Evidence for the dissemination of cryptic non-coding RNAs transcribed from intronic and intergenic segments by retroposition

Oxford University Press 2013 Bioinformatics Vol.29 No.13

<P><B>Motivation:</B> Insertion of DNA segments is one mechanism by which genomes evolve. The bulk of genomic segments are now known to be transcribed into long and short non-coding RNAs (ncRNAs), promoter-associated transcripts and enhancer-templated transcripts. These various cryptic ncRNAs are thought to be dispersed in the human and other genomes by retroposition.</P><P><B>Results:</B> In this study, I report clear evidence for dissemination of cryptic ncRNAs transcribed from intronic and intergenic segments by retroposition. I used highly stringent conditions to find recently retroposed ncRNAs that had a poly(A) tract and were flanked by target site duplication. I identified 73 instances of retroposition in the human, mouse, and rat genomes (12, 36 and 25 instances, respectively). The inserted segments, in some cases, served as a novel exon or promoter for the associated gene, resulting in novel transcript variants. Some disseminated sequences showed sequence conservation across animals, implying a possible regulatory role. My results indicate that retroposition is one of the mechanisms for dispersion of ncRNAs. I propose that these newly inserted segments may play a role in genome evolution by potentially functioning as novel exons, promoters or enhancers.</P><P><B>Contact:</B> yoonsoo.hahn@gmail.com</P><P><B>Supplementary information:</B> Supplementary data are available at <I>Bioinformatics</I> online.</P>

Anoctamin and transmembrane channel-like proteins are evolutionarily related.

Hahn, Yoonsoo,Kim, Dong Seon,Pastan, Ira H,Lee, Byungkook D.A. Spandidos 2009 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.24 No.1

<P>The anoctamin (ANO) family of proteins, consisting of 10 members in mammals, are transmembrane proteins that have Ca2+-activated Cl- channel activity. The transmembrane channel-like (TMC) family of proteins, consisting of 8 members in mammals, are also transmembrane proteins of which mutations are implicated in various human conditions, such as hearing loss and epidermodysplasia verruciformis. Here we show that ANO and TMC proteins share high sequence similarity and probably the same membrane topology, indicating that these proteins are evolutionarily related. We found many conserved amino acid residues between the two families of proteins, especially in regions spanning the transmembrane domains TM1, TM4-TM5, and TM6-TM7. These findings imply that these proteins form one large family, which we term ANO/TMC superfamily and that TMC proteins also function as channels for Cl- or other ions. The ANO/TMC superfamily proteins are present in almost all diverse groups of eukaryotic organisms, suggesting that the proteins function in important biological processes, such as ion homeostasis, in eukaryotic cells.</P>

Molecular Evolution of TEPP Protein Genes in Metazoans

Springer-Verlag 2009 Biochemical genetics Vol.47 No.9

Genome Sequences of Spinach Deltapartitivirus 1, Spinach Amalgavirus 1, and Spinach Latent Virus Identified in Spinach Transcriptome

( Dongbin Park ),( Yoonsoo Hahn ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.7

Complete genome sequences of three new plant RNA viruses, Spinach deltapartitivirus 1 (SpDPV1), Spinach amalgavirus 1 (SpAV1), and Spinach latent virus (SpLV), were identified from a spinach (Spinacia oleracea) transcriptome dataset. The RNA-dependent RNA polymerases (RdRps) of SpDPV1, SpAV1, and SpLV showed 72%, 53%, and 93% amino acid sequence identities with the homologous RdRp of the most closely related virus, respectively, suggesting that SpDPV1 and SpAV1 were novel viruses. Sequence similarity and phylogenetic analyses revealed that SpDPV1 belonged to the genus Deltapartitivirus of the family Partitiviridae, SpAV1 to the genus Amalgavirus of the family Amalgaviridae, and SpLV to the genus Ilarvirus of the family Bromoviridae. Based on the demarcation criteria, SpDPV1 and SpAV1 are considered as novel species of the genera Deltapartitivirus and Amalgavirus, respectively. This is the first report of these two viruses from spinach.

Genome Sequence of Spinach Cryptic Virus 1, a New Member of the Genus Alphapartitivirus (Family Partitiviridae), Identified in Spinach

( Dongbin Park ),( Yoonsoo Hahn ) 한국미생물 · 생명공학회 2017 Journal of microbiology and biotechnology Vol.27 No.4

A distinct double-stranded RNA (dsRNA) cryptic virus, named spinach cryptic virus 1 (SpCV1), was identified from spinach transcriptome datasets. The SpCV1 genome has two dsRNA genome segments. The larger dsRNA1 has an open reading frame for a conserved RNA-dependent RNA polymerase (RdRp). The smaller dsRNA2 encodes a putative coat protein (CP). The sequence identity of SpCV1 RdRp and CP to the closest cryptic virus is 81% and 60%, respectively. Phylogenetic analysis indicates that SpCV1 is a novel member of the genus Alphapartitivirus (family Partitiviridae).

Quantitative Analysis of RNA Polymerase Slippages for Production of P3N-PIPO Trans-frame Fusion Proteins in Potyvirids

Choi Dongjin,Hahn Yoonsoo 한국미생물학회 2023 The journal of microbiology Vol.61 No.10

Potyvirids, members of the family Potyviridae, produce the P3N-PIPO protein, which is crucial for the cell-to-cell transport of viral genomic RNAs. The production of P3N-PIPO requires an adenine (A) insertion caused by RNA polymerase slippage at a conserved GAA AAA A ( GA6) sequence preceding the PIPO open reading frame. Presently, the slippage rate of RNA polymerase has been estimated in only a few potyvirids, ranging from 0.8 to 2.1%. In this study, we analyzed publicly available plant RNA-seq data and identified 19 genome contigs from 13 distinct potyvirids. We further investigated the RNA polymerase slippage rates at the GA6 motif. Our analysis revealed that the frequency of the A insertion variant ranges from 0.53 to 4.07% in 11 potyviruses (genus Potyvirus). For the two macluraviruses (genus Macluravirus), the frequency of the A insertion variant was found to be 0.72% and 10.96% respectively. Notably, the estimated RNA polymerase slippage rates for 12 out of the 13 investigated potyvirids were reported for the first time in this study. Our findings underscore the value of plant RNA-seq data for quantitative analysis of potyvirid genome variants, specifically at the GA6 slippage site, and contribute to a more comprehensive understanding of the RNA polymerase slippage phenomenon in potyvirids.

Identification of human-specific transcript variants induced by DNA insertions in the human genome.

Kim, Dong Seon,Hahn, Yoonsoo Oxford University Press 2011 Bioinformatics Vol.27 No.1

<P>Many genes in the human genome produce a wide variety of transcript variants resulting from alternative exon splicing, differential promoter usage, or altered polyadenylation site utilization that may function differently in human cells. Here, we present a bioinformatics method for the systematic identification of human-specific novel transcript variants that might have arisen after the human-chimpanzee divergence.</P>

Human-specific protein isoforms produced by novel splice sites in the human genome after the human-chimpanzee divergence

Kim, Dong Seon,Hahn, Yoonsoo BioMed Central 2012 BMC bioinformatics Vol.13 No.-

<P><B>Background</B></P><P>Evolution of splice sites is a well-known phenomenon that results in transcript diversity during human evolution. Many novel splice sites are derived from repetitive elements and may not contribute to protein products. Here, we analyzed annotated human protein-coding exons and identified human-specific splice sites that arose after the human-chimpanzee divergence.</P><P><B>Results</B></P><P>We analyzed multiple alignments of the annotated human protein-coding exons and their respective orthologous mammalian genome sequences to identify 85 novel splice sites (50 splice acceptors and 35 donors) in the human genome. The novel protein-coding exons, which are expressed either constitutively or alternatively, produce novel protein isoforms by insertion, deletion, or frameshift. We found three cases in which the human-specific isoform conferred novel molecular function in the human cells: the human-specific IMUP protein isoform induces apoptosis of the trophoblast and is implicated in pre-eclampsia; the intronization of a part of <I>SMOX</I> gene exon produces inactive spermine oxidase; the human-specific NUB1 isoform shows reduced interaction with ubiquitin-like proteins, possibly affecting ubiquitin pathways.</P><P><B>Conclusions</B></P><P>Although the generation of novel protein isoforms does not equate to adaptive evolution, we propose that these cases are useful candidates for a molecular functional study to identify proteomic changes that might bring about novel phenotypes during human evolution.</P>

Gains of ubiquitylation sites in highly conserved proteins in the human lineage

Kim, Dong Seon,Hahn, Yoonsoo BioMed Central 2012 BMC bioinformatics Vol.13 No.-

<P><B>Background</B></P><P>Post-translational modification of lysine residues of specific proteins by ubiquitin modulates the degradation, localization, and activity of these target proteins. Here, we identified gains of ubiquitylation sites in highly conserved regions of human proteins that occurred during human evolution.</P><P><B>Results</B></P><P>We analyzed human ubiquitylation site data and multiple alignments of orthologous mammalian proteins including those from humans, primates, other placental mammals, opossum, and platypus. In our analysis, we identified 281 ubiquitylation sites in 252 proteins that first appeared along the human lineage during primate evolution: one protein had four novel sites; four proteins had three sites each; 18 proteins had two sites each; and the remaining 229 proteins had one site each. PML, which is involved in neurodevelopment and neurodegeneration, acquired three sites, two of which have been reported to be involved in the degradation of PML. Thirteen human proteins, including ERCC2 (also known as XPD) and NBR1, gained human-specific ubiquitylated lysines after the human-chimpanzee divergence. ERCC2 has a Lys/Gln polymorphism, the derived (major) allele of which confers enhanced DNA repair capacity and reduced cancer risk compared with the ancestral (minor) allele. NBR1 and eight other proteins that are involved in the human autophagy protein interaction network gained a novel ubiquitylation site.</P><P><B>Conclusions</B></P><P>The gain of novel ubiquitylation sites could be involved in the evolution of protein degradation and other regulatory networks. Although gains of ubiquitylation sites do not necessarily equate to adaptive evolution, they are useful candidates for molecular functional analyses to identify novel advantageous genetic modifications and innovative phenotypes acquired during human evolution.</P>

Exon deletion in the MSLN gene encoding MPF/mesothelin precursor protein during Laurasiatherian mammal evolution.

Kim, Dong Seon,Hahn, Yoonsoo D.A. Spandidos 2011 International journal of molecular medicine Vol.27 No.2

<P>Mesothelin is a cell surface glycoprotein that is present in normal mesothelial cells and is highly expressed in several human cancers, including mesotheliomas and ovarian, pancreatic, and lung cancers. The human mesothelin gene (MSLN) encodes a precursor protein, which is processed into 2 mature polypeptides: the N-terminal soluble megakaryocyte-potentiating factor (MPF) and the C-terminal membrane-bound mesothelin which functions as a cell adhesion molecule. In this study, we report the identification and sequence comparison of the MSLN genes in various mammalian species. We found that multiple exon deletion occurred in the Laurasiatherian MSLN genes including 6 exons in the cow, pig, horse, cat, dog, and panda genes and 8 exons in the hedgehog gene. The genomic deletion did not change the open reading frame of the resulting Laurasiatherian MSLN genes, producing internally deleted precursor proteins. The modified precursor was still able to produce the intact cell surface mesothelin protein but would not confer the MPF activity. Genomic sequence comparison showed that a breakage and rejoining event of ancestral introns 2 and 8 was responsible for the deletion. The present findings support that exon deletion is one of the molecular mechanisms underlying gene evolution in mammalian genomes.</P>