The Human Transcriptome Map Reveals Extremes in Gene Density, Intron Length, GC Content, and Repeat Pattern for Domains of Highly and Weakly Expressed Genes

Abstract

The chromosomal gene expression profiles established by the Human Transcriptome Map (HTM) revealed a clustering of highly expressed genes in about 30 domains, called ridges. To physically characterize ridges, we constructed a new HTM based on the draft human genome sequence (HTMseq). Expression of 25,003 genes can be analyzed online in a multitude of tissues (http://bioinfo.amc.uva.nl/HTMseq). Ridges are found to be very gene-dense domains with a high GC content, a high SINE repeat density, and a low LINE repeat density. Genes in ridges have significantly shorter introns than genes outside of ridges. The HTMseq also identifies a significant clustering of weakly expressed genes in domains with fully opposite characteristics (antiridges). Both types of domains are open to tissue-specific expression regulation, but the maximal expression levels in ridges are considerably higher than in antiridges. Ridges are therefore an integral part of a higher order structure in the genome related to transcriptional regulation.

Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

“…10e). Intron length in the chicken correlates negatively with recombination (r s ¼ 2 0.774, P , 0.001), G+C content (r s ¼ 2 0.934, P , 0.001) and gene density (r s ¼ 2 0.961, P , 0.001), as has been reported previously for other genomes [120][121][122][123] . The proportion of a chromosome covered by interspersed repeats increases with chromosome length (Fig.…”

Is optimal gene order impossible?

“…This idea is supported by the finding that genes that are similarly expressed are found in clusters (e.g. genes that are co-expressed [5][6][7] and/or broadly expressed [8,9] and/or highly expressed [10,11]). Second, genome proximity might evolve to reduce the recombination rate between specific genes [12,13].…”

Genomic Regionality in Rates of Evolution Is Not Explained by Clustering of Genes of Comparable Expression Profile

“…In particular, we examine the hypothesis that transcriptional activity provides a possible mechanistic basis for both clustering phenomena (Hurst and Eyre-Walker 2000;Williams and Hurst 2002;Hardison et al 2003). A priori, a coupling with transcriptional activity is an attractive hypothesis, as genes with comparable expression profile cluster (Caron et al 2001;Lercher et al 2003;Versteeg et al 2003) and expression parameters are related to substitution rates (Duret and Mouchiroud 2000). We show here that transcriptional activity appears not to be an important variable underpinning local similarity of rates of evolution.…”

“…Prior evidence suggests the possibility of a weak reduction in the synonymous rate of substitution in putatively germline-expressed genes (Duret and Mouchiroud 2000). Given too that it has been shown that highly expressed genes are clustered in the human genome (Caron et al 2001;Versteeg et al 2003), transcriptionally mediated variations in the mutation rate could potentially lead to the observation of local similarity.…”