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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

The length of the structural domains in human PK and non-PK genes.The following groups of differentially expressed PK genes were analyzed: all PK genes, high expression genes (75 genes with highest EST numbers), low expression genes (75 genes with lowest EST numbers), ubiquitously expressed genes, genes up-regulated in the nervous or testicular tissue, genes down-regulated in the nervous or testicular tissue. Sequence conservation was evaluated relative to mouse gene orthologs. CDS of extremely large PK titin was excluded from this analysis. Data are presented as averages.
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pone-0003599-g002: The length of the structural domains in human PK and non-PK genes.The following groups of differentially expressed PK genes were analyzed: all PK genes, high expression genes (75 genes with highest EST numbers), low expression genes (75 genes with lowest EST numbers), ubiquitously expressed genes, genes up-regulated in the nervous or testicular tissue, genes down-regulated in the nervous or testicular tissue. Sequence conservation was evaluated relative to mouse gene orthologs. CDS of extremely large PK titin was excluded from this analysis. Data are presented as averages.

Mentions: For evaluation of gene architecture, we analyzed length and GC content in different gene functional domains in 510 human PK genomic loci. To compare structural properties of PK genes with overall trends for other genes, we used control group of 7,711 well-annotated human non-PK genes. Genomic architecture of PK and non-PK genes significantly differed. As seen from Figure 2, PK genes occupy larger genomic loci, possess significantly longer exons and spacer regions, and encode larger proteins, relative to the group of non-PK genes. PK genes also tend to have more GC-rich UTRs relative to non-PK genes (Table 1). Remarkably, lengths of gene loci, 5′-spacers, introns and UTRs of the human PK genes were ∼15% longer than for the mouse PK genes, revealing higher gene complexity (Figure S1). Same trend was observed for non-PK genes (data not shown).


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)

The length of the structural domains in human PK and non-PK genes.The following groups of differentially expressed PK genes were analyzed: all PK genes, high expression genes (75 genes with highest EST numbers), low expression genes (75 genes with lowest EST numbers), ubiquitously expressed genes, genes up-regulated in the nervous or testicular tissue, genes down-regulated in the nervous or testicular tissue. Sequence conservation was evaluated relative to mouse gene orthologs. CDS of extremely large PK titin was excluded from this analysis. Data are presented as averages.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003599-g002: The length of the structural domains in human PK and non-PK genes.The following groups of differentially expressed PK genes were analyzed: all PK genes, high expression genes (75 genes with highest EST numbers), low expression genes (75 genes with lowest EST numbers), ubiquitously expressed genes, genes up-regulated in the nervous or testicular tissue, genes down-regulated in the nervous or testicular tissue. Sequence conservation was evaluated relative to mouse gene orthologs. CDS of extremely large PK titin was excluded from this analysis. Data are presented as averages.
Mentions: For evaluation of gene architecture, we analyzed length and GC content in different gene functional domains in 510 human PK genomic loci. To compare structural properties of PK genes with overall trends for other genes, we used control group of 7,711 well-annotated human non-PK genes. Genomic architecture of PK and non-PK genes significantly differed. As seen from Figure 2, PK genes occupy larger genomic loci, possess significantly longer exons and spacer regions, and encode larger proteins, relative to the group of non-PK genes. PK genes also tend to have more GC-rich UTRs relative to non-PK genes (Table 1). Remarkably, lengths of gene loci, 5′-spacers, introns and UTRs of the human PK genes were ∼15% longer than for the mouse PK genes, revealing higher gene complexity (Figure S1). Same trend was observed for non-PK genes (data not shown).

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