Article

Conservation of core gene expression in vertebrate tissues

Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario, Canada.
Journal of Biology 05/2009; 8(3):33. DOI: 10.1186/jbiol130
Source: PubMed

ABSTRACT Vertebrates share the same general body plan and organs, possess related sets of genes, and rely on similar physiological mechanisms, yet show great diversity in morphology, habitat and behavior. Alteration of gene regulation is thought to be a major mechanism in phenotypic variation and evolution, but relatively little is known about the broad patterns of conservation in gene expression in non-mammalian vertebrates.
We measured expression of all known and predicted genes across twenty tissues in chicken, frog and pufferfish. By combining the results with human and mouse data and considering only ten common tissues, we have found evidence of conserved expression for more than a third of unique orthologous genes. We find that, on average, transcription factor gene expression is neither more nor less conserved than that of other genes. Strikingly, conservation of expression correlates poorly with the amount of conserved nonexonic sequence, even using a sequence alignment technique that accounts for non-collinearity in conserved elements. Many genes show conserved human/fish expression despite having almost no nonexonic conserved primary sequence.
There are clearly strong evolutionary constraints on tissue-specific gene expression. A major challenge will be to understand the precise mechanisms by which many gene expression patterns remain similar despite extensive cis-regulatory restructuring.

Download full-text

Full-text

Available from: Andrew Wilde, Aug 22, 2015
0 Followers
 · 
190 Views
  • Source
    • "We used high-throughput Illumina sequencing (RNA-seq) to identify transcribed genes in the endometrium during pregnancy in five Eutherian mammals (dog, cow, horse, pig, and armadillo), a marsupial (short-tailed opossum), and a Monotreme (platypus) and combined these data with existing gene expression data from the decidualized Rhesus monkey endometrium (Liu et al., 2012), decidualized mouse endometrium (McConaha et al., 2011), pregnant lizard uterus (Brandley et al., 2012), chicken uterus (Chan et al., 2010), and frog uterus (Chan et al., 2009). We also used RNA-seq to identify transcribed genes in human decidualized endometrial stromal cells (DSCs) in culture and combined these data with existing gene expression data from human decidual natural killer (dNK) cells (Hanna et al., 2006), decidual macrophage cells (dMP) (Svensson et al., 2011), and decidual endothelial cells (dECs). "
    [Show abstract] [Hide abstract]
    ABSTRACT: A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs). Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 01/2015; 10(4). DOI:10.1016/j.celrep.2014.12.052 · 8.36 Impact Factor
  • Source
    • "The difference in tumor outcome in the intestine of rats and mice may arise from overall differences in dosimetry (pharmacokinetics) rather than pharmacodynamics (Proctor et al., in press). While gene expression patterns appear to be similar across species at the tissue level, the basal gene expression patterns across tissues appear to be different – even within the same species (Chan et al., 2009; Jonker et al., 2009; Zheng-Bradley et al., 2010). Thus, a third uncertainty in the analyses herein is whether differential gene responses in the liver should be compared to differential gene responses in the duodenum. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In vitro studies on hexavalent chromium [Cr(VI)] indicate that reduced forms of this metal can interact with DNA and cause mutations. Recently, Cr(VI) was shown to induce intestinal tumors in mice; however, Cr(VI) elicited redox changes, cytotoxicity and hyperplasia - suggesting involvement of tissue injury rather than direct mutagenesis. Moreover, toxicogenomic analyses indicated limited evidence for DNA damage responses. Herein, we extend these toxicogenomic analyses by comparing the gene expression patterns elicited by Cr(VI) with those of four mutagenic and four nonmutagenic carcinogens. To date, toxicogenomic profiles for mutagenic and nonmutagenic duodenal carcinogens do not exist, thus duodenal gene changes in mice were compared to those elicited by hepatocarcinogens. Specifically, duodenal gene changes in mice following exposure to Cr(VI) in drinking water were compared to hepatic gene changes previously identified as potentially discriminating mutagenic and nonmutagenic hepatocarcinogens. Using multivariate statistical analyses (including logistic regression classification), the Cr(VI) gene responses clustered apart from mutagenic carcinogens and closely with nonmutagenic carcinogens. These findings are consistent with other intestinal data supporting a nonmutagenic mode of action (MOA). These findings may be useful as part of a full weight of evidence MOA evaluation for Cr(VI)-induced intestinal carcinogenesis. Limitations to this analysis will also be discussed.
    Regulatory Toxicology and Pharmacology 06/2012; 64(1):68-76. DOI:10.1016/j.yrtph.2012.05.019 · 2.14 Impact Factor
  • Source
    • "It has been suggested that such large neutral divergence could be approximated by calculating the distance between expression profiles of randomly chosen pairs of genes from the species compared. The standard approach used to generate random pairs of genes is to permute the orthology relationship between them (Chan et al., 2009; Liao and Zhang, 2006a, b; Xing et al., 2007; Zheng-Bradley et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Motivation: Comparative analyses of gene expression data from different species have become an important component of the study of molecular evolution. Thus methods are needed to estimate evolutionary distances between expression profiles, as well as a neutral reference to estimate selective pressure. Divergence between expression profiles of homologous genes is often calculated with Pearson's or Euclidean distance. Neutral divergence is usually inferred from randomized data. Despite being widely used, neither of these two steps has been well studied. Here, we analyze these methods formally and on real data, highlight their limitations and propose improvements. Results: It has been demonstrated that Pearson's distance, in contrast to Euclidean distance, leads to underestimation of the expression similarity between homologous genes with a conserved uniform pattern of expression. Here, we first extend this study to genes with conserved, but specific pattern of expression. Surprisingly, we find that both Pearson's and Euclidean distances used as a measure of expression similarity between genes depend on the expression specificity of those genes. We also show that the Euclidean distance depends strongly on data normalization. Next, we show that the randomization procedure that is widely used to estimate the rate of neutral evolution is biased when broadly expressed genes are abundant in the data. To overcome this problem, we propose a novel randomization procedure that is unbiased with respect to expression profiles present in the datasets. Applying our method to the mouse and human gene expression data suggests significant gene expression conservation between these species. Contact: marc.robinson-rechavi@unil.ch; sven.bergmann@unil.ch Supplementary information: Supplementary data are available at Bioinformatics online.
    Bioinformatics 05/2012; 28(14):1865-72. DOI:10.1093/bioinformatics/bts266 · 4.62 Impact Factor
Show more