Abundance of dinucleotide repeats and gene expression are inversely correlated: a role for gene function in addition to intron length

Abstract

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 greater or equal 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 with 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 appears 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 suggests 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 was also controlled by gene function in addition to intron length.