Roy Scott W
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
BMC Evol Biol. 2009 Aug 7;9:192. doi: 10.1186/1471-2148-9-192.
Eukaryotic pre-mRNA gene transcripts are processed by the spliceosome to remove portions of the transcript, called spliceosomal introns. The spliceosome recognizes intron boundaries by the presence of sequence signals (motifs) contained in the actual transcript, thus sequence changes in the genome that affect existing splicing signals or create new signals may lead to changes in transcript splicing patterns. Such changes may lead to previously excluded (intronic) transcript regions being included (exonic) or vice versa. Such changes can affect the encoded protein sequence and/or post-transcriptional regulation, and are thus a potentially important source of genomic and phenotypic novelty. Two recent papers suggest that such changes may be a major force in remodeling of eukaryotic gene structures, however the rate of occurrence of such changes has not been assessed at the genomic level.
I studied four closely related species of Cryptoccocus fungi. Among 28,256 studied introns, canonical GT/C...AG boundaries are nearly universally conserved across all four species. Among only 40 observed cases of cDNA-confirmed non-conserved intron boundaries, most are likely to involve alternative splicing. I find only five cases of "intronization," intron creation from an internal exonic region by de novo emergence of new splicing boundaries, and no cases of the reverse process, "de-intronization." I find no more than ten clear cases of true movement of an intron boundary of a possibly constitutively spliced intron, and no clear cases of true "intron sliding," in which changes in the positions of both intron boundaries could lead to a movement of the intron position along the coding sequence.
These results suggest that intronization, de-intronization, and intron boundary movement are rare events in evolution.
真核生物前体mRNA基因转录本由剪接体进行加工，以去除转录本的某些部分，即剪接体内含子。剪接体通过实际转录本中所含的序列信号（基序）识别内含子边界，因此基因组中的序列变化若影响现有剪接信号或产生新信号，可能会导致转录本剪接模式发生改变。此类变化可能会使先前被排除的（内含子）转录区域被纳入（外显子），反之亦然。这种变化会影响编码的蛋白质序列和/或转录后调控，因此是基因组和表型新奇性的潜在重要来源。最近的两篇论文表明，此类变化可能是真核基因结构重塑的主要力量，然而，此类变化在基因组水平上的发生率尚未得到评估。
我研究了四种密切相关的隐球菌属真菌。在研究的28256个内含子中，标准的GT/C...AG边界在所有四个物种中几乎普遍保守。在仅40例经cDNA确认的非保守内含子边界病例中，大多数可能涉及可变剪接。我仅发现5例“内含子化”情况，即通过新出现的剪接边界从内部外显子区域产生内含子，未发现反向过程“去内含子化”的情况。我发现可能组成型剪接的内含子边界真正移动的明确病例不超过10例，也没有明确病例显示真正的“内含子滑动”，即内含子边界位置的变化会导致内含子位置沿编码序列移动。
这些结果表明，内含子化、去内含子化和内含子边界移动在进化中是罕见事件。
