School of Physics, Osnabrueck University, Osnabrueck, 49069, Germany.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.
Biochemistry (Mosc). 2020 Dec;85(12):1518-1542. doi: 10.1134/S0006297920120056.
In 1986, Vladimir Skulachev and his colleagues coined the term "Sodium World" for the group of diverse organisms with sodium (Na)-based bioenergetics. Albeit only few such organisms had been discovered by that time, the authors insightfully noted that "the great taxonomic variety of organisms employing the Na-cycle points to the ubiquitous distribution of this novel type of membrane-linked energy transductions". Here we used tools of bioinformatics to follow expansion of the Sodium World through the evolutionary time and taxonomic space. We searched for those membrane protein families in prokaryotic genomes that correlate with the use of the Na-potential for ATP synthesis by different organisms. In addition to the known Na-translocators, we found a plethora of uncharacterized protein families; most of them show no homology with studied proteins. In addition, we traced the presence of Na-based energetics in many novel archaeal and bacterial clades, which were recently identified by metagenomic techniques. The data obtained support the view that the Na-based energetics preceded the proton-dependent energetics in evolution and prevailed during the first two billion years of the Earth history before the oxygenation of atmosphere. Hence, the full capacity of Na-based energetics in prokaryotes remains largely unexplored. The Sodium World expanded owing to the acquisition of new functions by Na-translocating systems. Specifically, most classes of G-protein-coupled receptors (GPCRs), which are targeted by almost half of the known drugs, appear to evolve from the Na-translocating microbial rhodopsins. Thereby the GPCRs of class A, with 700 representatives in human genome, retained the Na-binding site in the center of the transmembrane heptahelical bundle together with the capacity of Na-translocation. Mathematical modeling showed that the class A GPCRs could use the energy of transmembrane Na-potential for increasing both their sensitivity and selectivity. Thus, GPCRs, the largest protein family coded by human genome, stem from the Sodium World, which encourages exploration of other Na-dependent enzymes of eukaryotes.
1986 年，弗拉基米尔·斯库拉切夫（Vladimir Skulachev）及其同事创造了“钠世界”一词，用于指代一组具有基于钠的生物能量学的不同生物体。尽管当时仅发现了少数此类生物体，但作者富有远见地指出，“利用 Na 循环的生物体具有广泛的分类多样性，这表明这种新型的膜连接能量转导在普遍存在”。在这里，我们使用生物信息学工具来追踪“钠世界”在进化时间和分类空间中的扩展。我们在原核基因组中搜索与不同生物体利用 Na 势能合成 ATP 相关的膜蛋白家族。除了已知的 Na 转运蛋白外，我们还发现了大量未被表征的蛋白家族；其中大多数与已研究的蛋白没有同源性。此外，我们还追踪到了许多最近通过宏基因组技术鉴定的新型古菌和细菌进化枝中存在基于 Na 的能量学。获得的数据支持这样的观点，即在进化过程中，基于 Na 的能量学先于质子依赖的能量学出现，并在地球历史的前 20 亿年大气氧合作用之前占据主导地位。因此，原核生物中基于 Na 的能量学的全部潜力在很大程度上仍未被探索。“钠世界”的扩展是由于 Na 转运系统获得了新的功能。具体来说，几乎一半已知药物的靶标——大多数 G 蛋白偶联受体（GPCR）类，似乎是从 Na 转运微生物视紫红质进化而来的。因此，A 类 GPCR 保留了位于跨膜七螺旋束中心的 Na 结合位点以及 Na 转运能力，而 A 类 GPCR 包含了人类基因组中 700 个代表。数学建模表明，A 类 GPCR 可以利用跨膜 Na 势能的能量来提高其敏感性和选择性。因此，GPCR 是人类基因组中最大的蛋白质家族，起源于“钠世界”，这鼓励探索真核生物中其他依赖 Na 的酶。
