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Dev Cell
2011 Apr 19;204:483-96. doi: 10.1016/j.devcel.2011.03.015.
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Mapping gene expression in two Xenopus species: evolutionary constraints and developmental flexibility.
Yanai I
,
Peshkin L
,
Jorgensen P
,
Kirschner MW
.
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Changes in gene expression are thought to be important for morphological evolution, though little is known about the nature or magnitude of the differences. Here, we examine Xenopus laevis and Xenopus tropicalis, two amphibians with very similar development, and ask how their transcriptomes compare. Despite separation for ~30-90 million years, there is strong conservation in gene expression in the vast majority of the expressed orthologs. Significant changes occur in the level of gene expression but changes in the timing of expression (heterochrony) were much less common. Differences in level were concentrated in the earliest embryonic stages. Changes in timing were prominently found in pathways that respond to selective features of the environment. We propose that different evolutionary rates across developmental stages may be explained by the stabilization of cell fate determination in the later stages.
Figure 1. Comparative Transcriptomics of Xenopus Development(A) Developmental stages assayed in this study, taken from Nieuwkoop and Faber (1994).(B) Microarray gene expression data for the eight indicated genes. For each gene, the nine profiles (three clutches across three probes) are shown for both X. laevis (blue) and X. tropicalis (green). The y axis indicates log10 relative concentrations of mRNA abundance (see Experimental Procedures). Also indicated for each gene is its EDi, a metric for divergence explained in the text.(C) Summary of 20 gene expression clusters for X. laevis (left). Clusters were generated using QT clustering (Heyer et al., 1999) with a maximum correlation distance of 0.85. Each summary profile is the mean of the member profiles, normalized by dividing by the maximum value. The average profile of the X. tropicalis orthologs in these same clusters are shown to the right. Orthologous clusters share the same color across plots.
Figure 2. Dominant Signal of Gene Expression Conservation between the SpeciesDistributions of correlation coefficients when different classes of transcriptomes are compared. Dark red distributions indicate the median correlations between expression profiles of different probes (within the same clutch). Bright blue distributions indicate distributions of median correlations of expression profiles across clutches (within the same probes). These distributions are shifted toward higher correlations with respect to the distribution of median pairwise correlations between species (black) and randomly paired X. laevis and X. tropicalis genes (dashed line). Since this analysis tests the reproducibility of the data, we limited it to those genes showing dynamic expression in the developmental time course of either species (see Experimental Procedures).
Figure 3. Conservation and Divergence across Pathways(A) Expression divergence (EDi) distributions across functional gene sets and indicated by different colors. The y axis indicates the normalized frequency. The black plot indicates the normalized distribution of divergences for all genes. A shift to the left/right indicates enrichment for conservation/divergence, respectively.(B–D) Expression profiles of genes involved in the alternative pathway of the complement system (B), hatching enzymes (C), and oxygen-binding genes (D). See Figure S3B for additional heterochrony in members of the membrane attack complex. Expression profiles are shown in log10 relative concentrations as in Figure 1.
Figure 4. Heterochrony and Heterometry in Gene Expression Evolution(A) A sigmoid is defined by b1, t1, h0, and h1 (see text).(B) The ORAI2 gene expression profiles (log10 relative concentrations) in both X. laevis and X. tropicalis is shown fitted by sigmoids.(C) Plots of t1 (time of induction) for pairs of genes with >0.8 goodness of fit in both species. The green line is unity and the red is fitted to the data.(D) Plots of h1 (range of expression). Same format as (C).(E and F) Heterochrony/heterometry phase-plane for families of transcription factors (E) and several signaling pathways (F). The circles and lines indicate the mean and standard deviation of each gene set's heterochronies and heterometries. The transcription factor families are helix-loop-helix (PF00010, 27 genes with sigmoids), Homeobox (IPR001356, 74 genes), Zinc finger (C2H2 type, IPR007087, 24 genes), T-box (IPR001699, 5 genes), Fox head (IPR001766, 16 genes), and HMG (IPR000910, 8 genes). The signaling pathways are Wnt receptor (GO:0016055, 18 genes with sigmoids), transforming growth factor beta receptor (GO:0007179, 13 genes), Hedgehog (GO:0007224, 6 genes), Transmembrane receptor protein tyrosine kinase (GO:0007169, 17 genes), Notch (GO:0007219, 9 genes), Apoptosis (GO:0006917, 40 genes), and G protein-coupled receptor protein (GO:0007186, 73 genes).
Figure 5. Global Comparison of the X. laevis and X. tropicalis Developmental Transcriptomes(A–C) The heat maps represent the fraction of genes significantly different between pairs of transcriptomes; the grid separates the replicates across the stages. The color of each square indicates the difference at the specified developmental stages. (A) and (B) represent X. tropicalis and X. laevis plotted against themselves.(C) X. tropicalis plotted against X. laevis. The diagonal squares by definition have zero divergence. The fraction is computed as the number of genes with a difference of at least 1.5 log10 units out of the number of genes with a maximum expression of at least 2.5 log10 units in either transcriptomes.(D) For 2297 dynamically expressed genes, the plot indicates the number of genes with significantly different transcript abundance (>1.5 log10).
Figure 6. Comparison of the Maternal Transcriptomes of X. laevis and X. tropicalis(A) For each of four functional gene sets, the plot compares the expression levels (log10 relative concentrations) in stage 2 embryos between the two species.(B) Comparative gene expression profiles of four keratin genes. These genes are less than 80% identical at the protein level allowing good resolution by the microarray data. KRT24 in X. tropicalis exhibits two patterns depending upon the probes examined: one with maternal expression and another with a profile heterochronic to the X. laevis ortholog.(C) Comparative gene expression profiles of four retinol dehydrogenases.
Ambros,
MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing.
2003, Pubmed
Ambros,
MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing.
2003,
Pubmed
Arthur,
The concept of developmental reprogramming and the quest for an inclusive theory of evolutionary mechanisms.
2000,
Pubmed
Baldessari,
Global gene expression profiling and cluster analysis in Xenopus laevis.
2005,
Pubmed
,
Xenbase
Barreiro,
From evolutionary genetics to human immunology: how selection shapes host defence genes.
2010,
Pubmed
Bisbee,
Albumin phylogeny for clawed frogs (Xenopus).
1977,
Pubmed
,
Xenbase
Blekhman,
Gene regulation in primates evolves under tissue-specific selection pressures.
2008,
Pubmed
Borza,
Atlantic cod (Gadus morhua) hemoglobin genes: multiplicity and polymorphism.
2009,
Pubmed
Britten,
Repetitive and non-repetitive DNA sequences and a speculation on the origins of evolutionary novelty.
1971,
Pubmed
Carroll,
Hatching in the toad Xenopus laevis: morphological events and evidence for a hatching enzyme.
1974,
Pubmed
,
Xenbase
Carroll,
Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution.
2008,
Pubmed
Cole,
Beyond lysis: how complement influences cell fate.
2003,
Pubmed
Davidson,
Gene regulatory networks.
2005,
Pubmed
Domazet-Lošo,
A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns.
2010,
Pubmed
Eroshkin,
Multiple noggins in vertebrate genome: cloning and expression of noggin2 and noggin4 in Xenopus laevis.
2006,
Pubmed
,
Xenbase
Evans,
A mitochondrial DNA phylogeny of African clawed frogs: phylogeography and implications for polyploid evolution.
2004,
Pubmed
,
Xenbase
Fletcher,
Expression of Xenopus tropicalis noggin1 and noggin2 in early development: two noggin genes in a tetrapod.
2004,
Pubmed
,
Xenbase
Fletcher,
FGF8 spliceforms mediate early mesoderm and posterior neural tissue formation in Xenopus.
2006,
Pubmed
,
Xenbase
Gerhart,
1998 Warkany lecture: signaling pathways in development.
1999,
Pubmed
Hellsten,
Accelerated gene evolution and subfunctionalization in the pseudotetraploid frog Xenopus laevis.
2007,
Pubmed
,
Xenbase
Hellsten,
The genome of the Western clawed frog Xenopus tropicalis.
2010,
Pubmed
,
Xenbase
Heyer,
Exploring expression data: identification and analysis of coexpressed genes.
1999,
Pubmed
Jorgensen,
The mechanism and pattern of yolk consumption provide insight into embryonic nutrition in Xenopus.
2009,
Pubmed
,
Xenbase
Kalinka,
Gene expression divergence recapitulates the developmental hourglass model.
2010,
Pubmed
Khaitovich,
Evolution of primate gene expression.
2006,
Pubmed
Khaitovich,
A neutral model of transcriptome evolution.
2004,
Pubmed
King,
Evolution at two levels in humans and chimpanzees.
1975,
Pubmed
Kloosterman,
Substrate requirements for let-7 function in the developing zebrafish embryo.
2004,
Pubmed
Knöchel,
Globin evolution in the genus Xenopus: comparative analysis of cDNAs coding for adult globin polypeptides of Xenopus borealis and Xenopus tropicalis.
1986,
Pubmed
,
Xenbase
McLin,
Expression of complement components coincides with early patterning and organogenesis in Xenopus laevis.
2008,
Pubmed
,
Xenbase
Nolte,
Divergence in gene regulation at young life history stages of whitefish (Coregonus sp.) and the emergence of genomic isolation.
2009,
Pubmed
Pasquinelli,
Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.
2000,
Pubmed
RUUD,
Vertebrates without erythrocytes and blood pigment.
1954,
Pubmed
Renaut,
Gene expression divergence and hybrid misexpression between lake whitefish species pairs (Coregonus spp. Salmonidae).
2009,
Pubmed
Rifkin,
Evolution of gene expression in the Drosophila melanogaster subgroup.
2003,
Pubmed
Roush,
The let-7 family of microRNAs.
2008,
Pubmed
Schmidt,
Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding.
2010,
Pubmed
Schmidt,
Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia.
2004,
Pubmed
Showell,
Natural mating and tadpole husbandry in the western clawed frog Xenopus tropicalis.
2009,
Pubmed
,
Xenbase
Staubach,
A test of the neutral model of expression change in natural populations of house mouse subspecies.
2010,
Pubmed
Subramanian,
Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles.
2005,
Pubmed
Voight,
A map of recent positive selection in the human genome.
2006,
Pubmed
Watanabe,
Stage-specific expression of microRNAs during Xenopus development.
2005,
Pubmed
,
Xenbase
Xie,
Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species.
2010,
Pubmed
Yanai,
Comparison of diverse developmental transcriptomes reveals that coexpression of gene neighbors is not evolutionarily conserved.
2009,
Pubmed
Yanai,
Similar gene expression profiles do not imply similar tissue functions.
2006,
Pubmed
,
Xenbase
Yanai,
Incongruent expression profiles between human and mouse orthologous genes suggest widespread neutral evolution of transcription control.
2004,
Pubmed