Massive expansions of Dscam splicing diversity via staggered homologous recombination during arthropod evolution
Massive expansions of Dscam splicing diversity via staggered homologous recombination during arthropod evolution
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DOI：
10.1261/rna.1812710
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发表时间：
2010-01-01
期刊：
影响因子：
4.5
通讯作者：
Graveley, Brenton R.
中科院分区：
文献类型：
--
作者：
Lee, Christopher;Kim, Namshin;Graveley, Brenton R.
节肢动物唐氏综合征细胞粘附分子（Dscam）基因可以通过大量编码免疫球蛋白可变结构域的外显子的组合剪接产生数以万计的蛋白质异构体，这些外显子被组织成三簇，即外显子4,6和9簇。蛋白质多样性对神经系统发育和免疫功能至关重要。我们对20种节肢动物（每种节肢动物含有46 - 96个外显子）的Dscam进行了广泛的系统发育分析，以重建外显子复制和丢失事件的详细历史，这些外显子复制和丢失事件在4.5亿年的进化中构建了这个非凡的系统。虽然外显子4簇的结构是古老的，但外显子6和9簇在每个昆虫谱系中都经历了大量独立的扩展。通过对近2000个重复外显子的分析，可以详细地重建这些重复事件的时间、位置和边界。这些数据清楚地表明，新的Dscam外显子在节肢动物进化过程中不断出现，并且这一过程仍然发生在外显子6和9集群中。最近重复的区域显示对应于单个外显子和相邻的内含子的边界。这些重复事件的边界、同源性、位置、聚类和相对频率强烈表明，交错同源重组是新Dscam外显子进化的主要机制。这些数据提供了复杂基因结构如何进化的非常详细的图像，并揭示了这一过程背后的分子机制。
The arthropod Down syndrome cell adhesion molecule (Dscam) gene can generate tens of thousands of protein isoforms via combinatorial splicing of numerous alternative exons encoding immunoglobulin variable domains organized into three clusters referred to as the exon 4, 6, and 9 clusters. Dscam protein diversity is important for nervous system development and immune functions. We have performed extensive phylogenetic analyses of Dscam from 20 arthropods ( each containing between 46 and 96 alternative exons) to reconstruct the detailed history of exon duplication and loss events that built this remarkable system over 450 million years of evolution. Whereas the structure of the exon 4 cluster is ancient, the exon 6 and 9 clusters have undergone massive, independent expansions in each insect lineage. An analysis of nearly 2000 duplicated exons enabled detailed reconstruction of the timing, location, and boundaries of these duplication events. These data clearly show that new Dscam exons have arisen continuously throughout arthropod evolution and that this process is still occurring in the exon 6 and 9 clusters. Recently duplicated regions display boundaries corresponding to a single exon and the adjacent intron. The boundaries, homology, location, clustering, and relative frequencies of these duplication events strongly suggest that staggered homologous recombination is the major mechanism by which new Dscam exons evolve. These data provide a remarkably detailed picture of how complex gene structure evolves and reveal the molecular mechanism behind this process.