A quantitative model for characterizing the evolutionary history of mammalian gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mustela putorius furo Canis lupus familiaris Oryctolagus cuniculus Dasypus novemcinctus Monodelphis domestica
PROVIDER: GSE106077 | GEO | 2018/10/21
REPOSITORIES: GEO
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2014-08-06 | GSE57438 | GEO
Project description:This set of arrays contains all microarray experiments done involving comparisons among C. elegans natural isolates and mutation-accumulation lines. Abstract: The evolutionary importance of gene-expression divergence is unclear: some studies suggest that it is an important mechanism for evolution by natural selection, whereas others claim that most between-species regulatory changes are neutral or nearly neutral. We examined global transcriptional divergence patterns in a set of Caenorhabditis elegans mutation-accumulation lines and natural isolate lines to provide insights into the evolutionary importance of transcriptional variation and to discriminate between the forces of mutation and natural selection in shaping the evolution of gene expression. We detected the effects of selection on transcriptional divergence patterns and characterized them with respect to coexpressed gene sets, chromosomal clustering of expression changes and functional gene categories. We directly compared observed transcriptional variation patterns in the mutation-accumulation and natural isolate lines to a neutral model of transcriptome evolution to show that strong stabilizing selection dominates the evolution of transcriptional change for thousands of C. elegans expressed sequences. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Computed
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Project description:Many normal tissues undergo age-related DNA methylation drift providing a quantitative measure of tissue age. However this drift has not been demonstrated in neoplastic tissues. Here we identify and validate 781 CpG-islands (CGIs) that undergo significant methylomic drift in normal colorectal tissues continue to drift in neoplasia and remain significantly correlated with one another across tissue samples. However compared with normal colon this drift advances (~3-4 fold) faster in neoplasia consistent with increased cell proliferation during neoplastic progression. Furthermore we show that the observed drift patterns are broadly consistent with modeled adenoma-carcinoma sojourn time distributions from colorectal cancer (CRC) incidence data. These results support the hypothesis that beginning with the founder premalignant cell cancer precursors frequently sojourn for decades before turning into cancer which implies that the founder cell typically arises early in life. We estimate that at least 77-89% of the observed drift variance in distal and rectal tumors is explained by stochastic variability associated with neoplastic progression while only 55% of the variance is explained for proximal tumors. However >50% of identified gene-CGI pairs in the proximal colon that undergo drift are significantly and mainly negatively correlated with cancer gene expression suggesting that methylomic drift participates in the clonal evolution of CRCs. Significance: Methylomic drift advances in colorectal neoplasia consistent with extended sojourn time distributions explaining a significant fraction of epigenetic heterogeneity in CRCs. Importantly the estimated long-duration premalignant sojourn times suggest that early dietary and lifestyle interventions may be more effective than later changes in reducing CRC incidence.
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Project description:This set of arrays contains all microarray experiments done involving comparisons among C. elegans natural isolates and mutation-accumulation lines. Abstract: The evolutionary importance of gene-expression divergence is unclear: some studies suggest that it is an important mechanism for evolution by natural selection, whereas others claim that most between-species regulatory changes are neutral or nearly neutral. We examined global transcriptional divergence patterns in a set of Caenorhabditis elegans mutation-accumulation lines and natural isolate lines to provide insights into the evolutionary importance of transcriptional variation and to discriminate between the forces of mutation and natural selection in shaping the evolution of gene expression. We detected the effects of selection on transcriptional divergence patterns and characterized them with respect to coexpressed gene sets, chromosomal clustering of expression changes and functional gene categories. We directly compared observed transcriptional variation patterns in the mutation-accumulation and natural isolate lines to a neutral model of transcriptome evolution to show that strong stabilizing selection dominates the evolution of transcriptional change for thousands of C. elegans expressed sequences. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Keywords: all_pairs
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Project description:Transcriptional regulatory changes have been shown to contribute to phenotypic differences between species, but many questions remain about how gene expression evolves. Here we report the first comparative study of nascent transcription in primates. We used PRO-seq to map actively transcribing RNA polymerases in resting and activated CD4+ T-cells in multiple human, chimpanzee, and rhesus macaque individuals, with rodents as outgroups. This approach allowed us to directly measure active transcription separately from post-transcriptional processes. We observed general conservation in coding and non-coding transcription, punctuated by numerous differences between species, particularly at distal enhancers and non-coding RNAs. Transcription factor binding sites are a primary determinant of transcriptional differences between species. We found evidence for stabilizing selection on gene expression levels and adaptive substitutions associated with lineage-specific transcription. Finally, rates of evolutionary change are strongly correlated with long-range chromatin interactions. These observations clarify the role of primary transcription in regulatory evolution.
2016-12-29 | GSE85337 | GEO
Project description:The spatiotemporal control of gene expression exerted by promoters and enhancers is central for organismal development, physiology and behaviour. These two types of regulatory elements have long been distinguished from each other based on their function, but recent work highlighted common architectural and functional features. It also suggested that inheritable alterations in the epigenetic and sequence context of regulatory elements might underlie evolutionary changes of their principal activity, which could result in changes in the transcriptional profile of genes under their control or even facilitate the birth of new genes. Here, based on integrated cross-mammalian analyses of DNase hypersensitivity, chromatin modification and transcriptional data, we provide support for this hypothesis by detecting 445 regulatory elements with signatures of activity turnover in sister species from the primate and rodent lineages (termed "P/E" elements). Through the comparison with outgroup species, we defined the directionality of turnover events, which revealed that most instances represent transformations of putative ancestral enhancers into promoters, leading to the emergence of species-specific transcribed loci or 5' exons. Notably, P/E elements have distinct GC sequence compositions and stabilizing 5' splicing (U1) regulatory motif patterns, which may predispose them to functional repurposing during evolution. Moreover, we trace changes in the U1 and polyadenylation signal densities and distributions that accompanied and likely drove the evolutionary activity switches. Overall, our work highlights functional repurposing as a notable mechanism that likely facilitated regulatory innovation and the origination of new genes and exons during mammalian evolution.
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Project description:Genetic drift and selection in Drosophila
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Project description:Inter-individual variation in gene regulation has been shown to be heritable and it is quite often associated with differences in disease susceptibility between individuals. While many human studies focused on mapping associations between genetic and gene regulatory variation, much less attention has been paid to the evolutionary processes that shape the observed differences in gene regulation between individuals in humans or any other primate. To begin addressing this gap, we performed a comparative expression quantitative trait loci (eQTL) mapping study in humans and chimpanzees, using gene expression data from primary heart samples. While expression variability in both species is strongly determined by non-genetic sources, such as cell type heterogeneity, we found evidence that the degree of inter-individual variation in gene regulation is generally conserved in humans and chimpanzees. In particular, we found a significant overlap of genes associated with eQTLs in the two species. We conclude that humans and chimpanzees share sources common determinants of gene expression variability, including genetically regulated constraints from stabilizing and diversifying selection pressures.
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2010-10-01 | GSE23857 | GEO
Project description:Here we studied Vanessa cardui, the species with the widest diet breadth among butterflies and a potential insect pest, by comparing tissue-specific transcriptomes from caterpillars that were fed six different host plants. We tested whether the similarities of gene-expression response reflect the evolutionary history of adaptation to these plants in the Vanessa and related genera, against the null hypothesis of transcriptional profiles reflecting plant phylogenetic relatedness. Science for Life Laboratory (SciLifeLab, Sweden) conducted the sequencing of RNA samples. The cDNA libraries (Illumina TruSeq RNA) were sequenced using the Illumina HiSeq 2000 platform using 100-bp paired-end sequencing. We obtained more than 9 million read-pairs from seventy one cDNA libraries sequenced and the transcriptome assembly (TA) of these sequences resulted in 213, 237 transcripts (162,189 components) with a contig N50 of 2,193 bp. Thus, we covered approximately 300x the transcriptome of caterpillars of the species V. cardui.
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