Artificial cell manages a few rounds of cell division
Artificial cell manages a few rounds of cell division
人造细胞成功实现几轮细胞分裂
Understanding the origin of life requires addressing a collection of overlapping scientific questions. We’ve made a lot of progress toward explaining how simple chemicals present on an early Earth built the complex molecules used by life and how some of those chemicals built the first genetic/catalytic molecules. But we’re much further from understanding a key conundrum: How did membranes end up surrounding the first cells? 理解生命的起源需要解决一系列相互重叠的科学问题。我们已经在解释早期地球上的简单化学物质如何构建生命所需的复杂分子，以及其中一些化学物质如何构建出最初的遗传/催化分子方面取得了很大进展。但我们距离理解一个关键难题还很遥远：膜是如何最终包裹住最初的细胞的？
It’s relatively easy to make membranes spontaneously form in water, and they’ll enclose anything dissolved in that water, including nucleic acids. But the membranes then cut their interior off from everything else in the solution. Any interesting chemical reactions enclosed there would eat through the raw materials and grind to a halt. 在水中让膜自发形成相对容易，它们会包裹住水中溶解的任何物质，包括核酸。但随后，这些膜会将内部与溶液中的其他一切隔绝开来。任何被包裹在其中的有趣化学反应都会消耗掉原材料，最终陷入停滞。
Now, a lab at the University of Minnesota has announced that it has developed a simplified system in which a membrane encloses some genetic material but can continually import new materials supplied to it. The system also spontaneously divides, producing a few generations of “offspring” before things start failing. It’s still extremely dependent upon human intervention, but it might provide a new avenue to explore questions about the origin of life and what a truly minimalistic form of life might look like. 现在，明尼苏达大学的一个实验室宣布，他们开发出了一种简化系统，其中的膜包裹着一些遗传物质，但能够持续导入外部供应的新材料。该系统还能自发分裂，产生几代“后代”，之后才会开始失效。虽然它仍然极度依赖人工干预，但这可能为探索生命起源问题以及真正的极简生命形式提供了一条新途径。
The genetics of SpudCells
“土豆细胞”（SpudCells）的遗传学
The work was done by a team led by Kate Adamala, and it hasn’t yet undergone peer review (a draft manuscript has been posted online). It mostly involved putting together pieces of biological systems described or developed by other researchers and wrapping them in a membrane. Many of these pieces originated in viruses, which are often notable for having stripped-down versions of systems that are far more elaborate in cells. 这项工作由 Kate Adamala 领导的团队完成，目前尚未经过同行评审（草稿已在线发布）。它主要涉及将其他研究人员描述或开发出的生物系统片段组合在一起，并用膜将它们包裹起来。其中许多片段源自病毒，病毒通常以拥有细胞中更为复杂的系统的精简版本而著称。
For example, the system used to copy the DNA of what Adamala is calling a “SpudCell” is derived from a virus that infects bacteria called Phi29. A different research group had already demonstrated that DNA encoding the proteins this virus uses to copy its DNA can be placed inside a membrane, where it would replicate its own DNA. So the researchers adapted this to their own system, which spreads roughly 90,000 bases of DNA across seven separate circular DNA molecules. 例如，Adamala 称之为“SpudCell”（土豆细胞）的 DNA 复制系统源自一种感染细菌的 Phi29 病毒。另一个研究小组此前已经证明，将编码该病毒用于复制 DNA 的蛋白质的 DNA 放入膜内，它就能复制自身的 DNA。因此，研究人员将其适配到自己的系统中，该系统将大约 90,000 个 DNA 碱基分布在七个独立的环状 DNA 分子中。
One limitation of the SpudCell is that it has no way to ensure that, when the cells divide, each offspring receives copies of all seven of these molecules. Instead, the system simply makes a bunch of copies to increase the probability that some of them will end up in each of the offspring. It doesn’t entirely work; after five generations of divisions, the majority of the SpudCells are missing at least one of the seven molecules of its genome. SpudCell 的一个局限性在于，它无法确保细胞分裂时，每个后代都能获得所有七个分子的拷贝。相反，该系统只是制造大量拷贝，以增加每个后代都能获得其中一些分子的概率。但这并不完全奏效；经过五代分裂后，大多数 SpudCell 都会丢失其基因组中七个分子中的至少一个。
The system for copying parts of the genome into RNA for protein production comes from a virus called T7. This has become a workhouse of molecular biology—you can order up T7 RNA polymerase online and have it shipped to you on ice. In this case, the gene encoding T7 RNA polymerase was added to the SpudCell genome, and it was made by those artificial cells. 用于将基因组部分复制为 RNA 以进行蛋白质生产的系统来自一种名为 T7 的病毒。这已成为分子生物学的主力工具——你可以在线订购 T7 RNA 聚合酶，并让其在冰冻状态下运送给你。在本研究中，编码 T7 RNA 聚合酶的基因被添加到 SpudCell 基因组中，并由这些人造细胞自行制造。
The last element needed here is the translation of RNAs into proteins. And here, the researchers simply purified the translation machinery and supplied it to the SpudCells. They relied on a system developed by a team at the University of Tokyo, which added a tag to every protein required for translation and purified them using the tags. The Minnesota team simply purified these proteins and fed them into the system. 这里所需的最后一个要素是将 RNA 翻译成蛋白质。在此，研究人员直接纯化了翻译机器并将其提供给 SpudCells。他们依赖于东京大学一个团队开发的系统，该系统为翻译所需的每种蛋白质添加了一个标签，并利用这些标签进行纯化。明尼苏达团队只需纯化这些蛋白质并将它们喂入系统即可。
Feed me!
喂食！
That feeding was quite literal. For small, simple molecules, the researchers simply inserted a gene that encodes a pore protein into the SpudCell genome. This allowed small molecules and ions to diffuse into and out of the SpudCell. As long as the cells were placed in a solution with sufficient levels of these materials, the interior of the SpudCell would have decent concentrations of all of these. 这种“喂食”是字面意义上的。对于小型、简单的分子，研究人员只需在 SpudCell 基因组中插入一个编码孔蛋白的基因。这使得小分子和离子能够扩散进出 SpudCell。只要将细胞置于含有足够浓度这些物质的溶液中，SpudCell 内部就会拥有相当浓度的这些物质。
But the complex of proteins needed to make more proteins is far too large to go through a small pore. So the researchers encased these proteins and other large materials in a different membrane and then fed those to the SpudCells. To get the two membranes—one from the SpudCell, one from its food—to interact, the researchers added a tag to the pore protein that they had already been using. They then added something that would interact with that tag to the food membrane. This allowed the two to interact long enough to fuse, spilling the food into the interior of the SpudCell and adding additional membrane material to it. 但制造更多蛋白质所需的蛋白质复合物太大，无法通过小孔。因此，研究人员将这些蛋白质和其他大分子材料包裹在另一层膜中，然后喂给 SpudCells。为了让两层膜（一层来自 SpudCell，一层来自食物）相互作用，研究人员在他们已经使用的孔蛋白上添加了一个标签。然后，他们在食物膜上添加了能与该标签相互作用的物质。这使得两者能够相互作用足够长的时间从而融合，将食物倾入 SpudCell 内部，并为其增加了额外的膜材料。
This “feeding” process allows the SpudCells to continue making new proteins even after they would have exhausted their initial supply of raw materials. The added membrane material also increased the SpudCell’s size, literally causing it to grow. Normally, cell growth eventually results in cell division, splitting the membranes and their context between two new cells. But the SpudCells had no mechanism for achieving this. 这种“喂食”过程使得 SpudCells 即使在耗尽最初的原材料供应后，也能继续制造新的蛋白质。添加的膜材料也增加了 SpudCell 的体积，使其真正实现了生长。通常情况下，细胞生长最终会导致细胞分裂，将膜及其内容物分配到两个新细胞中。但 SpudCells 没有实现这一点的机制。
Initially, the researchers simply passed them through a wire grid and applied physical force to cause the membranes to split. But they eventually developed a system that could cause the pore proteins to clump by adding certain chemicals to the solution. That altered the membrane’s shape and eventually led to parts of it budding off. While this is a far more random process, it approximates cell division. 最初，研究人员只是让它们通过金属网并施加物理力来使膜分裂。但他们最终开发出了一种系统，通过向溶液中添加特定化学物质，使孔蛋白发生团聚。这改变了膜的形状，并最终导致其部分“出芽”脱落。虽然这是一个更加随机的过程，但它近似于细胞分裂。
So in a limited, carefully engineered sense, these “cells” could feed, grow, and divide, driven by proteins encoded by their own genome. As noted above, though, that genome was only distributed into the next generation of cells at random, and pieces of it were progressively lost over each generation. As a result, no SpudCells were taken past five generations in this work. 因此，在有限且经过精心设计的意义上，这些“细胞”可以在自身基因组编码的蛋白质驱动下进行摄食、生长和分裂。然而，如上所述，该基因组只是随机分配到下一代细胞中，并且其片段在每一代中逐渐丢失。因此，在这项工作中，没有 SpudCells 能够存活超过五代。
What can you do with a SpudCell?
SpudCell 有什么用？
Those five generations were enough to show that natural selection could operate on SpudCells. The researchers found they could alter their genome to tweak… 这五代足以证明自然选择可以在 SpudCells 上发挥作用。研究人员发现，他们可以改变其基因组来微调……