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• W1976809311 endingPage "e3599" @default.
• W1976809311 startingPage "e3599" @default.
• W1976809311 abstract "Background Protein kinase (PK) genes comprise the third largest superfamily that occupy ∼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." @default.
• W1976809311 created "2016-06-24" @default.
• W1976809311 creator A5001484555 @default.
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• W1976809311 creator A5077908609 @default.
• W1976809311 creator A5079340857 @default.
• W1976809311 date "2008-10-31" @default.
• W1976809311 modified "2023-09-25" @default.
• W1976809311 title "Expression Patterns of Protein Kinases Correlate with Gene Architecture and Evolutionary Rates" @default.
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• W1976809311 doi "https://doi.org/10.1371/journal.pone.0003599" @default.
• W1976809311 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2572838" @default.
• W1976809311 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18974838" @default.
• W1976809311 hasPublicationYear "2008" @default.
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