of PK genes, similar to other protein coding genes, inversely correlates with gene expression level and expression breadth, which is likely due to the necessity to reduce metabolic costs of transcription for abundant messages.Structure and evolutionary divergence of tissue-specific PK genes is related to the proliferative activity of the tissue where these genes are predominantly expressed.Our data provide evidence that physiological requirements for transcription intensity, ubiquitous expression, and tissue-specific regulation shape gene structure and affect rates of evolution.

View Article: PubMed Central - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.

ABSTRACT

Background: Protein kinase (PK) genes comprise the third largest superfamily that occupy approximately 2% of the human genome. They encode regulatory enzymes that control a vast variety of cellular processes through phosphorylation of their protein substrates. Expression of PK genes is subject to complex transcriptional regulation which is not fully understood.

Principal findings: Our comparative analysis demonstrates that genomic organization of regulatory PK genes differs from organization of other protein coding genes. PK genes occupy larger genomic loci, have longer introns, spacer regions, and encode larger proteins. The primary transcript length of PK genes, similar to other protein coding genes, inversely correlates with gene expression level and expression breadth, which is likely due to the necessity to reduce metabolic costs of transcription for abundant messages. On average, PK genes evolve slower than other protein coding genes. Breadth of PK expression negatively correlates with rate of non-synonymous substitutions in protein coding regions. This rate is lower for high expression and ubiquitous PKs, relative to low expression PKs, and correlates with divergence in untranslated regions. Conversely, rate of silent mutations is uniform in different PK groups, indicating that differing rates of non-synonymous substitutions reflect variations in selective pressure. Brain and testis employ a considerable number of tissue-specific PKs, indicating high complexity of phosphorylation-dependent regulatory network in these organs. There are considerable differences in genomic organization between PKs up-regulated in the testis and brain. PK genes up-regulated in the highly proliferative testicular tissue are fast evolving and small, with short introns and transcribed regions. In contrast, genes up-regulated in the minimally proliferative nervous tissue carry long introns, extended transcribed regions, and evolve slowly.

Conclusions/significance: PK genomic architecture, the size of gene functional domains and evolutionary rates correlate with the pattern of gene expression. Structure and evolutionary divergence of tissue-specific PK genes is related to the proliferative activity of the tissue where these genes are predominantly expressed. Our data provide evidence that physiological requirements for transcription intensity, ubiquitous expression, and tissue-specific regulation shape gene structure and affect rates of evolution.

Show MeSH
Related in: MedlinePlus