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Physiol. Genomics (June 5, 2007). doi:10.1152/physiolgenomics.00183.2006
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Submitted on August 22, 2006
Accepted on May 30, 2007

Abundance of Dinucleotide Repeats and Gene Expression are Inversely Correlated: a role for gene function in addition to intron length

Vineet K. Sharma1, Naveen Kumar1, Samir K. Brahmachari1, and Srinivasan Ramachandran1*

1 G.N. Ramachandran Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, Delhi, India

* To whom correspondence should be addressed. E-mail: ramuigib{at}gmail.com.

High and broad transcription of eukaryotic genes is facilitated by cost minimization, clustered localization in the genome, elevated G+C content and low nucleosome formation potential. In this scenario, illumination of correlation between abundance of (TG/CA)n≥12 repeats, which are negative cis modulators of transcription and transcriptional levels and other commonly occurring dinucleotide repeats is required. Three independent microarray datasets were used to examine the correlation of (TG/CA)n≥12 and other dinucleotide repeats with gene expression. Compared to the expected equi-distribution pattern under neutral model, highly transcribed genes were poor in repeats and conversely, weakly transcribed genes were rich in repeats. Furthermore, the inverse correlation between repeat abundance and transcriptional levels appear to be a global phenomenon encompassing all genes regardless of their breadth of transcription. This selective pattern of exclusion of (TG/CA)n≥12 and (AT)n≥12 repeats in highly transcribed genes is an additional factor along with cost minimization and elevated GC and therefore, multiple factors govern high transcription of genes. We observed that even after controlling for the effects of GC and average intron lengths, the effect of repeats albeit somewhat weaker was persistent and definite. In the ribosomal protein coding genes, sequence analysis of orthologs suggest that negative selection for repeats perhaps occurred early in evolution. These observations suggest that negative selection of (TG/CA)n≥12 microsatellites in the evolution of the highly expressed genes were also controlled by gene function in addition to intron length.




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