Lamb David C, Goldstone Jared V, Belhaouari Djamal Brahim, Andréani Julien, Farooqi Ayesha, Allen Michael J, Kelly Steven L, La Scola Bernard, Stegeman John J
Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, Wales SA2 8PP, UK.
Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02543, USA.
Res Sq. 2024 Oct 25:rs.3.rs-5246363. doi: 10.21203/rs.3.rs-5246363/v1.
Cytochrome b5 is a small electron transport protein that is found in animals, plants, fungi and photosynthetic proteobacteria where it plays key metabolic roles in energy production, lipid and sterol biosynthesis and cytochrome P450 biochemistry. Previously it was shown that a gene encoding a soluble and functional cytochrome b5 protein was encoded in the large double stranded DNA virus OtV2 that infects the unicellular marine green alga , the smallest free-living eukaryote described to-date. This single gene represented a unique finding in the virosphere. We now report that genes for soluble and membrane-bound cytochromes b5 also occur in giant viruses in the proposed order Megavirales, particularly the AT-rich and . Conversely, other members of the taxa such as the GC-rich have not been found to encode cytochrome b5 as yet. Megaviruses encoding cytochrome b5 have been isolated from the deep ocean, from freshwater and terrestrial sources, as well as from human patients. Giant virus cytochrome b5 proteins share high sequence identity with one another (45-95% depending on group) but no more than 25% identity with the cytochrome b5 gene product we identified in , an amoeba host for many giant viruses. Thus, the origin of the unique cytochrome b5 genes in giant viruses remains unknown. Examination of viral cytochrome b5 primary amino acid sequences revealed that some have either a N- or C-terminal transmembrane anchor, whilst others lack a membrane anchor and are thus predicted to be soluble proteins. This cytochrome b5 topography suggests adapted biochemical functions in those viruses. Our findings raise questions regarding the evolution and diversity of cytochrome b5 proteins in nature, adding to questions about the origin of viral haemoproteins in general.
细胞色素b5是一种小型电子传递蛋白，存在于动物、植物、真菌和光合蛋白细菌中，在能量产生、脂质和甾醇生物合成以及细胞色素P450生物化学过程中发挥关键的代谢作用。此前研究表明，在感染单细胞海洋绿藻（迄今描述的最小自由生活真核生物）的大型双链DNA病毒OtV2中编码了一种可溶性且具有功能的细胞色素b5蛋白基因。这个单一基因在病毒圈中代表了一个独特的发现。我们现在报告，可溶性和膜结合细胞色素b5的基因也存在于拟菌病毒目（Megavirales）的巨型病毒中，特别是富含AT的病毒和 。相反，该分类群的其他成员，如富含GC的 ，尚未发现编码细胞色素b5。编码细胞色素b5的巨型病毒已从深海、淡水和陆地来源以及人类患者中分离出来。巨型病毒细胞色素b5蛋白彼此之间具有高度的序列同一性（根据组别不同，同一性为45 - 95%），但与我们在许多巨型病毒的变形虫宿主 中鉴定的细胞色素b5基因产物的同一性不超过25%。因此，巨型病毒中独特的细胞色素b5基因的起源仍然未知。对病毒细胞色素b5一级氨基酸序列的研究表明，一些序列具有N端或C端跨膜锚定，而其他序列则缺乏膜锚定，因此预计是可溶性蛋白。这种细胞色素b5的拓扑结构表明这些病毒具有适应性的生化功能。我们的发现引发了关于自然界中细胞色素b5蛋白的进化和多样性的问题，也增加了关于病毒血红蛋白起源的普遍问题。
