Assessing the conservation of mammalian gene expression using high-density exon arrays.

Molecular Biology and Evolution (Impact Factor: 14.31). 07/2007; 24(6):1283-5. DOI: 10.1093/molbev/msm061
Source: PubMed

ABSTRACT Microarray data from multiple species have been used to study evolutionary constraints on gene expression. Expression measurements from conventional microarray platforms such as the 3' expression arrays are strongly affected by platform-dependent probe effects that may introduce apparent but misleading discrepancies between species. In this manuscript, we assess the conservation of mammalian gene expression in adult tissues using data from a high-density exon array platform. The exon arrays have more than 6 million probes on a single array targeting all exons in a genome. We find that, unlike 3' array data, gene expression measurements from exon arrays reveal patterns of gene expression that are highly conserved between humans and mice in multiple tissues. Our analysis provides strong evidence for widespread stabilizing selection pressure on transcript abundance during mammalian evolution.

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    ABSTRACT: Comparing the expression-profiles of over 10,000 genes from the human and mouse genomes, I address fundamental questions on mammalian gene expression. First, I demonstrate that over 80% of human-mouse orthologous genes are evolutionarily conserved in their expression-profiles. This result highlights the importance of proper gene expression to fitness. Second, I show that highly expressed and tissue-specific genes tend to evolve slowly in expression-profile, implying that the expression pattern is of particular importance to highly expressed and tissue-specific genes. I then investigate the potential roles that gene expression plays in protein sequence evolution, dynamics of genome organization, and evolutionary changes of gene essentiality in mammals. My results indicate that tissue-specificity is a stronger determinant on protein evolutionary rate than gene expression level, a factor that is known to be the most important rate determinant in yeasts. The result suggests a great variation in rate determinants of protein sequence evolution between unicellular and multicellular organisms. Subsequently, my analyses on the origin of co-expressed gene clusters indicate that co-expression of linked genes is a form of transcriptional interference that is disadvantageous to organisms, suggesting that transcriptional interference may promote recurrent relocations of genes in the genome. Lastly, I study underlying mechanisms of the evolution of gene essentiality. The results show that the changes of gene essentiality appear to be associated with adaptive evolution at the protein-sequence level, while gene duplication and gene expression evolution plays a negligible role. Together, my studies help understand patterns, mechanisms and consequences of gene expression evolution. Ph.D. Ecology and Evolutionary Biology University of Michigan, Horace H. Rackham School of Graduate Studies