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【期刊论文】Selection for the miniaturization of highly expressed genes
牛登科, Shu-Wei Li, Liang Feng, Deng-Ke Niu *
Biochemical and Biophysical Research Communications 360(2007)586-592,-0001,():
-1年11月30日
Most widely expressed genes are also highly expressed. Based on high or wide expression, different models were proposed to explain the small sizes of highly/widely expressed genes. We found that housekeeping genes are not more compact than narrowly expressed genes with similar expression levels, but compactness and expression level are correlated in housekeeping genes (except that highly expressed Arabidopsis HK genes have longer intron length). Meanwhile, we found evidence that genes with high functional/regulatory complexity do not have longer introns and longer proteins. The genome design hypothesis is thus not supported. Furthermore, we found that housekeeping genes are not more compact than the narrowly expressed somatic genes with similar average expression levels. Because housekeeping genes are expected to have much higher germline expression levels than narrowly expressed somatic genes, transcriptionassociated deletion bias is not supported. Selection of the compactness of highly expressed genes for economy is supported.
Intron length, Protein length, Intron number, Protein domain number, Energetic cost, Gene expression
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【期刊论文】Protecting exons from deleterious R-loops: a potential advantage of having introns
牛登科, Deng-Ke Niu*
,-0001,():
-1年11月30日
Background: Accumulating evidence indicates that the nascent RNA can invade and pair with one strand of DNA, forming an R-loop structure that threatens the stability of the genome. In addition, the cost and benefit of introns are still in debate. Results: At least three factors are likely required for the R-loop formation: 1) sequence complementarity between the nascent RNA and the target DNA, 2) spatial juxtaposition between the nascent RNA and the template DNA, and 3) accessibility of the template DNA and the nascent RNA. The removal of introns from pre-mRNA reduces the complementarity between RNA and the template DNA and avoids the spatial juxtaposition between the nascent RNA and the template DNA. In addition, the secondary structures of group I and group II introns may act as spatial obstacles for the formation of R-loops between nearby exons and the genomic DNA. Conclusion: Organisms may benefit from introns by avoiding deleterious R-loops. The potential contribution of this benefit in driving intron evolution is discussed. I propose that additional RNA polymerases may inhibit R-loop formation between preceding nascent RNA and the template DNA. This idea leads to a testable prediction: intermittently transcribed genes and genes with frequently prolonged transcription should have higher intron density. Reviewers: This article was reviewed by Dr. Eugene V. Koonin, Dr. Alexei Fedorov (nominated by Dr. Laura F Landweber), and Dr. Scott W. Roy (nominated by Dr. Arcady Mushegian).
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【期刊论文】mRNA-Mediated Intron Losses: Evidence from Extraordinarily Large Exons
牛登科, Deng-Ke Niu, Wen-Ru Hou, and Shu-Wei Li
,-0001,():
-1年11月30日
Multicellular eukaryotes that have high intron density have their introns almost evenly distributed within genes, but unicellular eukaryotes that are generally intron poor have their introns asymmetrically distributed toward the 5# ends of genes. This was explained by homologous recombination of genomic DNA with the cDNA reverse transcribed from the 3# polyadenylated tail of spliced mRNA. This paper is to study whether mRNA-mediated intron losses have ever occurred in multicellular eukaryotes. If intron losses were mRNA-mediated, adjacent introns should be commonly lost together. A direct result is fusion of several previously adjacent exons and producing a large exon. We found that extraordinarily large exons (ELEs) are common not only in unicellular eukaryotes but also in multicellular eukaryotes. The percentage of genes having ELEs is negatively correlated with intron abundance. In addition, the number of lost introns estimated from the relative lengths of ELEs is negatively correlated with the number of extant introns. These results support mRNA-mediated intron losses in all eukaryotes. Moreover, we found that the ELEs of intron-common eukaryotes (with more than 0.5 intron per gene on average) are not only located at 3# ends but also at 5# ends and the middle of genes. This is contrary to what would be expected if the involved cDNAs were reverse transcribed from the 3# polyadenosine ends. A remarkable difference in intron distribution was revealed between intron-rare eukaryotes and intron-common eukaryotes. The intron-rare eukaryotes show very strong 5#-biased intron distribution, whereas the intron-common eukaryotes display even intron distribution or only weak 5#-biased distribution. We suspected that intron losses from 3# end of genes may be limited in intron-rare eukaryotes. The intron losses from intron-common eukaryotes should have other priming mechanism, like self-primed reverse transcription.
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【期刊论文】Evidence against the energetic cost hypothesis for the short intronsin highly expressed genes
牛登科, Yi-Fei Huang and Deng-Ke Niu*
,-0001,():
-1年11月30日
Background: In animals, the moss Physcomitrella patens and the pollen of Arabidopsis thaliana, highlyexpressed genes have shorter introns than weakly expressed genes. A popular explanation for thisis selection for transcription efficiency, which includes two sub-hypotheses: to minimize theenergetic cost or to minimize the time cost.Results: In an individual human, different organs may differ up to hundreds of times in cell number(for example, a liver versus a hypothalamus). Considered at the individual level, a gene specificallyexpressed in a large organ is actually transcribed tens or hundreds of times more than a gene witha similar expression level (a measure of mRNA abundance per cell) specifically expressed in a smallorgan. According to the energetic cost hypothesis, the former should have shorter introns than thelatter. However, in humans and mice we have not found significant differences in intron lengthbetween large-tissue/organ-specific genes and small-tissue/organ-specific genes with similarexpression levels. Qualitative estimation shows that the deleterious effect (that is, the energeticburden) of long introns in highly expressed genes is too negligible to be efficiently selected againstin mammals. Conclusion: The short introns in highly expressed genes should not be attributed to energyconstraint. We evaluated evidence for the time cost hypothesis and other alternatives.
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