Dataset Information

Urochordate serpins are Classified into Six Groups Encoded by Exon-Intron Structures, Microsynteny and Bayesian Phylogenetic Analyses.

ABSTRACT: Members of serpin superfamily are involved in wide array of cellular processes to control proteolytic activities of eukaryotic organisms. Vertebrate serpins are extensively studied and reported to be classified into six groups (V1-V6) based on gene structures. However, there is no study conducted for serpins in urochordates (the closest living invertebrates related to vertebrates) to date. To unravel further the phylogenetic history of serpin genes, we characterized serpin genes from two urochordates (Ciona intestinalis and Ciona savignyi). There are 11 and 5 serpins in the C. intestinalis and C. savignyi, respectively. The exon/intron structures and genomic locus comparisons together with sequence phylogenetic analysis, suggested that urochordate serpins are classified into six groups (U1-U6), different from six groups (V1-V6) of vertebrate serpins. Human ?1-antitrypsin shared lower sequence identities and similarities with urochordates serpins ranged from 14-29% and 30-49%, respectively. Based on protein sequences, genes and genomic architectures, we conclude that these two urochordates do not contain a single copy of genuine ortholog of the vertebrate serpins.

SUBMITTER: Kumar A

PROVIDER: S-EPMC4150122 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Urochordate serpins are Classified into Six Groups Encoded by Exon-Intron Structures, Microsynteny and Bayesian Phylogenetic Analyses.

Kumar Abhishek A Bhandari Anita A

Journal of genomics 20140901

Members of serpin superfamily are involved in wide array of cellular processes to control proteolytic activities of eukaryotic organisms. Vertebrate serpins are extensively studied and reported to be classified into six groups (V1-V6) based on gene structures. However, there is no study conducted for serpins in urochordates (the closest living invertebrates related to vertebrates) to date. To unravel further the phylogenetic history of serpin genes, we characterized serpin genes from two urochor ...[more]

PMID: 25184006

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Project description:BACKGROUND:In-depth study of the intron retention levels of transcripts provide insights on the mechanisms regulating pre-mRNA splicing efficiency. Additionally, detailed analysis of retained introns can link these introns to post-transcriptional regulation or identify aberrant splicing events in human diseases. RESULTS:We present IntEREst, Intron-Exon Retention Estimator, an R package that supports rigorous analysis of non-annotated intron retention events (in addition to the ones annotated by RefSeq or similar databases), and support intra-sample in addition to inter-sample comparisons. It accepts binary sequence alignment/map (.bam) files as input and determines genome-wide estimates of intron retention or exon-exon junction levels. Moreover, it includes functions for comparing subsets of user-defined introns (e.g. U12-type vs U2-type) and its plotting functions allow visualization of the distribution of the retention levels of the introns. Statistical methods are adapted from the DESeq2, edgeR and DEXSeq R packages to extract the significantly more or less retained introns. Analyses can be performed either sequentially (on single core) or in parallel (on multiple cores). We used IntEREst to investigate the U12- and U2-type intron retention in human and plant RNAseq dataset with defects in the U12-dependent spliceosome due to mutations in the ZRSR2 component of this spliceosome. Additionally, we compared the retained introns discovered by IntEREst with that of other methods and studies. CONCLUSION:IntEREst is an R package for Intron retention and exon-exon junction levels analysis of RNA-seq data. Both the human and plant analyses show that the U12-type introns are retained at higher level compared to the U2-type introns already in the control samples, but the retention is exacerbated in patient or plant samples carrying a mutated ZRSR2 gene. Intron retention events caused by ZRSR2 mutation that we discovered using IntEREst (DESeq2 based function) show considerable overlap with the retained introns discovered by other methods (e.g. IRFinder and edgeR based function of IntEREst). Our results indicate that increase in both the number of biological replicates and the depth of sequencing library promote the discovery of retained introns, but the effect of library size gradually decreases with more than 35 million reads mapped to the introns.

Project description:A typical eukaryotic gene is comprised of alternating stretches of regions, exons and introns, retained in and spliced out a mature mRNA, respectively. Although the length of introns may vary substantially among organisms, a large fraction of genes contains short introns in many species. Notably, some Ciliates (Paramecium and Nyctotherus) possess only ultra-short introns, around 25 bp long. In Paramecium, ultra-short introns with length divisible by three (3n) are under strong evolutionary pressure and have a high frequency of in-frame stop codons, which, in the case of intron retention, cause premature termination of mRNA translation and consequent degradation of the mis-spliced mRNA by the nonsense-mediated decay mechanism. Here, we analyzed introns in five genera of Ciliates, Paramecium, Tetrahymena, Ichthyophthirius, Oxytricha, and Stylonychia. Introns can be classified into two length classes in Tetrahymena and Ichthyophthirius (with means 48 bp, 69 bp, and 55 bp, 64 bp, respectively), but, surprisingly, comprise three distinct length classes in Oxytricha and Stylonychia (with means 33-35 bp, 47-51 bp, and 78-80 bp). In most ranges of the intron lengths, 3n introns are underrepresented and have a high frequency of in-frame stop codons in all studied species. Introns of Paramecium, Tetrahymena, and Ichthyophthirius are preferentially located at the 5' and 3' ends of genes, whereas introns of Oxytricha and Stylonychia are strongly skewed towards the 5' end. Analysis of evolutionary conservation shows that, in each studied genome, a significant fraction of intron positions is conserved between the orthologs, but intron lengths are not correlated between the species. In summary, our study provides a detailed characterization of introns in several genera of Ciliates and highlights some of their distinctive properties, which, together, indicate that splicing spellchecking is a universal and evolutionarily conserved process in the biogenesis of short introns in various representatives of Ciliates.

Dataset Information

Urochordate serpins are Classified into Six Groups Encoded by Exon-Intron Structures, Microsynteny and Bayesian Phylogenetic Analyses.

Publications

Urochordate serpins are Classified into Six Groups Encoded by Exon-Intron Structures, Microsynteny and Bayesian Phylogenetic Analyses.

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