Exploring the selective constraint on the sizes of insertions and deletions in 5' untranslated regions in mammals

Chen, Chun-Hsi; Liao, Ben-Yang; Chen, Feng‐Chi

doi:10.1186/1471-2148-11-192

Cited by 11 publications

(10 citation statements)

References 37 publications

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“…Genetic variation serves as an evolution driver, and is affected by selection pressure during plant evolution. Thus, CDS is under stronger selection pressure compared with UTR [ 18 ], and indels with sizes of multiples of three not resulting in frameshift mutation suffer less selection pressure [ 19 ], because indels are expected to be deleterious when they occur in functional sequences, especially coding regions where frameshift can be induced [ 20 ]. Here, the genetic variation frequencies were lower in CDS than in UTR, and 3n-indels had higher frequencies compared to non-3n indels with adjacent sizes in CDS but not in UTR (Fig.…”

Section: Discussionmentioning

confidence: 99%

The non-random patterns of genetic variation induced by asymmetric somatic hybridization in wheat

Wang

Feng

et al. 2018

BMC Plant Biol

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BackgroundAsymmetric somatic hybridization is an efficient crop breeding approach by introducing several exogenous chromatin fragments, which leads to genomic shock and therefore induces genome-wide genetic variation. However, the fundamental question concerning the genetic variation such as whether it occurs randomly and suffers from selection pressure remains unknown.ResultsHere, we explored this issue by comparing expressed sequence tags of a common wheat cultivar and its asymmetric somatic hybrid line. Both nucleotide substitutions and indels (insertions and deletions) had lower frequencies in coding sequences than in un-translated regions. The frequencies of nucleotide substitutions and indels were both comparable between chromosomes with and without introgressed fragments. Nucleotide substitutions distributed unevenly and were preferential to indel-flanking sequences, and the frequency of nucleotide substitutions at 5′-flanking sequences of indels was obviously higher in chromosomes with introgressed fragments than in those without exogenous fragment. Nucleotide substitutions and indels both had various frequencies among seven groups of allelic chromosomes, and the frequencies of nucleotide substitutions were strongly negatively correlative to those of indels. Among three sets of genomes, the frequencies of nucleotide substitutions and indels were both heterogeneous, and the frequencies of nucleotide substitutions exhibited drastically positive correlation to those of indels.ConclusionsOur work demonstrates that the genetic variation induced by asymmetric somatic hybridization is attributed to both whole genomic shock and local chromosomal shock, which is a predetermined and non-random genetic event being closely associated with selection pressure. Asymmetric somatic hybrids provide a worthwhile model to further investigate the nature of genomic shock induced genetic variation.Electronic supplementary materialThe online version of this article (10.1186/s12870-018-1474-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The non-random patterns of genetic variation induced by asymmetric somatic hybridization in wheat

Wang

Feng

et al. 2018

BMC Plant Biol

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“…5'UTRs contain at least two types of translational regulatory elements—uORFs and G4s. The presence or absence of these regulatory elements can be altered by AS or AP [ 29 , 73 , 74 , 75 ]. These two types of regulatory mechanisms may occur separately or concurrently [ 76 ].…”

Section: Alternative 5'utr and Translational Regulations In Cancermentioning

confidence: 99%

“…By definition, the AUG codon should be located in 5'UTR, but not necessarily in the first exon. The stop codon can be located either in 5'UTR or in CDS [ 74 ]. The sequence contexts of 5'UTRs can influence the efficiency of translational regulations of uORFs, including the length of 5'UTR, the number of uORFs in the 5'UTR, the Kozak sequence context of the uORF, and whether the uORF overlaps with the downstream main CDS [ 77 , 78 ].…”

Section: Alternative 5'utr and Translational Regulations In Cancermentioning

confidence: 99%

“…The sequence contexts of 5'UTRs can influence the efficiency of translational regulations of uORFs, including the length of 5'UTR, the number of uORFs in the 5'UTR, the Kozak sequence context of the uORF, and whether the uORF overlaps with the downstream main CDS [ 77 , 78 ]. uORFs may also induce NMD because these elements by definition include one stop codon, which is usually located upstream of the canonical stop codon [ 74 ]. uORFs occur in more than 40% of human transcripts [ 77 , 79 ], and are selectively constrained possibly because of their repressive nature [ 73 ].…”

Section: Alternative 5'utr and Translational Regulations In Cancermentioning

confidence: 99%

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Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis

Chen

2014

IJMS

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Alternative RNA structures (ARSs), or alternative transcript isoforms, are critical for regulating cellular phenotypes in humans. In addition to generating functionally diverse protein isoforms from a single gene, ARS can alter the sequence contents of 5'/3' untranslated regions (UTRs) and intronic regions, thus also affecting the regulatory effects of these regions. ARS may introduce premature stop codon(s) into a transcript, and render the transcript susceptible to nonsense-mediated decay, which in turn can influence the overall gene expression level. Meanwhile, ARS can regulate the presence/absence of upstream open reading frames and microRNA targeting sites in 5'UTRs and 3'UTRs, respectively, thus affecting translational efficiencies and protein expression levels. Furthermore, since ARS may alter exon-intron structures, it can influence the biogenesis of intronic microRNAs and indirectly affect the expression of the target genes of these microRNAs. The connections between ARS and multiple regulatory mechanisms underline the importance of ARS in determining cell fate. Accumulating evidence indicates that ARS-coupled regulations play important roles in tumorigenesis. Here I will review our current knowledge in this field, and discuss potential future directions.

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“…In the former case, AS may lead to significant changes in protein sequences or the initiation of nonsense-mediated decay [26,27], thus adding another layer of regulatory complexity. In the latter case, the altered UTR sequences may cause changes in transcriptional or translational regulations [28][29][30][31]. Fourthly, CSEs and ASEs are known to have significantly different evolutionary rates [25,32], and different paths of evolution [33].…”

Section: The Biological Significance Of Exon Classification In Alternmentioning

confidence: 99%

Are all of the human exons alternatively spliced?

Chen¹

2013

Briefings in Bioinformatics

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Alternative mRNA splicing (AS) is a major mechanism for increasing regulatory complexity. A key concept in AS is the distinction between alternatively and constitutively spliced exons (ASEs and CSEs, respectively). ASEs and CSEs have been reported to be differentially regulated, and to have distinct biological properties. However, the recent flood of RNA-sequencing data has obscured the boundary between ASEs and CSEs. Researchers are beginning to question whether ‘authentic CSEs’ do exist, and whether the ASE/CSE distinction is biologically invalid. Here, I examine the influences of increasing transcriptome data on the human ASE/CSE classification and our past understanding of the properties of these two types of exons. Interestingly, although the percentage of human ASEs has increased dramatically in recent years, the overall distinction between ASEs and CSEs remain valid. For example, CSEs are longer, evolve more slowly, and less frequently correspond to intrinsically disordered protein regions than ASEs. In addition, only a relatively small number of human genes have their transcripts composed entirely of ASEs despite the large amount of high-throughput transcriptome information. Therefore, the ‘backbone’ concept of AS, in which CSEs constitute the invariant part and ASEs the flexible part of the transcript, appears to be generally true despite the increasing percentage of ASEs in the human exome.

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Exploring the selective constraint on the sizes of insertions and deletions in 5' untranslated regions in mammals

Cited by 11 publications

References 37 publications

The non-random patterns of genetic variation induced by asymmetric somatic hybridization in wheat

The non-random patterns of genetic variation induced by asymmetric somatic hybridization in wheat

Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis

Are all of the human exons alternatively spliced?

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