Niu Deng-Ke
Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, College of Life Sciences, Beijing Normal University, Beijing, PR China.
Biol Direct. 2008 Nov 13;3:46. doi: 10.1186/1745-6150-3-46.
Previous studies have indicated that the wide variation in intron density (the number of introns per gene) among different eukaryotes largely reflects varying degrees of intron loss during evolution. The most popular model, which suggests that organisms lose introns through a mechanism in which reverse-transcribed cDNA recombines with the genomic DNA, concerns only one mutational force.
Using exons as the units of splicing-site recognition, exon definition constrains the length of exons. An intron-loss event results in fusion of flanking exons and thus a larger exon. The large size of the newborn exon may cause splicing errors, i.e., exon skipping, if the splicing of pre-mRNAs is initiated by exon definition. By contrast, if the splicing of pre-mRNAs is initiated by intron definition, intron loss does not matter. Exon definition may thus be a selective force against intron loss. An organism with a high frequency of exon definition is expected to experience a low rate of intron loss throughout evolution and have a high density of spliceosomal introns.
The majority of spliceosomal introns in vertebrates may be maintained during evolution not because of potential functions, but because of their splicing mechanism (i.e., exon definition). Further research is required to determine whether exon definition is a negative force in maintaining the high intron density of vertebrates.
This article was reviewed by Dr. Scott W. Roy (nominated by Dr. John Logsdon), Dr.Eugene V. Koonin, and Dr. Igor B. Rogozin (nominated by Dr. Mikhail Gelfand). For the full reviews,please go to the Reviewers' comments section.
先前的研究表明,不同真核生物的内含子密度(每个基因的内含子数量)差异很大,这在很大程度上反映了进化过程中内含子丢失的不同程度。最流行的模型认为,生物体通过逆转录的cDNA与基因组DNA重组的机制丢失内含子,该模型只涉及一种突变力量。
以外显子作为剪接位点识别的单位,外显子定义限制了外显子的长度。内含子丢失事件会导致侧翼外显子融合,从而形成更大的外显子。如果前体mRNA的剪接由外显子定义启动,那么新生外显子的大尺寸可能会导致剪接错误,即外显子跳跃。相比之下,如果前体mRNA的剪接由内含子定义启动,内含子丢失则无关紧要。因此,外显子定义可能是一种阻止内含子丢失的选择力量。预计在整个进化过程中,外显子定义频率高的生物体的内含子丢失率较低,并且剪接体内含子密度较高。
脊椎动物中的大多数剪接体内含子在进化过程中得以保留,可能不是因为其潜在功能,而是因为它们的剪接机制(即外显子定义)。需要进一步研究以确定外显子定义是否是维持脊椎动物高内含子密度的负面力量。
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