Expression Evolution of Mammalian Genes.

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.