scholarly journals Intron gain by tandem genomic duplication: a novel case in a potato gene encoding RNA-dependent RNA polymerase

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2272 ◽  
Author(s):  
Ming-Yue Ma ◽  
Xin-Ran Lan ◽  
Deng-Ke Niu

The origin and subsequent accumulation of spliceosomal introns are prominent events in the evolution of eukaryotic gene structure. However, the mechanisms underlying intron gain remain unclear because there are few proven cases of recently gained introns. In anRNA-dependent RNA polymerase(RdRp) gene, we found that a tandem duplication occurred after the divergence of potato and its wild relatives among otherSolanumplants. The duplicated sequence crosses the intron-exon boundary of the first intron and the second exon. A new intron was detected at this duplicated region, and it includes a small previously exonic segment of the upstream copy of the duplicated sequence and the intronic segment of the downstream copy of the duplicated sequence. The donor site of this new intron was directly obtained from the small previously exonic segment. Most of the splicing signals were inherited directly from the parental intron/exon structure, including a putative branch site, the polypyrimidine tract, the 3′ splicing site, two putative exonic splicing enhancers, and the GC contents differed between the intron and exon. In the widely cited model of intron gain by tandem genomic duplication, the duplication of an AGGT-containing exonic segment provides the GT and AG splicing sites for the new intron. Our results illustrate that the tandem duplication model of intron gain should be diverse in terms of obtaining the proper splicing signals.

2016 ◽  
Author(s):  
Ming-Yue Ma ◽  
Xin-Ran Lan ◽  
Deng-Ke Niu

Origin and subsequent accumulation of spliceosomal introns are prominent events in the evolution of eukaryotic gene structure. Recently gained introns would be especially useful for the study of the mechanisms of intron gain because randomly accumulated mutations might erase the evolutionary traces. The mechanisms of intron gain remain unclear due to the presence of very few solid cases. A widely cited model of intron gain is tandem genomic duplication, in which the duplication of an AGGT-containing exonic segment provides the GT and AG splicing sites for the new intron. We found that the second intron of the potato RNA-dependent RNA polymerase gene PGSC0003DMG402000361 originated mainly from a direct duplication of the 3′ side of the upstream intron. The 5' splicing site of this new intron was recruited from the upstream exonic sequence. In addition to the new intron, a downstream exonic segment of 178 bp also arose from duplication. Most of the splicing signals were inherited directly from the parental intron/exon structure, including a putative branch site, the polypyrimidine tract, the 3′ splicing site, two putative exonic splicing enhancers and the GC contents differentiated between the intron and exon. We propose a new version of the tandem genomic duplication model, termed as the partial duplication of the preexisting intron/exon structure. This new version and the widely cited version are not mutually exclusive.


2015 ◽  
Author(s):  
Ming-Yue Ma ◽  
Deng-Ke Niu

Origin and subsequent accumulation of spliceosomal introns are prominent events in the evolution of eukaryotic gene structure. Recently gained introns would be especially useful for the study of the mechanism(s) of intron gain because the evolutionary traces might have not been erased by randomly accumulated mutations. However, the mechanism(s) of intron gain remain unclear due to the presence of a few solid cases. A widely cited model of intron gain is tandem genomic duplication, in which the duplication of an AGGT-containing exonic segment provides the GT and AG splicing sites for the new intron. However, successful recognition and splicing of an intron require many more signals than those at the two splicing sites. We found that the second intron of the potato RNA-dependent RNA polymerase gene PGSC0003DMG402000361 is absent in the orthologous genes of other Solanaceae plants, and sequence similarity showed that the major part of the new intron is a direct duplication of the 3' side of the upstream intron. In addition to the new intron, a downstream exonic segment of 168bp has also been duplicated. Most of the splicing signals were inherited from the parental intron/exon structure, including a putative branch site, the polypyrimidine tract, the 3' splicing site, two putative exonic splicing enhancers and the GC contents differentiated between the intron and exon. We propose a modified version of the tandem genomic duplication model, termed as the partial duplication of the preexisting intron/exon structure.


2016 ◽  
Author(s):  
Ming-Yue Ma ◽  
Xin-Ran Lan ◽  
Deng-Ke Niu

Origin and subsequent accumulation of spliceosomal introns are prominent events in the evolution of eukaryotic gene structure. Recently gained introns would be especially useful for the study of the mechanisms of intron gain because randomly accumulated mutations might erase the evolutionary traces. The mechanisms of intron gain remain unclear due to the presence of very few solid cases. A widely cited model of intron gain is tandem genomic duplication, in which the duplication of an AGGT-containing exonic segment provides the GT and AG splicing sites for the new intron. We found that the second intron of the potato RNA-dependent RNA polymerase gene PGSC0003DMG402000361 originated mainly from a direct duplication of the 3′ side of the upstream intron. The 5' splicing site of this new intron was recruited from the upstream exonic sequence. In addition to the new intron, a downstream exonic segment of 178 bp also arose from duplication. Most of the splicing signals were inherited directly from the parental intron/exon structure, including a putative branch site, the polypyrimidine tract, the 3′ splicing site, two putative exonic splicing enhancers and the GC contents differentiated between the intron and exon. We propose a new version of the tandem genomic duplication model, termed as the partial duplication of the preexisting intron/exon structure. This new version and the widely cited version are not mutually exclusive.


2020 ◽  
Author(s):  
Shruti Koulgi ◽  
Vinod Jani ◽  
Mallikarjunachari Uppuladinne V N ◽  
Uddhavesh Sonavane ◽  
Rajendra Joshi

<p>The efforts towards developing a potential drug against the current global pandemic, COVID-19, has increased in the past few months. Drug development strategies to target the RNA dependent RNA polymerase (RdRP) are being tried worldwide. The gene encoding this protein, is known to be conserved amongst positive strand RNA viruses. This enables an avenue to repurpose the drugs designed against earlier reported inhibitors of RdRP. One such strong inhibitor is remdesivir which has been used against EBOLA infections. The binding of remdesivir to RdRP of SARS-CoV-2 has been studied using the classical molecular dynamics and ensemble docking approach. A comparative study of the simulations of RdRP in the apo and remdesivir-bound form revealed blocking of the template entry site in the presence of remdesivir. The conformation changes leading to this event were captured through principal component analysis. The conformational and thermodynamic parameters supported the experimental information available on the involvement of crucial arginine, serine and aspartate residues belonging to the conserved motifs in RdRP functioning. The catalytic site comprising of SER 759, ASP 760, and ASP 761 (SDD) was observed to form strong contacts with remdesivir. The significantly strong interactions of these residues with remdesivir may infer the latter’s binding similar to the normal nucleotides thereby remaining unidentified by the exonuclease activity of RdRP. The ensemble docking of remdesivir too, comprehended the involvement of similar residues in interaction with the inhibitor. This information on crucial interactions between conserved residues of RdRP with remdesivir through <i>in-silico</i> approaches may be useful in designing inhibitors.<b></b></p>


2020 ◽  
Author(s):  
Shruti Koulgi ◽  
Vinod Jani ◽  
Mallikarjunachari Uppuladinne V N ◽  
Uddhavesh Sonavane ◽  
Rajendra Joshi

<p>The efforts towards developing a potential drug against the current global pandemic, COVID-19, has increased in the past few months. Drug development strategies to target the RNA dependent RNA polymerase (RdRP) are being tried worldwide. The gene encoding this protein, is known to be conserved amongst positive strand RNA viruses. This enables an avenue to repurpose the drugs designed against earlier reported inhibitors of RdRP. One such strong inhibitor is remdesivir which has been used against EBOLA infections. The binding of remdesivir to RdRP of SARS-CoV-2 has been studied using the classical molecular dynamics and ensemble docking approach. A comparative study of the simulations of RdRP in the apo and remdesivir-bound form revealed blocking of the template entry site in the presence of remdesivir. The conformation changes leading to this event were captured through principal component analysis. The conformational and thermodynamic parameters supported the experimental information available on the involvement of crucial arginine, serine and aspartate residues belonging to the conserved motifs in RdRP functioning. The catalytic site comprising of SER 759, ASP 760, and ASP 761 (SDD) was observed to form strong contacts with remdesivir. The significantly strong interactions of these residues with remdesivir may infer the latter’s binding similar to the normal nucleotides thereby remaining unidentified by the exonuclease activity of RdRP. The ensemble docking of remdesivir too, comprehended the involvement of similar residues in interaction with the inhibitor. This information on crucial interactions between conserved residues of RdRP with remdesivir through <i>in-silico</i> approaches may be useful in designing inhibitors.<b></b></p>


2009 ◽  
Vol 22 (10) ◽  
pp. 1312-1318 ◽  
Author(s):  
Farshad Rakhshandehroo ◽  
Minoru Takeshita ◽  
Julie Squires ◽  
Peter Palukaitis

The gene encoding RNA-dependent RNA polymerase 1 (RDR1) is involved in basal resistance to several viruses. Expression of the RDR1 gene also is induced in resistance to Tobacco mosaic virus (TMV) mediated by the N gene in tobacco (Nicotiana tabacum cv. Samsun NN) in an incompatible hypersensitive response, as well as in a compatible response against Potato virus Y (PVY). Reducing the accumulation of NtRDR1 transcripts by RNA inhibition mediated by transgenic expression of a double-stranded RNA hairpin corresponding to part of the RDR1 gene resulted in little or no induction of accumulation of RDR1 transcripts after infection by PVY. Plants with lower accumulation of RDR1 transcripts showed much higher accumulation levels of PVY. Reduced accumulation of NtRDR1 transcripts also resulted in lower or no induced expression of three other antiviral, defense-related genes after infection by PVY. These genes encoded a mitochondrial alternative oxidase, an inhibitor of virus replication (IVR), and a transcription factor, ERF5, all involved in resistance to infection by TMV, as well as RDR6, involved in RNA silencing. The extent of the effect on the induced NtIVR and NtERF5 genes correlated with the extent of suppression of the NtRDR1 gene.


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