Evans D L, Mansel R E
Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.
J Mol Evol. 1995 Dec;41(6):775-83. doi: 10.1007/BF00173157.
The nature of the bcl-2 family of proto-oncogenes was analyzed by sequence alignment, secondary structure prediction, and phylogenetic techniques. Phylogenies were inferred from both the nucleic acid and amino acid sequences of the human, murine, rat, and chicken sequences for BCL-2 and BCL-X, human MCL1, murine A1, the nematode Caenorhabditis elegans and Caenorhabditis briggsiae ced-9 proteins, and the sequences BHRF1 from Epstein-Barr and LMW5-HL from African swine fever viruses. Both sequence alignment and secondary structure prediction techniques supported the conservation of both the overall secondary structure and the carboxy-terminal transmembrane domain in all members of the family. All the treeing methods employed (distance matrix, maximum likelihood, and parsimony) supported a tree in which the proapoptotic proteins BCL-2 and BCL-X represent the most recent additions to the group. All the trees also indicated that the viral proteins BHRF1 and LMW-HL arose from a common ancestor, an ancestor they shared in common with the pro-apoptotic control protein BAX, indicating that this function of BAX evolved only recently. The most ancient branches are represented by the nematode ced-9 protein and by the control genes MCL1 and A1, which in the treeing methods employed represent separate lineages within the most ancient grouping. These results demonstrate the evolution of a highly conserved family of developmental control genes from nematode to man--genes that encode proteins essential for normal development but which are highly conserved in terms of predicted structure and possible cellular localization. The evolutionary analysis also indicates that the family may be even larger than originally predicted and that other members are waiting to be discovered.
通过序列比对、二级结构预测和系统发育技术分析了原癌基因bcl-2家族的性质。从人、小鼠、大鼠和鸡的BCL-2和BCL-X、人MCL1、小鼠A1、线虫秀丽隐杆线虫和briggsiae ced-9蛋白的核酸和氨基酸序列，以及来自Epstein-Barr病毒的BHRF1序列和来自非洲猪瘟病毒的LMW5-HL序列推断系统发育。序列比对和二级结构预测技术均支持该家族所有成员的整体二级结构和羧基末端跨膜结构域的保守性。所采用的所有建树方法（距离矩阵法、最大似然法和简约法）均支持一种树状结构，其中促凋亡蛋白BCL-2和BCL-X是该组中最新添加的成员。所有的树状图还表明，病毒蛋白BHRF1和LMW-HL起源于一个共同祖先，它们与促凋亡调控蛋白BAX共有这个祖先，这表明BAX的这种功能是最近才进化出来的。最古老的分支由线虫ced-9蛋白以及调控基因MCL1和A1代表，在所采用的建树方法中，它们在最古老的分组中代表不同的谱系。这些结果证明了一个从线虫到人类的高度保守的发育调控基因家族的进化——这些基因编码正常发育所必需的蛋白质，但在预测结构和可能的细胞定位方面高度保守。进化分析还表明，该家族可能比最初预测的还要大，还有其他成员有待发现。
