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,均与这类以北欧神话"神域"命名的微生物存在亲缘关系。但由于该类微生物难以实验室培养,其细胞形态始终成谜。
最新发表于《自然》期刊的研究取得了突破性进展。由苏黎世联邦理工学院和维也纳大学组成的联合团队,首次在洛基古菌(Lokiarchaeum)中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),但其组装原理和动态特性与真核微管高度相似。
"这就像发现了生命进化拼图中遗失的关键碎片,"未参与研究的分子生物学家比尔·威克斯特德表示,"微管蛋白是真核细胞分裂过程中不可或缺的元件,其起源问题一直困扰学界。"
研究显示,这些管状结构可能参与细胞形态塑造、物质运输等关键过程。尤为引人注目的是,其动态组装特性与真核生物纤毛、鞭毛的演化理论高度吻合。剑桥MRC实验室细胞学家巴兹·鲍姆指出:"不同原丝数量可能对应不同功能,这为理解从古菌到真核生物的进化路径提供了新视角。"
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。由于该类微生物生长缓慢(需无氧环境且依赖共生细菌),后续研究将聚焦其细胞分裂机制,以验证微管蛋白是否在古菌中同样承担核心功能。耶鲁大学细胞生物学教授汤姆·波拉德表示:"当我们找到合适的研究对象并实现微管蛋白标记后,或将重塑对生命起源的认知。"
这项发现不仅填补了原核生物与真核生物之间的演化空白,更揭示了细胞骨架在生命形式从简单到复杂跃迁过程中的关键作用。正如研究者所言:"我们正在揭开地球生命最深奥的谜题之一——二十亿年前那个改变世界的进化奇迹究竟如何发生。"
中文翻译:
微管结构揭示复杂生命演化之谜
2010年,生物学家在北海淤泥中发现了一种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"(以北欧神话中诸神国度命名)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,但这些细胞本身极为罕见且难以实验室培养,使得显微观测长期无法实现。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?
随着培养技术逐步突破,研究者终于能观察这些微生物的生命活动。近期首批关于阿斯加德生物特性的研究报告,揭示了这些细胞内部令人震惊的新细节。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(维持细胞形态的内部结构)的某些组成部分与人类等复杂生物具有惊人相似性。
在人类细胞中,被称为微管蛋白的细胞骨架蛋白会相互嵌合,形成横跨整个细胞的拱形管状结构与轨道,一端生长的同时另一端分解。这些被称为微管的结构通过动态形成与分解的舞蹈,调控着真核生命的多个层面:操纵染色体、辅助细胞分裂、运载生物机器、作为马达蛋白轨道,并通过推拉细胞膜塑造其功能形态。
如今研究者在这些神秘细胞中发现了同类蛋白。它们扮演着什么角色?是否在远古时期曾帮助我们的祖先开辟新的演化路径?
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)、容纳基因组的细胞核,以及大量执行功能的膜状气泡或细胞器。它们可能具备螺旋桨状的鞭毛或毛发状的纤毛,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,宛如拥有地铁网络与繁忙交通的城市体系。
真核细胞的演化轨迹难以追溯——原核与真核生物之间不存在揭示进化路径的现存中间态。"我们缺失了漫长演化过程中中间形态完成多种突破的关键环节,"诺丁汉大学分子生物学家比尔·威克斯特德表示。真核细胞的创新性如此成功,使得任何近似形态都在竞争中消亡。
这正是阿斯加德古菌引发进化生物学家强烈兴趣的原因。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,也至少与那个开启自我改造之路的原始细胞存在亲缘关系。阿斯加德基因组中存在着此前仅见于真核生物的基因版本,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顺序,"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,或许能让我们破解二十亿年前的演化谜题。"
细胞骨架在这场演化革命中可能扮演了特殊角色。"它必然是地球首批真核细胞出现时的关键进化步骤,"悉尼科技大学微生物学家伊恩·达金解释道,"这些细胞以更大体积和更高复杂性为特征,需要精密的内部骨架进行组织。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"候选洛基古菌"中发现了类真核肌动蛋白。他们观察到这些蛋白在细胞内聚合成丝状结构。基因研究也标记出类微管蛋白基因,这一发现令人振奋。"微管蛋白是真核生物绝对不可或缺的细胞骨架蛋白,因其在细胞分裂中起决定性作用,"威克斯特德强调,"每次细胞分裂时微管都引导染色体分离,所有真核生物都遵循这一机制。"
但当时无人知晓洛基古菌用这些微管蛋白基因构建了何种结构。2022年的一项研究发现某类阿斯加德古菌的管状结构与真核生物差异显著。同年,沃尔韦伯却在显微图像中发现了异常结构——一道纤细优美的弧形构造。"它像一根横贯整个细胞的微小管状物,"他回忆道。通过系统筛查,研究团队确认虽然这类结构罕见,但确实存在于部分细胞中。尽管图像如外星传回的黑白照片般模糊,他们仍制定了破译方案。
微管蛋白的功能类似组合玩具。在真核生物中,α和β微管蛋白相互嵌合堆叠形成长杆,进而组装成管状结构(通常13根杆状体构成微管,不同细胞类型数量有异)。这些微管处于动态平衡中,持续组装新单元又周期性分解,通过生长收缩构建变幻莫测的细胞骨架。
研究团队重点考察了被命名为AtubA和AtubB的两种蛋白。通过在昆虫细胞中培育这些蛋白,他们获得足量样本进行试管组装实验。经过反复调试,终于观察到微管形成。"它们的组装速度相当快,"皮尔霍费尔表示。更令人惊叹的是,这些蛋白虽然仅由5根杆状体构成(而非真核生物的13根),但其结合方式与真核微管完全一致,同样具备生长分解的动态特性。"尽管形成了更适合微小细胞的微型管,相互作用机制却完全相同,"沃尔韦伯解释道。图像中的管状结构之谜就此破解。
未参与该研究的学者认为,这些微管结构的图像与特征发人深省。"它们不仅形成类微管细丝,还能聚合成束产生凸起,"威克斯特德指出。这种动态特性与真核生物纤毛和鞭毛的演化理论高度吻合。鲍姆则对杆状体数量差异特别感兴趣:"不同数量意味着结构功能差异,这为从阿斯加德到真核生物的演化路径提供了新思路。"
关键问题在于这些微管蛋白的实际功能。虽然实验室中能顺利组装,但活体洛基古菌中微管出现频率极低——沃尔韦伯筛查超过50个细胞才发现寥寥数例,表明培养细胞中这些结构并不活跃。更重要的是,真核细胞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测到。洛基古菌不仅生长缓慢,还需要无氧环境和共生细菌,使得研究异常困难。可能需要数月精心培养与定期成像,才能捕捉到细胞分裂的精细过程。
耶鲁大学研究细胞分裂的教授汤姆·波拉德表示:"或许存在具有类似微管蛋白但生命周期更短的阿斯加德古菌,我们需要找到合适生物体进行标记观测。"一旦科学家成功观测阿斯加德细胞分裂,就能确认微管是否在其中发挥核心作用。鲍姆指出可能存在意外发现:某些原核生物拥有无关的细胞骨架蛋白,微管可能并非必需。"实际上我们对古菌的分裂机制一无所知。"
"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了这些原始微生物,更在亿万年间定义了其后代的演化轨迹。
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.