Institute of Bioinformatics, University of Muenster, Muenster, Germany.
BMC Evol Biol. 2010 Feb 17;10:47. doi: 10.1186/1471-2148-10-47.
Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly.
We have investigated the evolution of U12-type introns among eighteen metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss, and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any vertebrate species and only five show conversion between the U12 and the U2-type. Although there are only nineteen U12-type introns in Drosophila melanogaster, we found one case of U2 to U12-type conversion, apparently mediated by the activation of cryptic U12 splice sites early in the dipteran lineage. Overall, loss of U12-type introns is more common than conversion to U2-type and the U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype than among introns of the AT-AC subtype. We also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported.
Although complete loss of the U12-type spliceosome has occurred repeatedly, U12 introns are extremely stable in some taxa, including eutheria. Loss of U12 introns or the genes containing them is more common than conversion to the U2-type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.
许多真核生物有两种剪接体，用于从信使 RNA 前体中去除内含子。主要的（U2）剪接体处理绝大多数内含子，称为 U2 型内含子，而次要的（U12）剪接体去除一小部分（小于 0.5%）的内含子，称为 U12 型内含子。U12 型内含子具有不同的序列元件，通常与 U2 型内含子一起存在于基因中。U12 型内含子的系统发育分布表明，次要剪接途径在真核生物进化中出现得非常早，并已多次丢失。
我们通过分析直系同源的 U12 型内含子簇，研究了 18 种后生动物基因组中 U12 型内含子的进化。对获得、丢失和类型转换的研究表明，内含子类型在脊椎动物中非常保守。在 180 个内含子簇中，只有 8 个在任何脊椎动物物种中丢失内含子，只有 5 个在 U12 和 U2 型之间转换。尽管黑腹果蝇（Drosophila melanogaster）只有 19 个 U12 型内含子，但我们发现了一个 U2 到 U12 型转换的例子，显然是由早期在双翅目谱系中激活的隐藏 U12 剪接位点介导的。总体而言，U12 型内含子的丢失比转换为 U2 型更为常见，并且 GT-AG 亚型的内含子比 AT-AC 亚型的内含子更频繁地发生 U12 到 U2 的转换。我们还发现了支持具有非典型末端二核苷酸（CT-AC、GG-AG 和 GA-AG）的天然 U12 型内含子的证据，这些内含子以前没有报道过。
尽管 U12 型剪接体已多次完全丢失，但 U12 内含子在某些类群中非常稳定，包括真兽类。U12 内含子或包含它们的基因的丢失比转换为 U2 型更为常见。天然 U12 型内含子的 U12 型末端二核苷酸的简并性比以前认为的要高。
