Tarrío Rosa, Ayala Francisco J, Rodríguez-Trelles Francisco
Grupo de Medicina Xenómica-Centro de Investigación Biomédica en Red de Enfermedades Raras, Hospital Clínico Universitario, Universidade de Santiago de Compostela, 15706 Santiago, Spain.
Proc Natl Acad Sci U S A. 2008 May 20;105(20):7223-8. doi: 10.1073/pnas.0802941105. Epub 2008 May 7.
Spliceosomal introns, a hallmark of eukaryotic gene organization, were an unexpected discovery. After three decades, crucial issues such as when and how introns first appeared in evolution remain unsettled. An issue yet to be answered is how intron positions arise de novo. Phylogenetic investigations concur that intron positions continue to emerge, at least in some lineages. Yet genomic scans for the sources of introns occupying new positions have been fruitless. Two alternative solutions to this paradox are: (i) formation of new intron positions halted before the recent past and (ii) it continues to occur, but through processes different from those generally assumed. One process generally dismissed is intron sliding--the relocation of a preexisting intron over short distances--because of supposed associated deleterious effects. The puzzle of intron gain arises owing to a pervasive operational definition of introns, which sees them as precisely demarcated segments of the genome separated from the neighboring nonintronic DNA by unmovable limits. Intron homology is defined as position homology. Recent studies of pre-mRNA processing indicate that this assumption needs to be revised. We incorporate recent advances on the evolutionarily frequent process of alternative splicing, by which exons of primary transcripts are spliced in different patterns, into a new model of intron sliding that accounts for the diversity of intron positions. We posit that intron positional diversity is driven by two overlapping processes: (i) background process of continuous relocation of preexisting introns by sliding and (ii) spurts of extensive gain/loss of new intron sequences.
剪接体内含子是真核基因组织的一个标志，是一项意外发现。三十年后，诸如内含子在进化中何时以及如何首次出现等关键问题仍未解决。一个有待回答的问题是内含子位置如何从头产生。系统发育研究一致认为，至少在某些谱系中，内含子位置仍在不断出现。然而，对占据新位置的内含子来源进行的基因组扫描却毫无结果。针对这一矛盾有两种替代解决方案：（i）新内含子位置的形成在近代之前就已停止；（ii）它仍在继续发生，但通过与通常假设的过程不同的过程。一个通常被摒弃的过程是内含子滑动——即一个预先存在的内含子在短距离内重新定位——因为假定其存在相关的有害影响。内含子获得之谜源于对内含子的一种普遍操作定义，该定义将它们视为基因组中精确划分的片段，与相邻的非内含子DNA由不可移动的界限分隔开来。内含子同源性被定义为位置同源性。最近对前体mRNA加工的研究表明，这一假设需要修正。我们将最近关于可变剪接这一在进化中频繁发生的过程（通过该过程，初级转录本的外显子以不同模式进行剪接）的进展纳入一个新的内含子滑动模型，该模型解释了内含子位置的多样性。我们假定内含子位置多样性由两个重叠的过程驱动：（i）通过滑动使预先存在的内含子持续重新定位的背景过程；（ii）新内含子序列大量获得/丢失的突发情况。
