Nonsense-mediated decay enables intron gain in Drosophila

Intron number varies considerably among genomes, but despite their fundamental importance, the mutational mechanisms and evolutionary processes underlying the expansion of intron number remain unknown. Here we show that Drosophila, in contrast to most eukaryotic lineages, is still undergoing a dramatic rate of intron gain. These novel introns carry significantly weaker splice sites that may impede their identification by the spliceosome. Novel introns are more likely to encode a premature termination codon (PTC), indicating that nonsense-mediated decay (NMD) functions as a backup for weak splicing of new introns. Our data suggest that new introns originate when genomic insertions with weak splice sites are hidden from selection by NMD. This mechanism reduces the sequence requirement imposed on novel introns and implies that the capacity of the spliceosome to recognize weak splice sites was a prerequisite for intron gain during eukaryotic evolution.

不同物种的基因组中，内含子的数量差异悬殊，但尽管内含子具有核心生物学重要性，驱动内含子数量扩张的突变机制与进化过程仍未被阐明。我们在此证实，与绝大多数真核生物谱系不同，果蝇（Drosophila）仍在以极高速率获得新内含子。这些新内含子所携带的剪接位点（splice sites）显著偏弱，可能会阻碍剪接体（spliceosome）对其识别。新内含子更易编码提前终止密码子（premature termination codon, PTC），这表明无义介导的mRNA降解（nonsense-mediated decay, NMD）可作为新内含子弱剪接的备份机制。我们的研究数据显示，当携带弱剪接位点的基因组插入序列被无义介导的mRNA降解屏蔽于选择压力之外时，新内含子便得以产生。该机制降低了新内含子所需满足的序列约束，并暗示在真核生物进化历程中，剪接体识别弱剪接位点的能力是内含子获得事件得以发生的先决条件。