Assessing the conservation of mammalian gene expression using high-density exon arrays.
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: Similarity in gene expression pattern between closely linked genes is known in several eukaryotes. Two models have been proposed to explain the presence of such coexpression patterns. The adaptive model assumes that coexpression is advantageous and is established by relocation of initially unlinked but coexpressed genes, whereas the neutral model asserts that coexpression is a type of leaky expression due to similar expressional environments of linked genes, but is neither advantageous nor detrimental. However, these models are incompatible with several empirical observations. Here, we propose that coexpression of linked genes is a form of transcriptional interference that is disadvantageous to the organism. We show that even distantly linked genes that are tens of megabases away exhibit significant coexpression in the human genome. However, the linkage is more likely to be broken during evolution between genes of high coexpression than those of low coexpression and the breakage of linkage reduces gene coexpression. These results support our hypothesis that coexpression of linked genes in mammalian genomes is generally disadvantageous, implying that many mammalian genes may never reach their optimal expression pattern due to the interference of their genomic environment and that such transcriptional interference may be a force promoting recurrent relocation of genes in the genome.Molecular Biology and Evolution 09/2008; 25(8):1555-65. DOI:10.1093/molbev/msn101 · 14.31 Impact Factor
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ABSTRACT: Evolutionary developmental biology has grown historically from the capacity to relate patterns of evolution in anatomy to patterns of evolution of expression of specific genes, whether between very distantly related species, or very closely related species or populations. Scaling up such studies by taking advantage of modern transcriptomics brings promising improvements, allowing us to estimate the overall impact and molecular mechanisms of convergence, constraint or innovation in anatomy and development. But it also presents major challenges, including the computational definitions of anatomical homology and of organ function, the criteria for the comparison of developmental stages, the annotation of transcriptomics data to proper anatomical and developmental terms, and the statistical methods to compare transcriptomic data between species to highlight significant conservation or changes. In this article, we review these challenges, and the ongoing efforts to address them, which are emerging from bioinformatics work on ontologies, evolutionary statistics, and data curation, with a focus on their implementation in the context of the development of our database Bgee (http://bgee.org). J. Exp. Zool. (Mol. Dev. Evol.) 9999B: XX-XX, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.Journal of Experimental Zoology Part B Molecular and Developmental Evolution 04/2015; 324(4). DOI:10.1002/jez.b.22618 · 1.88 Impact Factor
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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 http://deepblue.lib.umich.edu/bitstream/2027.42/60816/1/liaoby_1.pdf