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Genetics, Vol. 167, 1293-1304, July 2004, Copyright © 2004
doi:10.1534/genetics.104.026351
Selective and Mutational Patterns Associated With Gene Expression in Humans
Influences on Synonymous Composition and Intron Presence
Josep M. Comeron1
Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242
1 Address for correspondence: Department of Biological Sciences, University of Iowa, 212 Biology Bldg. (BB), Iowa City, IA 52242.
E-mail: josep-comeron{at}uiowa.edu
We report the results of a comprehensive study of the influence of gene expression on synonymous codons, amino acid composition, and intron presence and size in human protein-coding genes. First, in addition to a strong effect of isochores, we have detected the influence of transcription-associated mutational biases (TAMB) on gene composition. Genes expressed in different tissues show diverse degrees of TAMB, with genes expressed in testis showing the greatest influence. Second, the study of tissues with no evidence of TAMB reveals a consistent set of optimal synonymous codons favored in highly expressed genes. This result exposes the consequences of natural selection on synonymous composition to increase efficiency of translation in the human lineage. Third, overall amino acid composition of proteins closely resembles tRNA abundance but there is no difference in amino acid composition in differentially expressed genes. Fourth, there is a negative relationship between expression and CDS length. Significantly, this is observed only among genes with introns, suggesting that the cause for this relationship in humans cannot be associated only with costs of amino acid biosynthesis. Fifth, we show that broadly and highly expressed genes have more, although shorter, introns. The selective advantage for having more introns in highly expressed genes is likely counterbalanced by containment of transcriptional costs and a minimum exon size for proper splicing.
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