Evolutionary forces shape the human RFPL1,2,3 genes toward a role in neocortex development
Evolutionary forces shape the human RFPL1,2,3 genes toward a role in neocortex development
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DOI：
10.1016/j.ajhg.2008.07.007
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发表时间：
2008-08-08
影响因子：
9.8
通讯作者：
Krause, Karl-Heinz
中科院分区：
文献类型：
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作者：
Bonnefont, Jerome;Nikolaev, Sergey I.;Krause, Karl-Heinz
在灵长类进化过程中，大脑新皮层的大小和组织发生了巨大的变化。这可能是由于复制事件后新基因的出现，基因表达的进化变化和/或蛋白质进化的加速。在这里，我们描述了人类Ret指蛋白样（hRFPL）1，2，3基因簇的22号染色体上，这是反式激活的促皮质激素转录因子Pax 6。在分化的人类胚胎干细胞和发育中的人类新皮质中，在神经发生开始时检测到高hRFPL 1、2、3转录水平，而独特的小鼠RFPL基因在肝脏中表达，但在神经组织中不表达。对RFPL基因家族进化历史的研究表明，RFPL 1，2，3基因的祖先是在Euarchonta-Glires分裂后出现的。随后的重复事件导致卡他鼻类中存在多个RFPL 1，2，3基因（类似于34 mya），导致类人猿谱系中基因拷贝数增加。在卡他鼻症中，RFPL 1，2，3表达谱在肝脏上向新皮质和小脑发散。重要的是，与小脑、黑猩猩和猕猴新皮质相比，人类皮质RFPL 1、2、3表达显著增加。还观察到RFPL-蛋白质进化的加速，RFPL 1、2、3簇中的正选择迹象和两个新功能化事件（在所有RFPL中获得特异性RFPL-定义基序和在卡他鼻RFPL 1、2、3中获得N-末端29个氨基酸序列）。因此，我们建议，最近出现的PFPL 1，2，3基因的倍增有助于灵长类动物新皮层的大小和/或组织的变化。
The size and organization of the brain neocortex has dramatically changed during primate evolution. This is probably due to the emergence of novel genes after duplication events, evolutionary changes in gene expression, and/or acceleration in protein evolution. Here, we describe a human Ret finger protein-like (hRFPL) 1,2,3 gene cluster on chromosome 22, which is transactivated by the corticogenic transcription factor Pax6. High hRFPL1,2,3 transcript levels were detected at the onset of neurogenesis in differentiating human embryonic stem cells and in the developing human neocortex, whereas the unique murine RFPL gene is expressed in liver but not in neural tissue. Study of the evolutionary history of the RFPL gene family revealed that the RFPL1,2,3 gene ancestor emerged after the Euarchonta-Glires split. Subsequent duplication events led to the presence of multiple RFPL1,2,3 genes in Catarrhini (similar to 34 mya) resulting in an increase in gene copy number in the hominoid lineage. In Catarrhini, RFPL1,2,3 expression profile diverged toward the neocortex and cerebellum over the liver. Importantly, humans showed a striking increase in cortical RFPL1,2,3 expression in comparison to their cerebellum, and to chimpanzee and macaque neocortex. Acceleration in RFPL-protein evolution was also observed with signs of positive selection in the RFPL1,2,3 cluster and two neofunctionalization events (acquisition of a specific RFPL-Defining Motif in all RFPLs and of a N-terminal 29 amino-acid sequence in catarrhinian RFPL1,2,3). Thus, we propose that the recent emergence and multiplication of the PFPL1,2,3 genes contribute to changes in primate neocortex size and/or organization.