Kumar S, Balczarek K A, Lai Z C
Department of Biology, Pennsylvania State University 16802, USA.
Genetics. 1996 Mar;142(3):965-72. doi: 10.1093/genetics/142.3.965.
Effective intercellular communication is an important feature in the development of multicellular organisms. Secreted hedgehog (hh) protein is essential for both long- and short-range cellular signaling required for body pattern formation in animals. In a molecular evolutionary study, we find that the vertebrate homologs of the Drosophila hh gene arose by two gene duplications: the first gave rise to Desert hh, whereas the second produced the Indian and Sonic hh genes. Both duplications occurred before the emergence of vertebrates and probably before the evolution of chordates. The amino-terminal fragment of the hh precursor, crucial in long- and short-range intercellular communication, evolves two to four times slower than the carboxyl-terminal fragment in both Drosophila hh and its vertebrate homologues, suggesting conservation of mechanism of hh action in animals. A majority of amino acid substitutions in the amino- and carboxyl-terminal fragments are conservative, but the carboxyl-terminal domain has undergone extensive insertion-deletion events while maintaining its autocleavage protease activity. Our results point to similarity of evolutionary constraints among sites of Drosophila and vertebrate hh homologs and suggest some future directions for understanding the role of hh genes in the evolution of developmental complexity in animals.
有效的细胞间通讯是多细胞生物发育过程中的一个重要特征。分泌型刺猬蛋白（hh）对于动物身体模式形成所需的长距离和短距离细胞信号传导都至关重要。在一项分子进化研究中，我们发现果蝇hh基因的脊椎动物同源物是通过两次基因复制产生的：第一次产生了沙漠刺猬蛋白（Desert hh），而第二次产生了印度刺猬蛋白（Indian hh）和声波刺猬蛋白（Sonic hh）基因。这两次复制都发生在脊椎动物出现之前，可能也在脊索动物进化之前。hh前体的氨基末端片段在长距离和短距离细胞间通讯中至关重要，在果蝇hh及其脊椎动物同源物中，其进化速度比羧基末端片段慢两到四倍，这表明动物中hh作用机制具有保守性。氨基末端和羧基末端片段中的大多数氨基酸替换都是保守的，但羧基末端结构域在保持其自切割蛋白酶活性的同时经历了广泛的插入-缺失事件。我们的结果表明果蝇和脊椎动物hh同源物位点之间进化限制的相似性，并为理解hh基因在动物发育复杂性进化中的作用提出了一些未来的研究方向。
