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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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Correlations between the level of human-mouse evolutionarily divergence in protein coding regions and 3′UTRs of ubiquitous and differentially expressed human PK genes.A. Correlations between evolutionarily divergence in protein coding regions and 3′UTRs of high, low, and ubiquitously expression PK genes. B. Correlations between evolutionarily divergence in protein coding regions and 3′UTRs of PK genes up-regulated and down-regulated in nervous and testicular tissues.
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pone-0003599-g004: Correlations between the level of human-mouse evolutionarily divergence in protein coding regions and 3′UTRs of ubiquitous and differentially expressed human PK genes.A. Correlations between evolutionarily divergence in protein coding regions and 3′UTRs of high, low, and ubiquitously expression PK genes. B. Correlations between evolutionarily divergence in protein coding regions and 3′UTRs of PK genes up-regulated and down-regulated in nervous and testicular tissues.

Mentions: We compared evolutionary rates in transcribed domains of PK and non-PK genes by evaluating the human-mouse evolutionary divergence in 5′UTRs (K5′), CDSs (Ke), introns (Ki), and 3′UTRs (K3′) using Kimura's two parameter model [28]. PK genes are characterized with lower Ke values, relative to non-PK genes, reflecting higher constraint on amino acid sequences. We also observed increased Ki values in PK introns, as compared to non-PK introns. As shown in Table 2, evolutionary divergence was significantly lower for both PK and non-PK genes in 5′UTRs (p<10−7) and 3′UTRs (p<10−5), relative to introns. We found significant positive correlations between levels of evolutionary divergence in CDSs and 3′UTR, in CDSs and 5′UTRs of PK genes (Figure 3B). Similar to Ka values, K3′ values inversely correlated with breadth of gene expression (R = −0.11, p<0.01). Positive correlation between Ke and K3′ values was observed for PKs predominantly expressed in nervous tissue, and for other differentially expressed PK groups (Figure 4). This trend was also observed for slow evolving ubiquitous PKs.


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)

Correlations between the level of human-mouse evolutionarily divergence in protein coding regions and 3′UTRs of ubiquitous and differentially expressed human PK genes.A. Correlations between evolutionarily divergence in protein coding regions and 3′UTRs of high, low, and ubiquitously expression PK genes. B. Correlations between evolutionarily divergence in protein coding regions and 3′UTRs of PK genes up-regulated and down-regulated in nervous and testicular tissues.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003599-g004: Correlations between the level of human-mouse evolutionarily divergence in protein coding regions and 3′UTRs of ubiquitous and differentially expressed human PK genes.A. Correlations between evolutionarily divergence in protein coding regions and 3′UTRs of high, low, and ubiquitously expression PK genes. B. Correlations between evolutionarily divergence in protein coding regions and 3′UTRs of PK genes up-regulated and down-regulated in nervous and testicular tissues.
Mentions: We compared evolutionary rates in transcribed domains of PK and non-PK genes by evaluating the human-mouse evolutionary divergence in 5′UTRs (K5′), CDSs (Ke), introns (Ki), and 3′UTRs (K3′) using Kimura's two parameter model [28]. PK genes are characterized with lower Ke values, relative to non-PK genes, reflecting higher constraint on amino acid sequences. We also observed increased Ki values in PK introns, as compared to non-PK introns. As shown in Table 2, evolutionary divergence was significantly lower for both PK and non-PK genes in 5′UTRs (p<10−7) and 3′UTRs (p<10−5), relative to introns. We found significant positive correlations between levels of evolutionary divergence in CDSs and 3′UTR, in CDSs and 5′UTRs of PK genes (Figure 3B). Similar to Ka values, K3′ values inversely correlated with breadth of gene expression (R = −0.11, p<0.01). Positive correlation between Ke and K3′ values was observed for PKs predominantly expressed in nervous tissue, and for other differentially expressed PK groups (Figure 4). This trend was also observed for slow evolving ubiquitous PKs.

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