Koonin Eugene V, Makarova Kira S, Rogozin Igor B, Davidovic Laetitia, Letellier Marie-Claude, Pellegrini Luca
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Genome Biol. 2003;4(3):R19. doi: 10.1186/gb-2003-4-3-r19. Epub 2003 Feb 28.
The rhomboid family of polytopic membrane proteins shows a level of evolutionary conservation unique among membrane proteins. They are present in nearly all the sequenced genomes of archaea, bacteria and eukaryotes, with the exception of several species with small genomes. On the basis of experimental studies with the developmental regulator rhomboid from Drosophila and the AarA protein from the bacterium Providencia stuartii, the rhomboids are thought to be intramembrane serine proteases whose signaling function is conserved in eukaryotes and prokaryotes.
Phylogenetic tree analysis carried out using several independent methods for tree constructions and the corresponding statistical tests suggests that, despite its broad distribution in all three superkingdoms, the rhomboid family was not present in the last universal common ancestor of extant life forms. Instead, we propose that rhomboids evolved in bacteria and have been acquired by archaea and eukaryotes through several independent horizontal gene transfers. In eukaryotes, two distinct, ancient acquisitions apparently gave rise to the two major subfamilies, typified by rhomboid and PARL (presenilins-associated rhomboid-like protein), respectively. Subsequent evolution of the rhomboid family in eukaryotes proceeded by multiple duplications and functional diversification through the addition of extra transmembrane helices and other domains in different orientations relative to the conserved core that harbors the protease activity.
Although the near-universal presence of the rhomboid family in bacteria, archaea and eukaryotes appears to suggest that this protein is part of the heritage of the last universal common ancestor, phylogenetic tree analysis indicates a likely bacterial origin with subsequent dissemination by horizontal gene transfer. This emphasizes the importance of explicit phylogenetic analysis for the reconstruction of ancestral life forms. A hypothetical scenario for the origin of intracellular membrane proteases from membrane transporters is proposed.
多跨膜蛋白的菱形蛋白家族在膜蛋白中展现出独特的进化保守水平。除了几个基因组较小的物种外，它们几乎存在于古菌、细菌和真核生物的所有已测序基因组中。基于对果蝇发育调节因子菱形蛋白和斯氏普罗威登斯菌的AarA蛋白的实验研究，菱形蛋白被认为是膜内丝氨酸蛋白酶，其信号传导功能在真核生物和原核生物中保守。
使用几种独立的建树方法及相应统计检验进行的系统发育树分析表明，尽管菱形蛋白家族在所有三个超界中广泛分布，但在现存生命形式的最后一个普遍共同祖先中并不存在。相反，我们提出菱形蛋白在细菌中进化，并通过几次独立的水平基因转移被古菌和真核生物获得。在真核生物中，两次不同的古老获得事件显然分别产生了两个主要亚家族，分别以菱形蛋白和PARL（早老素相关菱形样蛋白）为代表。真核生物中菱形蛋白家族的后续进化通过多次复制和功能多样化进行，即通过在相对于具有蛋白酶活性的保守核心以不同方向添加额外的跨膜螺旋和其他结构域。
尽管菱形蛋白家族在细菌、古菌和真核生物中几乎普遍存在，这似乎表明该蛋白是最后一个普遍共同祖先遗产的一部分，但系统发育树分析表明其可能起源于细菌，随后通过水平基因转移传播。这强调了明确的系统发育分析对于重建祖先生命形式的重要性。提出了一个从膜转运蛋白起源细胞内膜蛋白酶的假设情景。
