Identification of essential amino acid changes in paired domain evolution using a novel combination of evolutionary analysis and in vitro and in vivo studies.
Identification of essential amino acid changes in paired domain evolution using a novel combination of evolutionary analysis and in vitro and in vivo studies.
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DOI：
10.1093/oxfordjournals.molbev.a004212
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发表时间：
2002-09
影响因子：
10.7
通讯作者：
Hongmin Sun;S. Merugu;X. Gu;Y. Kang;D. P. Dickinson;P. Callaerts;Wen-Hsiung Li
中科院分区：
文献类型：
--
作者：
Hongmin Sun;S. Merugu;X. Gu;Y. Kang;D. P. Dickinson;P. Callaerts;Wen-Hsiung Li
Pax基因是由一个编码128个氨基酸的DNA结合域的配对框来定义的。它们参与中枢神经系统的发育、器官发生和肿瘤发生。已知的Pax基因被分成两个超群中的五个群。通过一种新的进化分析、体外结合分析和体内功能分析相结合的方法，我们确定了决定两个超群以及超群I中Pax-2、5、8和Pax-6亚群不同DNA结合特性的关键残基。两个超群之间结合特性的差异主要是由于配对结构域20和121位氨基酸的变化造成的。虽然Pax-2、Pax-5、Pax-8和Pax-6基团的配对结构域相差19个氨基酸，但它们不同的DNA结合特性几乎完全由单个氨基酸的变化决定。因此，少量的氨基酸变化可以在很大程度上解释已知的配对结构域之间结合性质的差异。我们选择负责基因间功能差异的候选位点的方法也应该对其他基因家族的研究有用。
Pax genes are defined by the presence of a paired box that encodes a DNA-binding domain of 128 amino acids. They are involved in the development of the central nervous system, organogenesis, and oncogenesis. The known Pax genes are divided into five groups within two supergroups. By means of a novel combination of evolutionary analysis, in vitro binding assays and in vivo functional analyses, we have identified the key residues that determine the differing DNA-binding properties of the two supergroups and of the Pax-2, 5, 8 and Pax-6 subgroups within supergroup I. The differences in binding properties between the two supergroups are largely caused by amino acid changes at residues 20 and 121 of the paired domain. Although the paired domains of the Pax-2, 5, 8 and the Pax-6 group differ by >19 amino acids, their distinct DNA-binding properties are determined almost completely by a single amino acid change. Thus, a small number of amino acid changes can account in large part for the divergence in binding properties among the known paired domains. Our approach for selecting candidate sites responsible for the functional divergence between genes should also be useful for studying other gene families.