A look back at how we discovered all humans today come from a small group who lived in Africa 200 thousand years ago
1. Introducing Eve
This is a story of how we found our modern human origins in southern Africa. It is also one of perseverance through entrenched bias, endless technical criticisms, and of faith in the data.

回顾一下我们是如何发现今天所有的人类都源自于20万年前生活在非洲的一个小群体
1. “夏娃”简介
这是一个关于我们如何在南部非洲发现现代人类起源的故事,这也是一个在根深蒂固的偏见、无休止的理论批评之下对数据的信任而坚持不懈的故事。

Today, Rebecca L. Cann is a professor in the Department of Cell and Molecular Biology at the University of Hawai’i (UH), in Manoa. Back in 1987, a year after she had joined the faculty at the Honolulu campus of UH, her paper on the genetics of human origins was finally published. Her paper suffered a contentious two-year incubation at the prestigious British journal Nature because it totally upended the field of paleoanthropology — the study of human origins. Most of the eminent scientists in the field fought the paper fiercely.

今天,丽贝卡 · 卡恩是马诺阿夏威夷大学细胞和分子生物学系的教授,早在1987年,也就是她加入火奴鲁鲁大学一年之后,她关于人类起源的遗传学的论文终于发表了,她的论文在著名的英国期刊《自然》上经历了两年的争议,因为它彻底颠覆了研究人类起源的古人类学,该领域大多数知名的科学家都激烈地反对这篇论文。


2. Evolution and evolutionary trees…
Othniel Charles Marsh was a professor and paleontologist at Yale University who, in the 1870s, uncovered a complete series of fossils that beautifully traced the evolution of the horse. Marsh published his fossil history of the horse, which included a classic illustration of the serial changes in the equine forefoot.

2. 进化和进化树
奥斯尼尔·查尔斯·马什是耶鲁大学的教授和古生物学家,他在19世纪70年代发现了一系列完整的化石,这些化石精确地追踪了马的进化过程,马什出版了他的马化石史,其中包括马前脚连续变化的经典插图。


Illustration of the evolution of the equine forefoot (Marsh, 1874)

马前脚演化图 ( 马什,1874年 )

Marsh made many contributions to our understanding of evolution through paleontology. His success with the horse was spectacular and influenced scientists such as English biologist Thomas H. Huxley. Unfortunately, Marsh’s linear model of evolution was a bit too successful in capturing the public and academic imagination.
It was unfortunate because it was so wrong.

马什对我们通过古生物学理解进化作出了许多贡献,他在研究马的进化史方面的成功令人叹为观止,并影响了英国生物学家托马斯 · 赫胥黎等科学家,不幸的是,马什的线性进化模型在吸引公众和学术界的想象力方面有些过于成功。
之所以不幸,是因为它错得离谱。

Evolution is messy, and never proceeds in a straight line as typical museum displays and Marsh’s horse illustrations imply. Most of the fossils we unearth are not direct ancestors of modern species and are, instead, likely to be part of an extinct lineage. The bushy highly-branched evolutionary tree is a better model of the biological past.
Historically we have always tried to understand human origins through the fossil record, just like O.C. Marsh. However, there are numerous problems in using fossils alone to draw our human phylogenetic tree.

进化是混乱的,绝不会像典型的博物馆展览和马什的马插图所暗示的那样沿着一条直线进行。
我们挖掘出来的大多数化石并不是现代物种的直接祖先,相反,它们很可能是一个已经灭绝的谱系的一部分,丛生的、高度分枝的进化树高枝进化树是反映生物进化历史的一种更好的模型。
历史上,我们总是试图通过化石记录来了解人类的起源,就像马什一样,然而,仅仅使用化石来描绘人类的系统进化树还存在很多问题。

One problem is that hominid fossils are sporadic, fragmentary, and rare. Another is the uncertainty in geological dating methods or in dating specific fossil specimens. Yet another problem is that the size and shape of fossil bones are insufficient to prove an evolutionary relationship.
These are just a few reasons why our classical reliance on fossils was fundamentally flawed and could only lead to significant errors in our family tree. Modern evolutionary biology uses molecular and genetic tools, as well as fossils, to build more accurate phylogenetic trees and to overturn old prejudices.

其中一个问题是,类人猿化石是零星的、零碎的、罕见的,另一个问题是地质年代测定方法或特定化石标本年代测定的不确定性。关键还有一个问题:化石骨骼的大小和形状不足以证明进化关系。
这些只是我们对化石的传统依赖存在根本性缺陷的几个原因,只能导致我们人类的族谱出现重大错误,现代进化生物学利用分子和遗传工具以及化石来建立更准确的系统进化树,并推翻旧的偏见。

3. Using molecular clocks to build better evolutionary trees…
A phylogenetic tree built using hemoglobin mutations (Zuckerkandl and Pauling, 1965)


图:利用血红蛋白突变构建系统进化树 ( 扎克坎德尔、鲍林, 1965年 )





An evolutionary molecular clock using different proteins (Wilson et al., 1977)

图:使用不同蛋白质的进化分子钟



在上面威尔逊的分子钟图中,进化的时间尺度是在数千万年到数亿年之间,图表的斜率表明,我们可以很容易地解析出数千万年来的基因变化,然而,如果我们从短期的进化周期来看,我们无法解决这些变化ーー我所说的“短期”是指“不到几百万年”。

想象一下,用一个只有时针的钟来测量你在50米短跑中的时间,时针移动得太慢,无法精确测量短时间的比赛,就像蛋白质的变化太慢,无法测量短时间的进化一样。


A chondrocyte showing its nucleus (N) and mitochondria (M) (Robert Hunt, Wikimedia Commons).

图:一个软骨细胞的细胞核(N)和线粒体(M)

This is where mitochondria come in. Mitochondria are the powerplants of the cell, using oxygen to burn fuels in order to yield a cellular energy currency called adenosine triphosphate (ATP). Billions of years ago mitochondria were originally free-living aerobic bacteria that were engulfed by the last common ancestor of all eukaryotic cells (cells with a nucleus). Now they reside symbiotically in all animal, plant, and fungal cells, including ours. This is important for our story, since mitochondria come with their own DNA, separate from the DNA in the cell’s nucleus.

这就是线粒体的来源,线粒体是细胞的动力工厂,它利用氧气燃烧燃料,产生一种叫做三磷酸腺苷(ATP)的细胞能量货币(energy currency),数十亿年前,线粒体最初是自由生存的需氧细菌,被真核细胞(有细胞核的细胞)的最后一个共同祖先所吞噬,现在它们共生于所有的动物、植物和真菌细胞,包括我们的细胞,这对我们的故事很重要,因为线粒体有自己的 DNA,与细胞核中的 DNA 分离。


Two mitochondria from mammalian lung tissue (Louisa Howard, Wikimedia Commons)

图:两个哺乳动物肺组织的线粒体

This makes mitochondria a very practical and useful source of DNA for molecular clocks. They are common organelles, easy to separate from other cellular components like the nucleus, and yield a lot of mitochondrial DNA (mtDNA). Critically, for our purposes, mtDNA mutates at a much faster rate than genomic or nuclear DNA (gDNA) and can be used for short evolutionary times. We can think of mtDNA as the second hand on our clock for timing evolutionary sprints, where gDNA is alike the hour hand for timing ultra-marathons.

这使得线粒体成为一种非常实用和有用的分子时钟DNA来源,它们是常见的细胞器,很容易从细胞核等其他组成部分中分离出来,,并产生大量的大量线粒体DNA (mtDNA),至关重要的是,就我们的目的而言,线粒体 DNA 的变异速度比基因组或核DNA (gDNA)快得多,并且可以用于短暂的进化时期,我们可以把mtDNA看作是我们时钟上为“进化冲刺”计时的秒针,而gDNA则类似于为超级马拉松计时的时针。

Today, mtDNA is a key molecule used to understand human evolution. Still, it is important to recognize that mtDNA must be used with other biological molecules and with fossils to function accurately as a molecular clock.

今天,mtDNA(线粒体DNA) 是用来了解人类进化的关键分子,尽管如此,重要的是要认识到线粒体DNA必须与其他生物分子和化石一起使用,才能准确地发挥分子钟的作用。

5. Dating Eve…
Allan Wilson, who we met earlier developing evolutionary molecular clocks, was a full professor at the University of California Berkeley where he remained for his whole career. Rebecca Cann, whose paper revolutionized anthropology, got her Ph.D. under Wilson’s supervision at Berkeley. She was in Wilson’s lab for her post-doctoral training when she discovered Mitochondrial Eve and wrote her paper.

5. 遇见“夏娃”
艾伦 · 威尔逊,上文提到的开发进化分子钟的人,是加州大学伯克利分校的全职教授,他的整个职业生涯都在那里度过,丽贝卡 · 卡恩,她的论文彻底改变了人类学,在威尔逊的指导下,她在伯克利获得了博士学位,她在艾伦 · 威尔逊的实验室接受博士后培训时发现了粒线体夏娃,并写就了论文。

For her research with Wilson, Cann purified mtDNA from 145 placentas and two cell lines. The donors of the placentas covered a range of racial populations (20 Africans, 34 Asians, 46 Caucasians, 21 aboriginal Australians, and 26 aboriginal New Guineans). She then made a map of where the mtDNA differed from each donor. From these maps, Cann was able to calculate how much the sequences differed from person to person. Cann then used software to automatically calculate a phylogenetic tree from the mtDNA maps.

在与威尔逊的研究中,卡恩从145个胎盘和两个细胞系中纯化了mtDNA,胎盘的捐献者涵盖了不同的种族人群(20名非洲人、34名亚洲人、46名高加索人、21名澳大利亚土著人和26名新几内亚土著人),然后,她制作了一张地图,标明每个捐赠者的mtDNA的不同之处,从这些地图中,卡恩能够计算出人与人之间的序列差异有多大,然后,卡恩使用软件从mtDNA地图中自动计算出系统进化树。

The mtDNA data and analysis inferred an African origin, and more importantly that all the modern mtDNA descended from a single African woman. Using an estimate for the rate of mutations, Cann also inferred the African common ancestor of modern humans lived between 140 to 290 thousand years ago.

mtDNA数据和分析推断出非洲人的起源,更重要的是,所有现代mtDNA都源自一个非洲女性,利用对突变率的估计,卡恩还推断出现代人类的非洲共同祖先生活在14-29万年前。

6. Barbarians at the gate
Hordes of critics came pouring through every breach in the walls of Cann’s paper, criticizing her and her boss, Allan Wilson. Many of the leading anthropologists of the day were British men and Cann was an American woman. Anthropologists back then concentrated on fossils and associated them with cultural items, like tools and weapons. Cann used molecular biology and biochemistry to step deep into their realm of inquiry.

6. 门口的野蛮人
成群结队的批评者从卡恩论文的每一个缺口涌入,批评她和她的导师艾伦 · 威尔逊,当时许多著名的人类学家都是英国男性,而卡恩是美国女性,当时的人类学家把精力集中在化石上,并把它们与文化物品联系起来,比如工具和武器,卡恩运用分子生物学和生物化学深入到他们的研究领域。


Other criticisms came hard, fast, and for years — and some of them were right. There were indeed weaknesses and holes in Cann’s analyses. Using other molecules in addition to mtDNA would have been better. Calibrating the tree is an important step in analyzing any molecular clock. And so on. Nonetheless, Cann was ultimately right.

其他的批评也是来势汹汹,又狠又快,而且持续了数年之久——其中有些批评是正确的,卡恩的分析确实存在弱点和漏洞,除了线粒体DNA之外,使用其他分子会更好,校准进化树是分析任何分子钟的一个重要步骤,诸如此类,尽管如此,卡恩最终是正确的。


The focus of Vigilant’s paper was to present data on the mtDNA sequences from 189 individuals including 121 Africans from across five regions of Africa. Many of the criticisms of the 1987 Cann et al. paper were specifically addressed by Vigilant: in the new paper, she established a rate of evolution, calibrated the molecular clock with chimpanzee mtDNA, used native Africans instead of African Americans, used full mtDNA sequences rather than restriction enzyme digest maps, and applied rigorous statistical tests.

维吉兰论文的重点是提供来自189个人的线粒体DNA序列数据,其中包括来自非洲五个地区的121名非洲人,1987年卡恩等人论文的许多批评被维吉兰具体的解决了:
在新的论文中,她建立了进化速率,用黑猩猩线粒体DNA 校准分子钟,用非洲本地人代替非洲裔美国人,使用完整的线粒体DNA 序列而不是限制性酶消化图,并应用严格的统计测试。

Furthermore, Vigilant and her team used a new and more powerful computer program to generate a new tree. The program, Phylogenetic Analysis Using Parsimony, or PAUP, was written by David Swofford, then at the Illinois Natural History Survey, in Champaign, Illinois.Vigilant’s paper confirmed both the African origin of modern humans and the age of the common mtDNA ancestor at approximately 200 thousand years old, as in the 1987 paper.The paper was published in September of 1991. Wilson had died of leukemia in July of that year. He was fifty-six years old.

此外,维吉兰和她的团队使用了一种新的、更强大的计算机程序来生成新的进化树,该程序名为"Phylogenetic Analysis Using Parsimony",即PAUP,由当时伊利诺伊州香槟市的伊利诺伊州自然历史调查所的戴维 · 斯沃福德编写。
维吉兰的论文既证实了现代人类的非洲起源,也证实了人类共同线粒体DNA祖先的年龄与卡恩1987年的论文一样,约为20万年。
这篇论文发表于1991年9月,威尔逊于同年7月死于白血病,享年五十六岁。

8. Savages circle around the wagons
The new posthumous efforts by Wilson’s lab did not dampen the critics.
In January 1992, Alan Templeton published a letter in Science, the same journal that published Vigilant’s paper. Templeton reported that he re-analyzed the same mtDNA sequence dataset used by Vigilant et al. and got a different tree. The key argument was that Vigilant only did a single run of the PAUP program to generate her tree, and entered the data in sequential order. Templeton argued that many runs of the program with a randomized entry of the data were necessary to generate better and more accurate trees.

8. 野蛮人继续围城
威尔逊的实验室在他死后做出的新努力并没有打消这些批评。
1992年1月,艾伦 · 邓普顿在《科学》杂志上发表了一封信,也就是发表维吉兰论文的那家杂志。
邓普顿报告说,他重新分析了维吉兰等人使用的相同线粒体DNA序列数据集,得到了一棵不同的进化树,其关键的论点是,维吉兰只运行了一次 PAUP 程序来生成她的进化树,且是按顺序输入数据,邓普顿认为,为了生成更好、更准确的进化树,需要多次运行程序,随机输入数据。


Another powerful criticism came from David Swofford, the author of the PAUP software used to create the phylogenetic tree in the Vigilant et al. paper. Swofford joined two top Harvard researchers David Maddison and Maryellen Ruvolo in a paper that echoed Templeton’s, in saying that many randomized runs were necessary to get the best results from his software.
There were some supportive papers as well, including, bizarrely, one by Stoneking — who wrote supportively of Vigilant’s results after publicly denouncing them a few months earlier.

另一个强有力的批评者是戴维 · 斯沃福德,他是维吉兰等人论文中系统进化树程序PAUP的作者,斯沃福德与哈佛大学的两位顶尖研究人员大卫 · 麦迪森和玛丽莲 · 鲁沃洛共同发表了一篇与邓普顿的观点相呼应的论文,他们认为许多随机运行是必要的,这样他的程序才能得出最好的结果。
也有一些支持的论文,包括一篇奇怪的论文,作者是斯通金,他在几个月前公开谴责维吉兰的研究结果后,又写了一篇支持维吉兰研究结果的文章。

9. Where are we with Eve today
Slowly, over the years, different lines of evidence began to support Cann’s paper. First, gDNA evidence seemed to agree with mtDNA data. Then, dating methods improved, especially after the mid-1980s, and showed that African human fossils were older than humans outside Africa. After that, additional information showed that both anatomical and behavioral modernity in humans originated in Africa and that modern humans only migrated to the rest of the world after they were established in their home continent.

9. 今天的“夏娃”
多年来,慢慢地,不同的证据开始支持卡恩的论文,首先,gDNA证据似乎与mtDNA数据一致。
然后,测年方法得到了改进,特别是在20世纪80年代中期以后,并显示非洲人类化石比非洲以外的人类更古老,此后,更多的资料表明,人类的解剖学和行为学现代性都起源于非洲,现代人类只是在其母大陆建立了自己的家园后才迁移到世界其他地区。

In 2008, a review by J. H. Relethford in the journal Nature moved the debate forward. Modern humans, he said, then expanded out of Africa into the Old World. The debate, he said, was now about what happened next. Did modern humans extinguish and replace the archaic humans, such as Neanderthals? Or did some genetic mixture happen?
In 2016, a wide-ranging review by Chris Stringer in Philosophical Transactions of the Royal Society B also discussed modifications to the Recent African Origin model. Emerging data showed gene flow between Neanderthal, Denisovan, and Homo sapiens outside of Africa.

2008年,《自然》杂志上发表了一篇由 J · H · 瑞雷思福德撰写的评论,推动了这场辩论的前进,他说,“现代人”随后从非洲扩展到旧大陆,他说,现在争论的焦点是接下来会发生什么,“现代人”是否消灭并取代了古人类,如尼安德特人?还是发生了某种基因混合?
2016年,克里斯 · 斯特林格在《皇家学会哲学学报》上发表了一篇内容广泛的评论文章,也讨论了对近期非洲起源模型的修改,新出现的数据显示,尼安德特人、丹尼索瓦人和非洲以外的智人之间存在基因流动。

In retrospect, after over three decades, we can see Wilson and his team were right, even though they were also wrong on many points. They readily conceded where they were wrong, acknowledged their critics, amended their studies, and yet stuck with their main hypothesis of our recent African origin. Eventually, most of the paleoanthropology field converted to Wilson’s views.
We can ask: how it is that Wilson could have remained so steadfast in his convictions and research efforts, amid such pointed and competent criticism? Was it merely pig-headed stubbornness? Or was it a rationally informed and defensible minority position?

回顾过去三十多年,我们可以看到威尔逊和他的团队是正确的,尽管他们在许多方面也是错误的,他们欣然承认自己的错误,认可对他们的批评,修改他们的研究,但还是坚持他们的主要假设,即我们的非洲起源,最终,大部分古人类学领域都转向了威尔逊的观点。
我们不禁要问:
为什么威尔逊在面对如此尖锐而有力的批评时,仍能如此坚定地坚持自己的信念和研究努力?是愚蠢的顽固不化吗?或者,这是一种理性的、值得称赞的少数派立场?

An analogy might be the identification of the position of the sun and stars in the sky. In this analogy, Wilson made a single measurement during a cloudy day and reported the position of the sun and stars. His critics correctly pointed out that Wilson should have made multiple measurements, on clear days and clear nights using a calibrated device. Still, Wilson was correct about the position of the sun because its signal was strong enough to cut through the clouds. Meanwhile, Wilson’s critics made the fundamental error of throwing the baby out with the bathwater.

有一个恰当的类比,就是太阳和星星在天空中的位置的确定。
套入这个类比,威尔逊形同在一个阴天进行了一次测量,并报告了太阳和恒星的位置,他的批评者正确地指出,威尔逊应该使用校准设备,在晴朗的白天和夜晚进行多次测量,但是,威尔逊对太阳位置的判断是正确的,因为太阳发出的光线强到足以穿透云层。
与此同时,威尔逊的批评者犯了一个根本性的错误:把孩子连同洗澡水一起倒掉了。

So where are we with Eve today?
Eve herself appears to have faded behind the clouds. We don’t speak of her often today. More important is that the sunshine passed through the same obscuring clouds, signaling Africa as the recent birthplace of modern humans. As we develop more fossil and genetic data, we learn that our evolution is even more complicated, like we learned that horse evolution is messier and more complex than O.C. Marsh’s simple linear model. We carry within us small amounts of DNA from ancient hominids, evidence of infrequent but close relations with Neanderthals and Denisovans as we encountered them, and perhaps of others yet to be discovered. So, the story of our origins continues to unfold with growing complexity, beauty, and wonder the deeper we look.

今天“夏娃”的事怎么样了?
夏娃似乎已经消失在云层后面了,今天我们不常提起她,更重要的是,阳光穿过同样遮蔽的云层,表明非洲的确是现代人类的诞生地。
随着我们发展出更多的化石和基因数据,我们了解到我们的进化更加复杂,就像我们知道马的进化比马什的简单线性模型更加混乱和复杂,我们体内携带着少量古人类的 DNA,这些证据表明,在我们遇到尼安德特人和丹尼索瓦人时,与他们的关系并不密切,也许还有其他尚未被发现的物种,因此,我们起源的故事还在继续展开,越深入看越复杂,越看越美,越看越神奇。