A minimal gene set for cellular life derived by comparison of complete bacterial genomes
A minimal gene set for cellular life derived by comparison of complete bacterial genomes
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DOI：
10.1073/pnas.93.19.10268
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发表时间：
1996-09-17
影响因子：
11.1
通讯作者：
Koonin, EV
中科院分区：
文献类型：
--
作者：
Mushegian, AR;Koonin, EV
最近测序的寄生细菌生殖支原体（Mycoplasma genitalium）的基因组仅包含468个已鉴定的蛋白质编码基因，其被称为最小基因互补（minimum gene complement）[Fraser，C. M.，Gocayne，J.D.，白色，O.，亚当斯，M. D、克莱顿河一、等人（1995）Science 270，397-403]。虽然M.生殖器基因组确实是已知细胞生命形式中最小的，没有证据表明它是最小的自给自足基因组，为了得到这样的基因组，我们比较了468个预测的M。生殖器蛋白质序列与由另一个完全测序的小细菌基因组编码的1703个蛋白质序列，即流感嗜血杆菌。M.生殖器和H.流感属于两种古老的细菌谱系，即，分别为革兰氏阳性菌和革兰氏阴性菌。因此，在这两种细菌中保守的基因几乎肯定是细胞功能所必需的。正是这类基因最有可能接近最小基因集。我们发现，240米。生殖器基因与H.流感。这种基因的集合福尔斯不足以构成最小集合，因为缺少了一些负责基本途径中中间步骤的酶。其明显的原因是，当两种生物体中的非正交蛋白质实现相同的功能时，我们称之为非正交基因置换的现象。我们鉴定了22个非直向置换，并用相应的M补充了直向同源物的集合。生殖器基因在检查所得的262个基因的列表中可能的功能冗余和明显的寄生虫特异性基因的存在后，去除了6个基因。我们认为，剩下的256个基因接近维持现代细胞存在所必需的最小基因集。大多数由最小集合的基因编码的蛋白质具有真核或古细菌同源物，但DNA复制的七个关键蛋白质没有。我们推测，三个主要王国的最后一个共同祖先具有RNA基因组。探索可能性以进一步减少最小集合来模拟可能存在于生命进化的非常早期阶段的原始细胞。
The recently sequenced genome of the parasitic bacterium Mycoplasma genitalium contains only 468 identified protein-coding genes that have been dubbed a minimal gene complement [Fraser, C. M., Gocayne, J. D., White, O., Adams, M. D., Clayton, R. A., et al. (1995) Science 270, 397-403]. Although the M. genitalium gene complement is indeed the smallest among known cellular life forms, there is no evidence that it is the minimal self-sufficient gene set, To derive such a set, we compared the 468 predicted M. genitalium protein sequences with the 1703 protein sequences encoded by the other completely sequenced small bacterial genome, that of Haemophilus influenzae. M. genitalium and H. influenzae belong to two ancient bacterial lineages, i.e., Gram-positive and Gram-negative bacteria, respectively. Therefore, the genes that are conserved in these two bacteria are almost certainly essential for cellular function. It is this category of genes that is most likely to approximate the minimal gene set. We found that 240 M. genitalium genes have orthologs among the genes of H. influenzae. This collection of genes falls short of comprising the minimal set as some enzymes responsible for intermediate steps in essential pathways are missing. The apparent reason for this is the phenomenon that we call nonorthologous gene displacement when the same function is fulfilled by nonorthologous proteins in two organisms. We identified 22 nonorthologous displacements and supplemented the set of orthologs with the respective M. genitalium genes. After examining the resulting List of 262 genes for possible functional redundancy and for the presence of apparently parasite-specific genes, 6 genes were removed. We suggest that the remaining 256 genes are close to the minimal gene set that is necessary and sufficient to sustain the existence of a modern-type cell. Most of the proteins encoded by the genes from the minimal set have eukaryotic or archaeal homologs but seven key proteins of DNA replication do not. We speculate that the last common ancestor of the three primary kingdoms had an RNA genome. Possibilities are explored to further reduce the minimal set to model a primitive cell that might have existed at a very early stage of life evolution.