Nick Lane Traces Complex Life to Single Mitochondrial Energy Surge

尼克·莱恩将复杂生命的起源归结为一次线粒体能量激增 真核生物的复杂性在四十亿年间仅出现过一次，因为内化线粒体并剥离冗余基因突破了永久限制细菌和古菌的生物能量瓶颈。 尼克·莱恩（Nick Lane）探讨了生物学中最深刻的悖论之一：为何原核生物在四十亿年间形态上始终保持简单，而所有复杂生命均源于单一、未曾重现的真核共同祖先。他论证指出，尽管自然选择能够轻而易举地数十次演化出眼睛等复杂结构，但真核生物的架构需要一种罕见的内共生现象——即古菌内化了一种后来演变为线粒体的细菌。通过剥离超过99%的基因，这些被内化的“能量工厂”提供了巨大的能量盈余，从而实现了基因组和结构的大幅扩张。此外，解决宿主与内共生体之间由此产生的细胞内冲突，推动了有性生殖、两种交配型以及专门生殖系等标志性真核适应特征的演化。 地球上所有的复杂生命都拥有同一个真核共同祖先，该祖先在四十亿年间仅通过古菌宿主与细菌内共生体之间的一次独特内共生融合而诞生。 (8:29) 通过剥离超过99%的祖先基因，内部线粒体群释放了大量的ATP，使真核生物每个基因所拥有的能量比细菌高出三到四个数量级。 (24:16) 跨膜质子动力梯度在生命中几乎普遍存在，且极有可能起源于原始的碱性热液喷口，那里天然存在的3到4个pH单位的质子梯度早于生物膜出现。 (19:37) 在日本近海发现的一种神秘的10微米深海微生物体内拥有内共生体和单层膜细胞核，暗示着类真核生物演化过程一次罕见的独立重现。 (31:15)

Biochemist Nick Lane argues that the singular emergence of complex eukaryotic life was driven by an unrepeated endosymbiotic merger, which bypassed severe prokaryotic energetic constraints and channeled the evolution of defining cellular traits. The Evolutionary Bottleneck of Eukaryotic Origins (5:58) Prokaryotes underwent four billion years of evolution with massive populations and immense biochemical diversity, yet they remained structurally simple. In contrast, eukaryotes expanded genome sizes by up to 100,000 times compared to the largest bacteria and originated roughly 3,000 novel gene families. A single-celled ciliate like Paramecium possesses approximately 40,000 genes—double the protein-coding count of a human—and shares the same fundamental internal complexity found across all eukaryotes. The Singularity Paradox Under Natural Selection (8:29) Standard natural selection reliably produces convergent solutions to common pressures, as demonstrated by optical systems evolving independently 60 to 70 times across diverse lineages ranging from hydrothermal vent shrimp to trilobites. In contrast, all complex life traces back to a single common ancestor that already possessed the nucleus, sexual recombination, and complex organelles, leaving zero surviving evolutionary intermediates in the fossil or living record. Chimeric Genomes and the Ring of Life (12:27) Genomic sequencing shows that approximately 40% of eukaryotic genes match prokaryotic sequences, splitting into an archaeal informational core and a bacterial metabolic system. Rejecting Lynn Margulis’s Serial Endosymbiosis Theory due to the complete absence of predicted transitional forms, Lane highlights James Lake’s 'Ring of Life' model. In this framework, widespread lateral gene transfer among free-living bacteria explains the diverse metabolic lineages before a single, unrepeated engulfment of a bacterium by an archaeal host occurred. Endosymbiosis and the Bioenergetic Leap (19:37) Living systems universally rely on chemiosmotic proton gradients across membranes, an ancient mechanism that geochemist Mike Russell argued originated within the natural proton gradients of alkaline hydrothermal vents. While free-living bacteria are energetically limited by pumping protons across their outer cell surfaces, internalizing bacterial endosymbionts dismantled this barrier. Organellar Gene Loss and Trait Evolution (24:16) By shedding non-essential metabolic and structural genes within the host cell—human mitochondria retain just 37 or 38 genes from an ancestral ~4,000—endosymbionts unlocked massive metabolic surpluses. Lane calculates that eliminating just 5% of genes across 100 endosymbionts frees roughly 580,000 ATPs per second, allowing giant protists with up to 300,000 mitochondria to command three to four orders of magnitude more power per gene than bacteria. According to Lane and UCL colleagues like Zena Hadjivasiliou, subsequent intracellular genomic conflict and the need to preserve mitochondrial quality drove the emergence of sexual reproduction, two sexes, and dedicated germlines. Lane notes that while these evolutionary models provide a unifying framework for eukaryotic complexity, their testing remains challenging. An enigmatic 10-micron deep-sea organism found off Japan displays bacterial-like chromosomes and a single nuclear envelope with internal ribosomes, suggesting a potential independent recapitulation of endosymbiosis, but the destruction of the sole specimen during sectioning leaves its genome and broader implications unverified.

生物学家 Nick Lane 提出，复杂真核生物在地球 40 亿年历史中仅起源过一次，其根本原因在于原核生物受到膜生物能量学的严苛限制，必须通过内共生获取线粒体并大幅削减冗余基因，才能打破能量瓶颈并驱动复杂形态演化。 原核生物的形态停滞与真核生物的单一起源 (5:58) 尽管细菌和古菌经历了近 40 亿年的演化，并具备近乎无限的种群规模与惊人的生物化学多样性，但它们的形态结构始终保持极度简陋。与之相对，从单细胞的草履虫、变形虫到多细胞的动植物，所有复杂生命都由同一种真核细胞构成。真核生物不仅基因组规模可达细菌的 100,000 倍，还共享细胞核、内膜系统、吞噬能力和有性生殖等复杂特征。单细胞草履虫拥有约 40,000 个基因，约为人类蛋白质编码基因数量的两倍，并伴随真核生物的诞生涌现出约 3,000 个全新的基因家族。 Lane 指出，这种现象构成了自然选择理论中的深刻悖论。在自然界中，应对环境压力的复杂器官如眼睛曾独立演化过 60 至 70 次，形成了从水热盲虾的眼片到三叶虫方解石晶状体等迥异形态；而真核特征在整个地球历史上却只起源过一次。分子系统发育学显示，现代真核生物呈现放射状的“星状树”分布，其最后共同祖先（LECA）已经具备全部核心真核细胞器与特征，而自然界至今未发现介于简单原核生物与复杂真核生物之间的存活过渡中间形态。 嵌合基因组与化学渗透驱动的跨膜能量机制 (12:27) 真核生物在基因层面上呈现出独特的嵌合体特征：约 40% 可追溯的基因均等来源于细菌和古菌，其中信息处理机制源自古菌宿主，而代谢网络则源自细菌内共生体。针对细菌间广泛的水平基因转移现象，James Lake 提出了“生命之环”（Ring of Life）假说，认为这一嵌合体产生于一次不可逆的原核生物融合。此外，生命最核心的产能方式——利用电子传递链泵出质子以建立跨膜电荷储库，并驱动 ATP 合成酶旋转产生化学能的化学渗透耦合机制，在细菌、古菌和真核生物线粒体中几乎完全通用。 Lane 援引 Mike Russell 的理论指出，生命的这种能量机制很可能起源于 40 亿年前广泛存在的温和碱性深海热泉裂隙。富含氢氧根离子的碱性流体与酸性原始海洋在多孔矿物薄壁两侧交汇，天然构成了跨越 3 至 4 个 pH 值的质子梯度。这种地质环境不仅孕育了原始代谢，也塑造了生命的跨膜蓄能本能。然而，这也导致自由生活的原核生物终生受制于自身细胞外膜的质子泄漏与产能面积限制，无法在保持足够能量密度的前提下无限制膨胀细胞体积。 内共生基因精简带来的巨大能量飞跃 (24:16) 当古菌宿主细胞吞噬了演化为线粒体的细菌内共生体后，生命通过内部种群选择打破了能量屏障。在宿主内部受保护且养分充沛的环境中，内共生体之间发生复制速度的激烈竞争，促使其迅速剥离不再需要的细胞壁合成与代谢基因，仅保留维持局部呼吸氧化还原控制所需的核心基因组。现代人类线粒体仅保留了 37 或 38 个基因，相比标准细菌约 4,000 个基因（4 兆碱基）的规模，去除了超过 99% 的遗传负担。 Lane 构建的理论模型显示，即使一个宿主细胞内的 100 个内共生体仅各精简 5%（200 个）基因，在考虑每个基因产出约 2,000 个蛋白质、每个蛋白质约 250 个氨基酸及每个肽键消耗 5 个 ATP 的基准下，细胞在 24 小时周期内就能节约近 500 亿个 ATP，相当于每秒释放 580,000 个 ATP 的净盈余。这一能量富余足以支持每秒合成超过 4 微米的肌动蛋白微丝。而在包含数千乃至多达 300,000 个线粒体的真实巨型真核细胞中，真核生物分配到每个基因上的能量输出高出原核生物 3 到 4 个数量级（1,000 至 10,000 倍），正是这一巨大的能量跃迁为基因组扩张和细胞骨架等创新提供了代谢保障。 内共生体内在冲突与真核生物特征的塑造 (29:33) 宿主细胞内部容纳多个线粒体的结构同时也带来了严峻的演化冲突。各个线粒体在细胞分裂过程中会积累不同突变并发生不均等分配，导致细胞器质量控制面临极大挑战。Lane 指出，伦敦大学学院团队（包括 Zena Hadjivasiliou）的群体遗传学数学模型显示，解决这类胞内基因组冲突的需求，很可能是驱动真核生物演化出两大交配型（两种性别）、有性重组以及将生殖系与体细胞分离的核心动力。 这些针对细胞器品质筛选的内部机制，促使原本互不相干的复杂特征在极短的地质时间内被强制协同整合，奠定了日后寒武纪大爆发及多细胞复杂生命演化的结构基础。虽然自由生活细菌受限于能量物理法则而极难发生此类内共生，但一旦内共生契机发生，宿主与内共生体之间独特的基因与代谢博弈就会将整个谱系推向高度统一的真核生命模式。 Lane 强调其关于能量限制与内共生冲突的宏观模型虽然自洽但仍处于待检验的前沿假说阶段。尽管日本近海曾发现过一例形态呈现内共生特征但超微结构（单层核膜、核内含核糖体、2 纳米丝状遗传物质）迥异于常规真核生物的 10 微米深海奇特标本，但由于该唯一样本在制样切片中完全耗尽且后续十五年未再捕获，生命演化是否在其他路径上重演了真核化过程，仍是未解之谜。

[12:27] Nick Lane: Bacteria pass genes around between themselves as if it's loose change. [24:16] Nick Lane: The actual energetic advantage that eukaryotes have as a result of gene loss in their endosymbionts, which have always retained a few to keep control over respiration, it's absolutely huge, and I think that's what made that difference. [8:29] Nick Lane: All the complex life we know and that includes amoebae and and paramecia and so on is composed of this one cell type and all those cells are essentially the same... it only arose once.

[0:05] [Music] [0:13] well I'm going to really start uh where [0:16] Matthew left off um so this idea of [0:20] information uh and and Francis Crick was [0:24] his ideas [0:26] really went right to the bottom of [0:28] evolutionary biology as well it wasn't [0:30] only the code itself that he was talking [0:32] about and here again we see the the [0:34] terms information keep coming up but [0:36] this was 1958 and he said biologists [0:39] should realize that before long we shall [0:40] have a subject which might be called [0:42] protein [0:43] taxonomy now we'd talk about DNA rather [0:46] than proteins now the study of amino [0:48] acid sequences of proteins of an [0:50] organism and the comparison of them [0:51] between species it can be argued that [0:53] these sequences are the most delicate [0:55] expression possible of the phenotype of [0:57] an organism and that vast amounts of [0:59] evil tionary information may be hidden [1:01] away within them so this was it's quite [1:04] a well-known phrase now but this was [1:05] really the beginnings of phenetics as we [1:08] know it all the the the the gene which [1:11] Matthew showed at the very beginning [1:12] long long sequences of letters um we now [1:16] simply compare these sequences of [1:17] letters in in in different organisms now [1:21] the first person to actually do that was [1:23] lonus paing and again it's it's very [1:25] striking to me lus Pauling of course was [1:27] a physical chemist Crick a physicist by [1:29] background and these are the basic ideas [1:32] underpinning really the last half [1:34] century of research in evolutionary [1:36] biology so what what lus Pauling did [1:38] with Emil zuker candle in [1:40] 1962 was they started comparing uh [1:43] different proteins the number of [1:45] different amino acids in proteins from [1:47] different places so they compared [1:49] hemoglobin the beta chain of hemoglobin [1:52] the gorilla the horse and the human and [1:53] they found there's 20 different amino [1:55] acids if you compare a horse with a [1:58] human being there's only one different [2:00] amino acids if you compare the same [2:02] protein in a gorilla with a human being [2:04] so they also introduced this idea of a [2:07] molecular clock a rate of replacement of [2:11] amino acids over long periods of [2:13] evolutionary time and from fossil [2:15] evidence they figured out that horses [2:17] and humans must have diverged about 160 [2:20] million years ago something like that [2:22] and therefore the rate of change was [2:24] something in the order of [2:26] uh that there should be 10 amino acid ch [2:30] es over that period so it will be around [2:31] about 12 million years per amino acid [2:34] that changed all there about so this [2:36] this was the beginnings of [2:39] phenetics but hemoglobin of course is is [2:42] not conserved by everything if you [2:44] really want to try and get back to the [2:45] origins of life on Earth then you need [2:47] to find proteins or genes by this time [2:49] which are shared by absolutely every [2:51] living thing and the one thing which [2:53] every living thing really does uh is [2:56] make proteins as Matthew was talking [2:59] about you you you you've used the DNA as [3:01] the code you produce an RNA transcript [3:04] from that and that transcript then is [3:06] used to make proteins on the ribosomes [3:08] and all life has ribosomes and those [3:10] ribosomes are made up of various [3:12] effectively machine parts and one of [3:13] those machine parts is this so this is [3:15] the small subunit ribosomal RNA and Carl [3:18] wo picked on that back in the late 1960s [3:22] and started to compare the structures of [3:24] these so this is yeast the human one is [3:26] very similar to that this is ecoli you [3:28] can see these molecules are remarkably [3:30] similar right across all of life and so [3:33] what wo did uh was to compare these [3:35] molecules and he came up with this tree [3:37] of life and this is probably familiar to [3:39] most people I I I wonder how many people [3:42] are familiar with this three domains [3:43] Tree of Life could we have a show of [3:47] hands so probably about half or more [3:49] than half the Audience by the look of it [3:51] it's it's in all the textbooks and it's [3:53] basically it it's wrong actually and [3:55] I'll explain why um but it was shocking [3:59] at the time and it's still important now [4:02] it's these are the bacteria so we're all [4:05] familiar with bacteria again the archa U [4:08] see probably if you're familiar with [4:09] this tree you'll be familiar with the [4:10] ARA they look exactly the same as [4:12] bacteria you cannot tell the difference [4:14] we've actually known about some of them [4:15] methanogens for 400 years they were [4:17] first discovered by vter of all people [4:20] um but uh they look exactly the same we [4:23] had no idea that they were different but [4:24] you can see from the the length of the [4:26] branches on here that gives an [4:28] indication of the number number of [4:30] different uh sequence changes between [4:32] them and so the longer the branch the [4:34] more sequence changes there are and so [4:36] it gives a sense of time and evolution [4:40] and experimentation over evolutionary [4:42] time so here we are these are the [4:44] animals here the fungi plants and so on [4:46] very little variation there compared [4:49] with this enormous amount of variation [4:51] going on in these two other groups so [4:53] this is quite a shock there's an entire [4:55] group that nobody knew existed and then [4:58] we're consigned to a small Cor cor of [5:00] the tree which is pretty trivial and you [5:02] know is that really what the world looks [5:04] like well people have been sequencing [5:07] these genes ever since of course and and [5:08] this is ribosomal RNA again and just to [5:11] give you a sense this is where we are um [5:15] now it's [5:16] quite it's this this is something which [5:19] I think is really important in modern [5:20] science is the the amount of information [5:22] in here is absolutely massive does it [5:25] mean anything um well not a lot actually [5:30] and the reason it well you can [5:31] immediately see so animals are up here [5:33] and I I can't actually read my own [5:35] slides but the plants are up there the [5:36] fungi are down here look at this little [5:38] bit the bacteria and the archa are down [5:40] there they're a vanishingly small part [5:42] of that tree so already something's [5:44] going on here we're actually obsessed [5:46] with animals and plants and we sequenc [5:47] them all and probably they've not [5:49] included everything on here anyway but [5:51] if we go back it's a very different [5:53] picture to this so and this is one gene [5:58] now the question that I think the the [6:00] big question that I'm interested in here [6:01] is what on Earth was happening down here [6:03] so these groups had essentially 4 [6:05] billion years of evolution going right [6:08] back to 4 billion years ago and [6:10] effectively infinite population sizes [6:12] and and that's what they look like um [6:14] you know what have they achieved in all [6:16] of that time almost nothing it's [6:18] shocking they you know in their [6:19] biochemistry they're amazingly complex [6:22] but in in terms of their appearance [6:23] their structure their morphology they're [6:26] shockingly simple why didn't they get [6:28] any further what was happening down here [6:31] that wasn't happening over there why is [6:32] it that Carl wos came up in that group [6:35] but but you know why can't we have a [6:38] bacterial human why why doesn't that [6:40] happen well it's not only at the level [6:44] of large multicellular organisms this is [6:46] really written deep into the structure [6:48] of cells themselves so this is a bug [6:50] standard Alo you'll find that in any [6:52] Pond uh you leaner this is a relatively [6:54] complex bacterium um it's even got a [6:57] little compartment that some people have [6:58] said maybe that's nucleus it's not but [7:01] uh it you know the reason you can't see [7:03] it very well is this is roughly to scale [7:05] uh and so this is a single celled alga [7:10] when you get a whole lot of them they [7:11] form a scum um and you don't need to [7:14] know what any of these things are this [7:15] is the nucleus these are these are [7:17] chloroplasts in fact but you don't need [7:18] to know what any of these things are to [7:20] appreciate that there's an awful lot [7:21] going on and it's very big um and the [7:25] same goes for the number of genes they [7:26] have you know 3,000 families of new [7:29] genes seem to have Arisen with just this [7:32] group so and they can have genes genome [7:35] sizes up to about 100,000 times larger [7:38] than the largest known bacterium so [7:40] enormously [7:41] larger and this is just to give you a [7:45] sense that it's actually quite hard any [7:47] any suggestions for what the cell on the [7:49] left might be there or indeed the cell [7:51] on the right for that [7:55] matter okay so this is parium again [7:58] you'll find it in ponds and this is a [8:00] human pancreatic Asar cell it's pretty [8:03] hard to tell the difference between them [8:05] certainly in terms of their overall [8:06] complexity now parami actually has [8:08] 40,000 genes it has TW twice as many [8:11] genes as humans have it's a large [8:13] complex organism but it's a single cell [8:15] and so the my point is that UK cariot [8:18] this group of complex cells are just [8:21] enormously more complex than than than [8:23] bacteria or ARA something happened and [8:26] we don't really know what it is so [8:29] there's a paradox there and it's a [8:30] paradox about natural selection itself [8:33] so essentially the problem is that all [8:36] the complex life we know and that [8:38] includes Amber and and and parami and so [8:40] on is composed of this one cell type and [8:42] all those cells are essentially the same [8:44] it's very difficult to tell the [8:45] difference between them they all share a [8:47] long list of you know hundreds of or [8:49] thousands of traits in common it only [8:52] arose once we all share a common [8:55] ancestor and that common ancestor by [8:56] definition arose once you could say [8:58] perhaps there were lots of other Origins [9:00] as well but there's no trace of it [9:01] anywhere in biology so you know it's [9:04] make believe it might have happened but [9:05] there's no evidence for it um we all [9:08] share these traits procaryotes that [9:10] means the bacteria and the ARA they show [9:13] essentially no sign of evolving any of [9:14] those traits they have I showed you the [9:17] the nuclear light compartment that's [9:19] about as good as it gets so there are [9:21] there are steps in the direction but [9:23] really nothing very impressive in [9:25] comparison to what UK carriot do now if [9:27] all of those traits if the nucleus or if [9:29] sex for example arose step by step As [9:32] Natural Selection says it must uh and [9:35] each of those steps offered some small [9:36] Advantage which I'm not disputing at all [9:39] that's what happened then why did none [9:41] of them arise in bacteria or ARA well we [9:45] can begin to get another clue well [9:48] actually let me before I get onto that [9:49] let me just uh give an indication of why [9:52] this is really a paradox so the eye for [9:55] example eyes have Arisen on at least 60 [9:58] or 70 different occasions independently [10:00] from a light sensitive spot on some kind [10:02] of an early worm so there are some genes [10:04] in common some regulatory genes in [10:06] common but all of they independently [10:08] recruited all the rest of the genes [10:10] required to make an eye and so these [10:11] These are these are eye flaps on on on [10:14] blind shrimps that live in hydrothermal [10:16] vents these are scallop eyes fantastic [10:18] things this is an eye spot in udina uh [10:21] so it's a single cell ala that I showed [10:23] you before this is a trilite I I won't [10:25] go through the list but they're all [10:27] morphologically completely different [10:29] it's exactly what natural selection will [10:30] predict different environments different [10:33] circumstances you end up with different [10:35] types of eye arising on multiple [10:37] occasions so why didn't that happen with [10:39] sex or with the nucleus or with [10:41] phagocytosis the ability to engulf other [10:44] cells so here's the beginning of a clue [10:46] this is another tree what we would call [10:48] a star tree this is the the common [10:50] ancestor of all ukari um [10:53] now you might think that UK carry it so [10:56] split up into plants and animals and [10:58] fungi I'm afraid that ter out not to be [10:59] true as well this all turns out from the [11:01] information of comparing all of these [11:03] genomes so here we are the metazoans [11:05] there are the fungi plants are over here [11:07] somewhere these are the super groups of [11:09] UK carots have you ever heard of Chrome [11:12] alilet or unicons or rise area most [11:15] biologists haven't either I mean these [11:16] are these are only evolutionary [11:18] biologists care and only people who care [11:20] about the evolution of UK carots care [11:21] about these terms but it's a very very [11:23] striking and different portrayal to [11:25] anything that people had expected and it [11:29] two things to note from this one of them [11:30] is that these branches here there's very [11:32] little variation there was some kind of [11:34] a big bang radiation very early on and [11:37] then there's far more variation within [11:39] the groups than there is between the [11:40] ancestors of the groups the other thing [11:42] is this black hole at the center is [11:44] pretty symbolic because that common [11:47] ancestor of all UK carats had all of [11:49] these traits it had basically [11:52] everything and we don't know where they [11:54] came from so we start out with some kind [11:57] of a bacterium let's say it's a complex [11:59] one like this there's a recent paper [12:01] that people may have heard of saying [12:02] there a group of AR ARA called the Loki [12:05] arot which are perhaps some kind of [12:07] missing link but they are not um they [12:09] are basically similar to this so we [12:12] start here this is all we have evidence [12:15] for and there are no surviving [12:16] evolutionary intermediates whatsoever so [12:18] there's very very little to go on to say [12:20] well how did the nucleus arise why did [12:22] the nucleus arise what about sex what [12:24] about all these things how can we [12:25] possibly get those [12:27] questions well we can get at them and [12:30] again we can get at them by looking uh [12:32] at Gene sequences some genes sitting in [12:35] our own [12:36] nucleus are very comparable to bacterial [12:39] genes if you lay out their sequences and [12:41] you compare them so the the ribosome [12:43] genes for example that I mentioned we [12:45] have them and you can compare them with [12:46] bacteria and you can compare them it [12:48] turns out that we have um large numbers [12:52] of genes that are basically quite [12:53] similar to bacterial genes and we have [12:55] large numbers of genes which are [12:56] basically similar to AR genes we are [12:59] some kind of chimera we also have a [13:01] large number of genes which don't [13:02] compare at all with either of those [13:04] groups but at our basis about 40% of our [13:06] genes do compare with with procariotas [13:10] the strange thing about this is this [13:12] this is these are the groups that they [13:13] are most similar to so you take a gene [13:17] you compare the sequence and you say of [13:18] all the bacterial genes that we have [13:20] which group is it most similar to and it [13:22] turns out to be this one or that one or [13:24] this one and so all this shows is all [13:27] these all the UK carots the animals [13:29] plants fungus we all have these [13:31] bacterial genes and we have them [13:33] basically in the same way they're not [13:34] we've not been acquiring them over time [13:36] from bacteria different bacteria at [13:38] different times they all were there from [13:40] the [13:41] beginning but the trouble is they come [13:43] from all these different groups so how [13:45] can we interpret that this is a problem [13:47] the kind of problem that people wrestle [13:49] with which is to say there are several [13:51] possible explanations and we don't know [13:53] which one's true this is a fact but how [13:55] do you wrestle with it one possibility [13:57] would be Lim margulis to serial [13:59] endosymbiosis hypothesis Theory um I [14:03] don't like that very much but it does [14:05] make predictions it makes predictions [14:07] that it's serial for a start you have a [14:09] whole series and actually not enough [14:11] that she's got three or four of them [14:12] here people have been looking for this [14:14] group for 30 or 40 years and never found [14:16] a single thing from that group there so [14:19] that's why I don't like this as a as a [14:22] theory very much but it also says serial [14:24] and that means one after another and [14:26] they don't all arrive at the very [14:28] beginning so it doesn't really explain [14:31] that this begins to so this is um Ford [14:35] ditt wrote a great article entitled [14:37] taking an axe to the tree of life he [14:39] really does not like the Tree of Life um [14:42] why because of lateral Gene transfer so [14:44] what bacteria do is they pass genes [14:46] around between themselves as if it's [14:47] loose change uh so they pass all their [14:50] genes onto the onto the daughter cells [14:52] but then the daughter cell grabs one [14:54] from here and one from there and [14:55] everything gets mixed up and so if you [14:57] try and track back a tree of life well [14:58] may maybe you end up with a mess like [15:00] that again it's very hard to know it's [15:02] very hard to prove what came from [15:05] where if we make a simple assumption [15:08] which is that the common ancestor of all [15:10] of life had a genome which was basically [15:13] similar to a modern bacterial genome [15:15] let's say it had 4,000 genes or [15:17] something then you can constrain the [15:19] amount of lateral Gene transfer that [15:20] probably must have happened over and and [15:22] this is the picture that you get um so [15:25] there is some sign of vertical [15:27] inheritance but it's a mess [15:30] I mean just think of the of the [15:31] ribosomal RNA tree that I showed you [15:33] with this rather spurious sense of [15:35] precision that everything is beautifully [15:36] laid out we know exactly how [15:38] everything's related to each other we do [15:39] not um this gives a sense of the scale [15:42] of the mess but it also gives a sense of [15:45] where the answer might be so if this was [15:47] actually a singular event so two one [15:51] bacterium and one archon came together [15:54] and the reason that all those genes seem [15:56] to Branch with different groups is that [15:57] there' been lateral Gene transer ever [15:59] since between their between those groups [16:01] then that explains it this then is a [16:03] hypothesis which is testable in [16:05] principle at least it was a singular [16:08] event it wasn't multiple endosymbioses [16:11] it it wasn't something happening over [16:13] time it was just once and right there [16:16] and actually there's a lot of evidence [16:17] behind that now and I'm not going to go [16:18] into it today but it's what Jim lake [16:20] called The Ring of Life and I'm told he [16:23] sent a paper to Nature entitled one ring [16:25] to rule them all and unfortunately well [16:29] they accepted the paper but not the [16:31] title sadly they said this is Jim Lake [16:33] this is his Ring of Life uh and there's [16:35] there's a lot of evidence now that there [16:37] was the the host cell was an archon um [16:41] from from from from the ARA and there [16:44] was an endos symbion so a cell that got [16:47] inside it uh and that cell went on to [16:49] become the mitochondria so we all have [16:51] mitochondria the power houses of UK [16:54] cartic cells so it must have been [16:55] something a little bit like this so this [16:57] is the one example that we of today of a [17:00] bacterial cell this is actually a [17:02] cyanobacterium and you can see there's [17:03] some membranes in there these are thid [17:05] membranes in [17:06] cyanobacteria with cells living inside [17:09] them we have no idea how they got in [17:11] there they weren't engulfed by [17:12] phagocytosis because this is not a [17:14] fosite it has a cell wall but they're [17:17] there all right we just don't know how [17:19] they got there um but this is the [17:21] starting point then for for the [17:24] evolution of complex life if any of this [17:27] is true which it might not be [17:30] so they went on I'm suggesting to become [17:33] mitochondria this was the discovery of [17:35] mitochondria by Richard Altman um back [17:38] in 1895 and he he used an osmium uh [17:42] stain which actually dissolved the [17:43] cytoplasm pretty much leaving just the [17:45] mitochondria and the nucleus he thought [17:47] the nucleus was a food dump and these [17:50] were the elementary organisms what he [17:52] call bio blasts um and so he he had a [17:55] great job title extraordinary professor [17:57] of anatomy [18:00] love to get a job title like that one [18:01] day anyway but what we know now is that [18:05] um is that these mitochondria were [18:08] bacteria once and they're amazingly [18:10] successful if you think we have [18:12] something in the order of 500 trillion [18:14] mitochondria in our own bodies so I mean [18:17] you will hear it said that you know we [18:18] are we're only one one tenth human that [18:20] there's 10 times as many bacteria in the [18:22] microbiome well there's at least 500 [18:25] times as many bacteria as mitochondria [18:27] living in us we are basically 40 % um [18:31] mitochondrial and this is what's going [18:33] on in you right now so these are these [18:34] are these are mitochondria uh and these [18:36] membranes is where respiration is taking [18:39] place so as we um as we're burning food [18:43] in oxygen it's all going on in these [18:45] membranes inside these mitochondria [18:47] which were once bacteria and this is [18:49] roughly what's going on so in a in a [18:51] nutshell we're stripping electrons from [18:53] food hydrogen really from food the [18:55] electrons are flowing down this wire of [18:57] proteins so there's a current of [18:59] electrons to oxygen so we're stripping [19:01] them from food and the the protons so [19:04] hydrogen is made up of electrons and [19:05] protons the protons are pumped across [19:08] the membrane so the flow of electrons [19:10] the current of electrons flowing to [19:12] oxygen extrudes the protons across the [19:14] membrane we end up with something which [19:16] is a little bit like a hydroelectric Dam [19:18] so we've got a reservoir of protons on [19:20] one side uh and very few protons on the [19:22] other side and then we have a flow of [19:24] protons through the ATP synthes and that [19:27] produces What's called the the Universal [19:29] energy currency ATP so it's it's a very [19:32] peculiar way of going about things [19:33] nobody guessed that that was how life [19:35] was going to work now those little blobs [19:37] that I showed as a current of electrons [19:39] actually they're amazingly complicated [19:41] proteins it's been uh a Triumph of U of [19:46] of research over the last 30 or 40 50 [19:48] years to work out the exact structure [19:51] down to practically the scale of atoms [19:53] now of well this is the ATP synthes uh [19:57] these are the respiratory complexes of [19:58] pumping protons across the membrane so [20:00] we know in enormous detail how these [20:03] things work there's still some Mysteries [20:04] there's still people actively working on [20:06] it but we we know an awful lot what we [20:08] don't know is why life works that way [20:12] that was the problem that that Peter [20:13] Mitchell who came up with these idea in [20:15] the first place it was what motivated [20:17] him why you know how does not how does [20:20] respiration work actually but how do [20:22] bacteria keep their outsides different [20:24] to their insides it's one of these very [20:26] simple very deep questions [20:29] how do they keep different to the [20:31] outside world and if you can keep [20:32] different to the outside world he [20:34] realize that well stuff can flow in [20:35] again and you can take advantage of that [20:37] and so the flux of things into cells [20:40] give you a source of energy so this is [20:42] Peter Mitchell and Jennifer Moy so [20:44] Jennifer Mo did all the experiments [20:46] Peter Mitchell did all the thinking he [20:48] got the Nobel Prize she didn't um we can [20:51] debate the the pros and cons of that [20:53] later on but uh basically it was her [20:55] experiments that proved it um but it was [20:57] Mitchell who really conceived the ideas [21:00] who's to say what's most important in [21:03] science um why I'm not going to talk [21:06] there have been several leads to say I'm [21:08] going to talk about the origin of life [21:09] I'm afraid I'm not you're going to have [21:11] to read my [21:12] book I'm just going to say a word or two [21:15] about it [21:17] um how did these things start they're [21:19] Universal across all of life I I failed [21:21] to to to quote this lovely quote from [21:23] Leslie oel not since Darwin has biology [21:26] come up with an idea as counterintuitive [21:28] as those of say Einstein Heisenberg and [21:30] shring are the physicists are creeping [21:32] back in again here but you know [21:34] physicists are full of big [21:36] counterintuitive ideas there aren't very [21:38] many in biology the the the double helix [21:42] is an entirely intuitive idea Jim Watson [21:44] said you know it was so pretty it had to [21:46] be true you know but but the idea of [21:49] pumping protons across a membrane it's [21:50] so ugly that you think why on Earth does [21:52] it work like that and nobody can ever [21:54] remember the term chem osmotic [21:56] coupling so um the problem is that these [22:00] proton gradients they're as universal as [22:02] a genetic code now actually there's a [22:05] slight of hand in there because Matthew [22:06] said the genetic code is not actually [22:08] quite Universal and it's also true that [22:10] proton gradients are not quite Universal [22:12] either but they're more or less [22:14] Universal and the groups that don't use [22:15] them are obviously relatively recently [22:17] derived and live in Fairly peculiar [22:20] conditions so to in a broad brush stroke [22:22] they are Universal and that implies they [22:25] arose really early and that means that [22:27] we need to think about what kind of of [22:28] an environment it gives a pointer to [22:30] what kind of an environment life might [22:31] have Arisen in and I I I'm going to skip [22:34] over this very quickly these kind of [22:36] vents which were discovered only 15 [22:38] years ago called alkaline hydrothermal [22:40] vents uh down at the bottom of the [22:42] Atlantic seems that they're probably far [22:44] more common or would have been far more [22:46] common uh 4 billion years ago Mike [22:50] Russell who put these ideas forward over [22:52] the last 20 years or more has argued [22:54] that they electrochemical flow reactors [22:56] so it's not it's not like a black smoke [22:58] belching smoke out of the top it's a [23:00] Labyrinth of pores and the the [23:03] hydrothermal fluids W their way through [23:05] these pores so the important point for [23:08] us is that they have natural proton [23:10] gradients These Are alkaline fluids [23:12] going into what would have been a mildly [23:14] acidic ocean and so the inside has very [23:16] few protons the outside has lots of [23:18] protons [23:20] and they would have been across these [23:23] barriers in this microporous Labyrinth [23:26] and so this is the situation that we [23:27] have in these vents we've got large [23:29] concentrations of protons on the outside [23:31] low concentrations on the inside and [23:33] some kind of thin inorganic barrier [23:35] between the two this is what's going on [23:38] in all of life so this is a bacterium or [23:40] something it's the same thing it's [23:42] pumping protons out it's actively [23:44] pumping them out this is a thin membrane [23:46] this is orders of magnitude thinner than [23:48] that so I'm just exaggerating the the [23:50] the analogy here but it's about the same [23:53] order which is to say it's about three [23:55] or four pH units different between here [23:57] and there [23:59] now there's all kinds of reasons that uh [24:02] qu the question is really what use is [24:04] that without proteins without membranes [24:07] I I do discuss that in the book and I'm [24:09] not going to talk about it [24:11] now but for the last minute or two few [24:14] minutes [24:16] um I want to suggest that the problem [24:19] with [24:20] this is that they are constrained by [24:23] pumping across their membrane this is [24:26] how life started bacteria ARA all do [24:29] that in that way and then they're kind [24:31] of stuck with it so what was the good [24:33] thing about having this situation at the [24:35] origin of UK carats where you have an [24:37] endo Symon this goes on to become the [24:39] mitochondria um well the thing is that [24:42] these are cells it's not just a Cell [24:44] It's a population of cell and they can [24:45] compete among themselves and when they [24:47] do so very often if you can make more [24:49] copies of yourself in a given period of [24:50] time you will be better represented down [24:53] down in history and so if you get rid of [24:56] a few genes that you don't need for [24:58] example you make more copies of yourself [24:59] in a shorter period of time and so the [25:01] competition between these cells in this [25:03] population living within a cell they [25:05] tend to dump any genes that they don't [25:07] need and become simpler and rely on the [25:09] host cell for anything that they they [25:11] can do and in the end they lost almost [25:13] all of their genes we only have U 38 of [25:16] them left in our own mitochondria well [25:19] there are massive massive energetic [25:21] consequences of losing those genes so [25:23] just as a quick and slightly silly [25:25] thought experiment imagine that you've [25:27] got a cell and it it's got 100 Endo [25:30] symbiance so it's got a 100 bacteria [25:33] living inside it and let's say that it [25:35] has a standard bacterial genome so it's [25:38] got something like 4,000 genes four [25:40] megabases 4,000 genes it loses 5% of [25:43] them so these are the genes it normally [25:45] would use for making a cell wall to [25:47] protect itself it doesn't need that [25:48] anymore and they replicate a bit faster [25:50] if they lose those genes so it's lost 5% [25:53] of his genes so what's what's the Energy [25:55] savings that you get from losing those [25:57] genes from endos symbals well each of [25:59] those genes encodes a protein and those [26:02] proteins are uh produced in multiple [26:04] copies you you don't just make one [26:06] protein you make thousands of them on [26:08] average in a bacterium about 2,000 of [26:10] them and each protein is a string of [26:11] amino acids which are all linked [26:13] together on average 250 amino acids [26:16] linked together in a protein and it cost [26:19] you about 5 [26:20] atps to make to bind the two amino acids [26:24] together so you can work out the cost in [26:26] atps this energy currency um that you [26:29] would have to pay to build all of those [26:32] proteins well the answer is the cost is [26:34] something in the order of 50 billion [26:36] atps if we assume a 24-hour life cycle [26:40] that works out at 580,000 per second so [26:43] that's what you would save by not [26:46] expressing those genes in those 100 [26:49] endos symbiot what could you spend it on [26:51] well let's say let's have a let's have a [26:53] dynamic cytoskeleton something that will [26:55] allow you to move around what does that [26:57] actually cost there's no reason why you [26:59] should spend it on that but you could [27:00] spend it on that so what would it cost [27:02] well the length of the acting this it's [27:05] made of a filament but the filament is [27:06] lots of proteins joined together they [27:08] kind of gum together and each of those [27:10] monomers is 29 nanom in length uh so [27:14] there's the 35 uh monomers per Micron so [27:18] that's 35 proteins joined together per [27:20] per Micron um there's 374 amino acids in [27:24] each protein it's a Diemer and again [27:27] we're assuming atps per peptide bond so [27:29] the total cost is 131,000 atps to make [27:33] one micron of actin which means for [27:36] those savings you could make four [27:38] microns a second which is you know a [27:42] massive amount that's way more than any [27:44] bacterium actually does and that's [27:46] denovo synthesis starting from the start [27:48] so it really is it's a huge difference [27:51] now mitochondria didn't lose 5% of their [27:54] genes they lost 99% of their genes and [27:56] they're not limited to 100 a cell there [27:58] can be as many as 300,000 in a larger [28:01] Amber and so the actual energetic [28:03] advantage that you carots have as a [28:05] result of Gene loss in their Endo [28:08] symbion which have always retained a few [28:10] to keep control over respiration it's [28:12] absolutely huge and I think that's what [28:14] made that difference and we can quantify [28:16] that these are various different types [28:18] of bacteria including giant bacteria [28:20] there are some giant bacteria which are [28:22] which are visible to the naked eye [28:24] they're still only half a millimeter [28:25] long but they're you know that's pretty [28:27] big for a bacterium they have what's [28:29] called Extreme polyploidy thousands of [28:31] copies of their genome if you take all [28:33] of that into consideration these are [28:35] various numbers for bacteria this is the [28:37] metabolic rate so the power that they [28:39] have uh per Gene and these are ukar this [28:42] is a log scale so this is three or four [28:45] orders of magnitude more energy per Gene [28:48] that that uh this is uder again which I [28:51] was showing you earlier on this is a [28:53] large Amber so order to magnitude more [28:56] energy to do what you want with with [28:58] your genome to make that many more [29:00] proteins or to have that many more [29:02] genes so just for the last bit then um [29:06] coming back to [29:09] this can we get any insight into what [29:11] was going on down here well possibly [29:14] because if this if this is just a simple [29:16] a complex bacterium but it didn't evolve [29:19] by natural selection in a large [29:20] population what actually started out is [29:22] something more like that then we can [29:24] begin to constrain what was going on and [29:27] we've been doing some population [29:29] genetics uh on this in in the department [29:31] Zena vasu just finished her PhD [29:33] about a year ago working on this I'm not [29:35] going to talk about that now but you can [29:37] see immediately just looking at this [29:38] that if you have a population of [29:40] mitochondria within a cell they differ [29:42] they mutate in different ways they can [29:44] become different they segregate in [29:45] different ways and it takes quite a lot [29:48] of work to try and figure out how do you [29:50] how do the organisms constrain what's [29:53] going on here in fact the mechanisms are [29:55] almost certainly things like having two [29:57] Sexes having sex at all having a germ [29:59] line all of these can be shown that they [30:01] actually improve the quality of [30:03] mitochondria so I'm not going to say [30:05] more about that again if you're [30:07] interested you'll have to read the [30:10] book um but right up to the you know the [30:13] Cambrian explosion and the origin of [30:15] animals and germ lines and so on it's [30:16] it's all potentially explicable as [30:19] always with science these are neat ideas [30:21] they may not be true they may be [30:23] complete rubbish but at least we can [30:25] test them or we can try and find ways of [30:27] testing [30:29] so few conclusions complex cells the [30:32] eukariotic cell arose just once in 4 [30:34] billion years that's seems to be a fact [30:36] I can say more about that if people are [30:38] interested um it looks as if energy [30:41] constraints on bacteria uh demand some [30:43] kind of a rare endosymbiosis between [30:49] procariotas symbiot between the cells [30:51] living inside a host cell that's pretty [30:54] tough and it forces cells down [30:57] particular populations of cells down [30:59] particular Avenues it forces you to have [31:01] sex for example or to have two Sexes and [31:03] so we can begin to predict that the [31:05] resolution to those those uh conflicts [31:09] uh May account for why all UK carriers [31:11] share so many similar traits now I want [31:15] to leave you with this this was [31:17] discovered in case you think it's [31:18] pessimistic that life only complex life [31:21] only arose once in four billion years [31:23] maybe it's happening again off the coast [31:24] of Japan um so this was discovered about [31:27] 5 years ago and it's an intriguing title [31:30] on the paper a unique organism from the [31:32] deep sea um Pro carot or you car it they [31:37] don't know I don't know nobody really [31:39] knows but let's have a quick look at it [31:41] so it's about 10 microns long which is [31:44] substantially larger these are bacteria [31:46] here so it's substantially larger than [31:48] the average bacterium it has what looks [31:50] like a nucleus so this looks like [31:52] standard eukariotic nucleus it's got [31:55] some Endo symbion perhaps they're not [31:57] mitochondria but they could be something [31:59] like hydrogenosomes which are derived [32:00] from mitochondria um it's got a plasma [32:03] membrane and a cell wall and so on so to [32:05] a first glance this looks like a [32:07] standard UK carat but when you look more [32:09] closely well this is not a double [32:11] membrane all UK carats have a double [32:13] membrane around the nucleus this has a [32:16] single membrane around the nucleus all [32:18] UK carats have chromosomes with a [32:20] diameter of around about 30 nanometers [32:22] this has bacterial filaments with a [32:24] diameter of two uh nanometers um um we [32:29] don't know what what those are there's [32:31] no genome sequence for this we really [32:33] don't know very much these this model [32:35] modeling here those are [32:37] ribosomes no eukariotic cell that we [32:40] know of has ribosomes in the nucleus the [32:42] whole point of the nucleus is to exclude [32:44] protein synthesis from going on there [32:46] but here it's going on in the nucleus as [32:48] well as outside the nucleus um these [32:50] membranes inside the cell they are [32:52] nothing like the membranes that we see [32:54] the endoplasmic reticulum things like [32:56] that so this is not a UK carot and is [32:58] not a pro cariot I would say that what [33:01] this is is a bacterium that acquired [33:04] endo symbiance and which is [33:06] recapitulating eukaryotic Evolution it's [33:08] become larger it's accumulating genes um [33:12] it's got a nucleus it's going through [33:14] the whole thing all over again but we [33:16] only ever found one of them and they've [33:17] been looking for 15 years to try and [33:19] find another one and uh they've not [33:21] found it yet [33:23] so and they sectioned they took a [33:25] section of that which means we don't [33:27] have a genome sequence either so this is [33:29] how science goes we're just going to [33:30] have to wait and you are as well thank [33:33] you very [33:35] much what is the symbiotic relationship [33:38] the two organisms have that allows them [33:40] to be symbiots