微小管状结构揭示复杂生命演化线索
内容来源:https://www.quantamagazine.org/tiny-tubes-reveal-clues-to-the-evolution-of-complex-life-20250908/
内容总结:
【科学前沿】微观管状结构揭示复杂生命演化关键线索
科学家通过研究阿斯加德古菌(Asgard archaea)的细胞骨架蛋白,首次发现其内部存在与真核生物相似的微型管状结构,为揭示20亿年前复杂生命的起源机制提供了关键证据。
2010年,科研人员在北海海底淤泥中发现一类特殊微生物——阿斯加德古菌。基因分析显示,人类、橡树、蓝鲸等所有携带细胞核与线粒体的真核生物,均与这类微生物存在演化关联。但由于该类微生物难以实验室培养,其细胞形态始终成谜。
近日,苏黎世联邦理工学院与维也纳大学的联合研究团队在《自然》期刊发表突破性成果。通过显微成像技术,研究人员在洛基古菌(Lokiarchaeum)细胞内观测到由微管蛋白构成的管状结构。这些被命名为AtubA和AtubB的蛋白质虽仅形成5根原丝构成的微型管状结构(真核生物通常为13根),但其动态组装方式与真核微管高度一致——能够持续生长和解聚,形成跨越整个细胞的支撑架构。
"这就像发现了生命演化的'缺失环节'",未参与研究的分子生物学家比尔·威克斯特德表示。微管蛋白在真核细胞中承担染色体分离、物质运输等核心功能,其起源机制一直是未解之谜。此次在古菌中发现功能相似的微管系统,暗示真核细胞的复杂内部结构可能源于古菌祖先的预先演化。
值得注意的是,这些管状结构在活体古菌中出现频率极低——研究人员筛查50余个细胞仅发现零星案例。研究团队推测,该结构可能仅在特定生命周期被激活,其具体功能仍需进一步验证。目前科学家尚未直接观测到阿斯加德古菌的细胞分裂过程,而该过程正是真核微管发挥关键作用的环节。
"我们现在需要找到生命周期更短的阿斯加德古菌变种",耶鲁大学细胞生物学家汤姆·波拉德指出,"通过荧光标记技术实时观测微管在细胞分裂中的行为,将是下一步研究重点"。
该项发现不仅为真核细胞起源的"内共生学说"提供新佐证,更揭示了细胞骨架系统在生命从简单向复杂演化过程中的核心推动作用。正如MRC分子生物学实验室专家巴兹·鲍姆所言:"我们正在揭开地球生命最深层的奥秘,或许终将重现20亿年前那场改变世界的细胞革命。"
中文翻译:
微小管状结构揭示复杂生命演化线索
引言
2010年,生物学家有了惊人发现:北海淤泥中存活着基因构成与人类高度相似的微生物。基因分析表明,人类、橡树、蓝鲸——所有拥有细胞核与线粒体的生物——都与这些被命名为"阿斯加德古菌"(以北欧神话众神居所命名)的微生物存在亲缘关系。二十亿年前,正是某个阿斯加德古菌的祖先脱离其族群,最终演化成了我们。
这个演化过程始终成谜,甚至长期无人知晓这些远古近亲的形态。虽然能从淤泥中提取阿斯加德DNA进行研究,但因其细胞极其稀有且难以实验室培养,无人能通过显微镜观察其真容。科学界对其形态的推测层出不穷:体型大小?触须覆盖?杆状还是完美球体?细胞内构与人类相似还是截然不同?
研究人员逐步攻克培养技术,终于得以观察其生命活动。如今,首批关于某些阿斯加德古菌生物学特征的研究报告,揭示了这些细胞内部令人震撼的新细节。苏黎世联邦理工学院马丁·皮尔霍费尔与维也纳大学克里斯塔·施莱珀实验室的最新论文指出,其细胞骨架(维持细胞形态的结构系统)中某些部分与人类等复杂生物的细胞骨架具有惊人相似性。
在人类细胞中,称为微管蛋白的细胞骨架蛋白会相互嵌合,形成高耸的管状拱廊与轨道,能够跨越整个细胞,一端生长另一端分解。这些被称为微管的管状结构通过形成、绽放与衰亡的舞蹈,控制着真核生物生命的诸多方面:处理染色体、辅助细胞分裂、运输物质、充当马达蛋白轨道,并通过推拉细胞膜塑造其功能形态。
如今研究人员发现,这些蛋白质同样存在于神秘的古菌细胞中。它们发挥着什么作用?是否在远古时期曾帮助我们的祖先开辟新的演化方向?
关键突破口
真核细胞在某些方面看似凭空出现。与更古老的细菌和古菌等原核生物不同,真核细胞拥有脂质双分子膜、提供能量的线粒体(源自自由生存的细菌)、包裹基因组的细胞核,以及大量执行功能的膜状气泡状细胞器。它们可能具备螺旋桨般的鞭毛或毛发状纤毛,体积远超原核细胞,内部空间布满微管蛋白与具有类似骨架功能的肌动蛋白丝,宛如拥有地铁系统与川流交通的都市。
真核细胞的演化轨迹一直难以追溯——原核与真核生物之间不存在揭示演化路径的活体中间态。"我们缺失了漫长演化长河中中间形态从事多种活动的证据,"诺丁汉大学分子生物学家比尔·威克斯特德表示。真核细胞的创新显然极具竞争力,使得任何近似形态都被淘汰。
这正是阿斯加德古菌引发演化生物学家浓厚兴趣的原因。从其DNA最初被发现时起,科学家就意识到它们即便不是中间态,至少也是那个开始自我改造并孕育新奇后代的原始细胞的近亲。阿斯加德基因组中存在着此前仅见于真核生物的基因变体,等待科学家揭示这些基因在全新语境中的功能。"这类信息能暗示真核细胞发育过程中线粒体、细胞核、生物膜或细胞器的演化次序,"剑桥MRC分子生物学实验室细胞学家巴兹·鲍姆指出。
"这正在揭开地球生命深层次奥秘的面纱,"他说道,"或许我们能破解二十亿年前那个关键事件的真相。"
过渡要素
细胞骨架在此演化过程中可能扮演了特别重要的角色。"它必然是地球首批真核生物出现时的关键进化步骤之一,"悉尼科技大学微生物学家伊恩·达金解释,"那些细胞以更大体积、更复杂结构为特征,需要精密的内部分子骨架进行组织。我们对其形成机制的认识存在巨大空白。"
2022年,生物学家开始发现诱人线索。皮尔霍费尔与博士后研究员弗洛里安·沃尔韦伯携手施莱珀团队,在阿斯加德古菌"Candidatus Lokiarchaeum ossiferum"中发现了酷似真核肌动蛋白的蛋白质,并观察到这些蛋白在细胞内聚合成丝。基因研究也标记出类似微管蛋白的基因。"或许可以论证,"威克斯特德表示,"微管蛋白是真核生物绝对不可或缺的细胞骨架蛋白,因为它主导细胞分裂。"他解释微管每次细胞分裂时引导染色体分离的作用:"没有真核生物能规避这个机制。"
但无人知晓这些洛基古菌用微管蛋白基因合成的蛋白质是否真能形成结构,又与真核生物有何异同。2022年某篇论文指出另一种阿斯加德古菌的管状结构与真核生物差异显著。但同年,沃尔韦伯在显微镜图像中发现了异常现象——那是一条纤细优雅的弯曲结构。"看起来像微型管状物,"他描述道,"一根贯穿整个细胞的管子。"通过查阅其他图像,他意识到虽然这类形态罕见,但确实存在于少量细胞中。灰度图像难以分辨构成材料,但他已构思出验证方法。
组装流水线
微管蛋白的功能类似组合玩具:在真核生物中,α与β微管蛋白相互嵌合,堆叠成长杆再组装成管状——通常13根杆状体构成一根微管(不同细胞类型数量有异)。这些微管处于精妙平衡中,时而叠加新单元,时而崩解重构,通过生长收缩形成动态骨架。
研究团队重点考察了被命名为AtubA与AtubB的两种蛋白。通过在昆虫细胞中培育并获得大量样本,他们将蛋白置于试管内观察反应。经过条件优化,终于欣喜地观察到管状结构形成。"组装速度相当快,"皮尔霍费尔表示。
深入分析揭示了奇妙特性:这些蛋白虽然仅由五根杆状体构成(而非真核生物的十三根),但结合方式与真核生物相同,形成微型管状结构,同样具备生长分解的动态特性。"尽管形成更细的管子以适应微小细胞,但其相互作用机制实则一致,"沃尔韦伯解释道。他们终于破解了图像中管状结构的来源。
未参与该研究的学者们认为,论文中的图像与微管结构揭示的奥秘发人深省。"它们既形成类微管细丝,又聚集成微管簇向外凸起,"威克斯特德指出。这种动态特征符合真核生物纤毛与鞭毛的演化理论,令他印象深刻。鲍姆则对杆状体数量差异感兴趣:"这很酷,既引发诸多疑问,又指明了从阿斯加德到真核生物的演化路径。"
核心问题在于微管蛋白的具体功能。虽然实验室中能顺利组装,但这些管状结构在活体洛基古菌中极为罕见——沃尔韦伯检查逾50个细胞仅发现零星案例,表明培养细胞中这些结构不常启用。更重要的是,真核生物中微管至关重要的细胞分裂过程,尚未在这些生物中被持续观察到。洛基古菌不仅生长缓慢,还需无氧环境与共生细菌,维持培养条件异常困难,需持续数月精心培育并定期成像才可能捕捉分裂过程。
耶鲁大学研究细胞分裂的汤姆·波拉德教授表示:"或许会发现拥有类似微管蛋白基因但生命周期更短的阿斯加德古菌,只需找到合适生物体并标记微管蛋白即可观察过程。"
一旦科学家成功观测阿斯加德细胞分裂,就能验证微管是否如同在真核生物中那样发挥核心作用。鲍姆指出可能存在意外:某些原核生物拥有无关的细胞骨架蛋白,微管蛋白或许并不参与分裂。"实际上我们对古菌的分裂机制一无所知,"他坦言。
"这正是细胞骨架的魅力所在,"鲍姆强调。生物需要组织内部结构、移动DNA与蛋白质、弯曲生物膜,不同生命形式已演化出各自解决方案。阿斯加德古菌中微管结构的发现,或许能帮助我们理解细胞骨架如何不仅塑造这些原始微生物,更在亿万年间影响了它们后代的生命形态。
英文来源:
Tiny Tubes Reveal Clues to the Evolution of Complex Life
Introduction
In 2010, biologists made a shocking discovery. Living in the mud of the North Sea were microorganisms whose genes looked a lot like ours. Genetic analysis revealed that humans, oak trees, blue whales — any living things whose cells have nuclei and mitochondria — are related to these microbes, which were named the Asgard archaea after the home of the Norse gods. Two billion years ago, it was an ancestor of an Asgard that diverged from its kin and eventually became us.
No one knows precisely how that happened, and for a long time, no one even knew what these long-lost cousins looked like. Asgard DNA could be fished out of the mud and studied, but the cells themselves were so rare and hard to grow in the lab that no one could scrutinize them under the microscope. There was an explosion of speculation among scientists about what they would be like. Would they be big? Small? Covered with tentacles, shaped like rods, perfectly spherical? Do their cells look like ours inside, or are they completely different?
Little by little, researchers have worked out ways to grow them and watch as they go about their lives. Now, some of the first reports about the biology of certain Asgards are revealing new, provocative details about the interior lives of these cells. The latest paper, from the labs of Martin Pilhofer at ETH Zurich and Christa Schleper at the University of Vienna, describes how a portion of their cytoskeleton — the set of cellular structures that give a cell its shape — is surprisingly similar to what can be found in more complex organisms such as ourselves.
In our cells, cytoskeletal proteins called tubulins snap onto each other to form soaring tubular arches and rails, capable of spanning entire cells, growing at one end while they fall apart at the other. These tubes, known as microtubules, form and bloom and decay in a dance that controls many aspects of eukaryotic life. They handle our chromosomes and help cells divide. They carry machines and act as tracks for motors. They push and pull cellular membranes, turning them into useful shapes.
Now, researchers have found that these proteins are in those mysterious cells. What are they doing there? And could they be part of what, so long ago, helped our ancestors strike out in new directions?
Intermediate Interest
The eukaryotic cell, in some ways, looks as though it came out of nowhere. Unlike bacteria and archaea, which are much older forms of life called prokaryotes, a eukaryotic cell has a double membrane of lipids around it. It also has mitochondria — remnants of formerly free-living bacteria — providing energy, a nucleus containing its genome, and a gaggle of membrane-bound bubbles, or organelles, transacting its business. It might have a propellor-like tail, or flagellum, or hairlike cilia. It is huge compared to the cells of prokaryotes. Its inner space is dense with filaments of tubulin and actin, another protein that plays a similar skeletal role. It is like a city, plumbed with subways and awash in traffic.
How the eukaryotic cell evolved has been hard to trace; there are no living intermediate states between prokaryote and eukaryote that could reveal its evolutionary trajectory. “We are missing a long time, a long branch of evolution, where intermediate forms did lots of other things,” said Bill Wickstead, a molecular biologist at the University of Nottingham. Eukaryotic innovations were apparently so successful that they outcompeted everything even remotely like them.
That is why the Asgards have provoked such intense interest from evolutionary biologists. From the very start, it was clear from their DNA that they might be, if not an intermediate state, then at least a relative of the original cell that began to transform itself and its descendants into something strange and new. There were versions of genes that had previously been seen only in eukaryotes, right there in the Asgards’ genome sequences, just waiting for biologists to see what they could do in this surprising new context. This is the kind of information that can imply what came first in the development of a eukaryotic cell: the mitochondrion, the nucleus, the membrane or the organelles, said Buzz Baum, a cell biologist at the MRC Laboratory of Molecular Biology Cambridge.
“It is lifting the veil on this deep mystery of life on Earth,” he said. “And you think — we might find out how this thing, 2 billion years ago, happened.”
Transition Elements
The cytoskeleton may have had an especially important role to play in this transition. “It must be one of the main steps that elaborated when the first eukaryotes arose on Earth,” said Iain Duggin, a microbiologist at the University of Technology Sydney in Australia. “Those cells are characterized by a much larger cell volume, much more complicated. To organize that, you need a sophisticated internal cytoskeleton. There’s a big gap in our knowledge of how those structures have formed.”
In 2022, biologists began to see some tantalizing clues. Pilhofer and the postdoctoral researcher Florian Wollweber, working with Schleper and a team of collaborators, revealed the presence of a protein very much like eukaryotic actin in an Asgard, called Candidatus Lokiarchaeum ossiferum. They could see these proteins joining together to make filaments in the cells.
Genetic work, too, flagged genes similar to tubulin, an intriguing finding. “I might make the argument,” Wickstead said, “that tubulin is the [cytoskeletal protein] that eukaryotes absolutely can’t live without because of its role in division.” Microtubules, he explained, are what guide our chromosomes into two separate cells each time a cell divides. “There’s no eukaryote that has managed to escape that.”
No one knew, though, if the proteins these Lokiarchaea made from these tubulin genes actually made structures, and whether they were similar to what eukaryotes have. One paper, published in 2022, found that tubules in another type of Asgard did not look particularly similar. But that same year, Wollweber spotted something unusual in a microscope image.
It was a slender, elegantly curving structure. “It looked like a small tube,” he said, “a tube that went across the entire cell.” Wollweber looked through other images of the Asgards and realized that although these shapes were rare, they were present in a small fraction of cells. It was hard to tell what they were made of from the images, which were grayscale, like transmissions from the surface of another planet. But he had a few ideas about how to find out.
Assembly Line
Tubulin functions a bit like Tinkertoys, the building toy with modular parts. In eukaryotes, two versions of the protein, alpha and beta tubulin, snap together. Then they stack on top of each other to make long rods, which then assemble into tubes — usually 13 rods make a tube, although the number can vary depending on the specific type of cell. These microtubules exist in a delicate equilibrium, stacking on new tubulin units for a while, then reaching a crisis and falling apart. They grow and shrink as needed, forming an ever-changing skeleton.
Wollweber and his colleagues wanted to see if the Lokiarchaea’s tubulin-like proteins behaved like the eukaryotic versions. They focused on two proteins in particular, which they dubbed AtubA and AtubB. By growing them in insect cells, they were able to harvest large amounts of both. Then they put them together in test tubes and waited to see what happened. It took some time to find the right ingredients and conditions, but to their delight, they eventually saw tubules forming. “We saw they assembled quite fast,” Pilhofer said.
A closer look at the tubules revealed something wondrous and strange. The proteins fit together in the same way as in eukaryotes, although the structures were made up of five rods, rather than 13, making a miniature tubule. They, too, grew and fell apart, as eukaryotic tubules do. “Even though they form a smaller tube, which might make sense in such a small cell, the interaction is actually the same,” Wollweber said. They had found the source of the tubes in the images.
To other researchers not involved in the project, the images in the paper and the revelations about the tubules’ structure are thought-provoking. “They are forming these filaments that look a lot like microtubules, but also forming clusters of microtubules, pushing out, making protuberances,” Wickstead said. This dynamic matches one theory of how eukaryotic cilia and flagella evolved, he added. “It was really striking to me.”
Baum is intrigued by the smaller rod number, pointing out that different numbers can imply different uses for the structure. “That’s cool,” he said. “It raises all kinds of questions and gives you a path from Asgards to eukaryotes.”
Chief among these questions is what the tubulins are doing. Tubules may assemble readily enough in the lab, but they seem to be very rare in living Lokiarchaea. Wollweber had to examine more than 50 cells to find just a handful. This suggests that whatever they are being used for is not happening often in these cultured cells. What’s more, cell division — for which microtubules are crucial in eukaryotes — has yet to be observed consistently in these organisms. The Lokiarchaea grow very slowly, and they require an oxygen-free environment and the presence of symbiotic bacteria, a situation which can be tricky to maintain. It would take months of carefully nurturing them, taking regular images, to see the gears of cell division set in motion.
Perhaps another Asgard with similar tubulin genes but a quicker life cycle will turn up, said Tom Pollard, a professor of molecular, cellular and developmental biology at Yale University who studies cell division. “Somebody just has to find the right organism,” he said, “and tag the tubulin and watch what happens.”
Once scientists can watch Asgard cells dividing, they will be able to see whether microtubules have the central role in that process that they have in eukaryotes. Baum points out that there may be surprises there. Some prokaryotes have unrelated cytoskeletal proteins — maybe the tubulins don’t get involved. “We have no idea that works in any archaea, actually,” he said.
“That’s why the cytoskeleton is interesting,” Baum continued. Organisms need to organize things, move DNA, move proteins and bend membranes, and various forms of life have come up with their own solutions to this. The discovery of tubules in Asgards may help us understand how the cytoskeleton helped to shape not only these primitive microorganisms but also their descendants over eons.