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1.
Nucleic Acids Res ; 48(11): 5926-5938, 2020 06 19.
Article in English | MEDLINE | ID: mdl-32421815

ABSTRACT

Alternative polyadenylation (APA) produces isoforms with distinct 3'-ends, yet their functional differences remain largely unknown. Here, we introduce the APA-seq method to detect the expression levels of APA isoforms from 3'-end RNA-Seq data by exploiting both paired-end reads for gene isoform identification and quantification. We detected the expression levels of APA isoforms in individual Caenorhabditis elegans embryos at different stages throughout embryogenesis. Examining the correlation between the temporal profiles of isoforms led us to distinguish two classes of genes: those with highly correlated isoforms (HCI) and those with lowly correlated isoforms (LCI) across time. We hypothesized that variants with similar expression profiles may be the product of biological noise, while the LCI variants may be under tighter selection and consequently their distinct 3' UTR isoforms are more likely to have functional consequences. Supporting this notion, we found that LCI genes have significantly more miRNA binding sites, more correlated expression profiles with those of their targeting miRNAs and a relative lack of correspondence between their transcription and protein abundances. Collectively, our results suggest that a lack of coherence among the regulation of 3' UTR isoforms is a proxy for selective pressures acting upon APA usage and consequently for their functional relevance.


Subject(s)
3' Untranslated Regions/genetics , Caenorhabditis elegans/embryology , Caenorhabditis elegans/genetics , Gene Expression Regulation, Developmental , Poly A/analysis , Polyadenylation , Animals , Drosophila melanogaster , Embryonic Development/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Nucleic Acid Conformation , Xenopus laevis
3.
Nature ; 531(7596): 637-641, 2016 Mar 31.
Article in English | MEDLINE | ID: mdl-26886793

ABSTRACT

Animals are grouped into ~35 'phyla' based upon the notion of distinct body plans. Morphological and molecular analyses have revealed that a stage in the middle of development--known as the phylotypic period--is conserved among species within some phyla. Although these analyses provide evidence for their existence, phyla have also been criticized as lacking an objective definition, and consequently based on arbitrary groupings of animals. Here we compare the developmental transcriptomes of ten species, each annotated to a different phylum, with a wide range of life histories and embryonic forms. We find that in all ten species, development comprises the coupling of early and late phases of conserved gene expression. These phases are linked by a divergent 'mid-developmental transition' that uses species-specific suites of signalling pathways and transcription factors. This mid-developmental transition overlaps with the phylotypic period that has been defined previously for three of the ten phyla, suggesting that transcriptional circuits and signalling mechanisms active during this transition are crucial for defining the phyletic body plan and that the mid-developmental transition may be used to define phylotypic periods in other phyla. Placing these observations alongside the reported conservation of mid-development within phyla, we propose that a phylum may be defined as a collection of species whose gene expression at the mid-developmental transition is both highly conserved among them, yet divergent relative to other species.


Subject(s)
Body Patterning , Embryonic Development , Phylogeny , Animals , Body Patterning/genetics , Conserved Sequence/genetics , Embryonic Development/genetics , Evolution, Molecular , Gene Expression Regulation, Developmental , Gene Regulatory Networks , Genes, Developmental/genetics , Models, Biological , Phenotype , Species Specificity , Transcriptome/genetics
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