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.
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. However, presently Cann’s paper forms the basis of the most widely held scientific view: that all living humans descend from a small population that dwelled in southern Africa a couple hundred thousand years ago. Specifically, the paper by Cann et al. said
“these mitochondrial DNAs stem from one woman who … lived about 200,000 years ago, probably in Africa.”
That one woman is commonly named African Eve or Mitochondrial Eve by the popular press. This is the story of how Eve came about, with the help of little cellular organelles called mitochondria.
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.
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.
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.
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.
3. Using molecular clocks to build better evolutionary trees…
In 1958, Emile Zuckerkandl, a former refugee from Nazi Germany, applied for a research position with Linus Pauling at the California Institute of Technology. Zuckerkandl learned chemistry in Pauling’s lab and applied that new knowledge to the analysis of hemoglobin (an oxygen-carrying protein) from a variety of primates and other animals. Zuckerkandl and Pauling noticed that the amount of variation in the sequence of amino acids (which are the building blocks of proteins) was related to the evolutionary distance between the species. This led to their seminal 1965 paper which originated the field of molecular evolution. The image pictured above is a scheme from their paper showing a phylogenetic tree based on hemoglobin sequences.
A couple of years later, in 1967, Allan C. Wilson and his graduate student Vincent M. Sarich published a paper on the rate of evolution of the protein albumin in primates. Wilson was a New Zealand farm boy who became a prominent biochemistry professor at Berkeley, and made a career out of doing things differently. Wilson and Sarich used a novel method of inferring evolutionary change by measuring the binding strength of antibodies to albumin. The pair of species with stronger antibody binding is more closely related than the pair with weaker binding. As with Zuckerkandl and Pauling’s results using hemoglobin amino acid sequencing, Sarich and Wilson found the strength of antibody binding to albumin varied in tandem with the hypothesized evolutionary distance.
Remember Allan Wilson’s name, since he plays a central role in this story.
By 1977, the concept of a ‘molecular clock’ had been established. The focus now centered around efforts by Allan Wilson and others to calibrate and validate molecular clocks (like in the graph below) with fossil and other evidence. Molecular evolutionary biology really flourished from here.
Today, molecular clocks are one of the standard tools we use to draw phylogenetic trees and are as important to our understanding of evolution as fossils. We need both molecules and bones to understand both our evolutionary history, and the relationships among our biological family.
4. Building molecular clocks with mitochondrial DNA…
In Wilson’s molecular clock graph above, the evolutionary timescale is in the tens to hundreds of millions of years. The slope of the graph shows we can easily resolve genetic changes over tens of millions of years. However, we cannot resolve changes if we look at short evolutionary periods — and by ‘short’ I mean ‘less than a few million years’. Imagine using a clock with only an hour hand to measure your time in a fifty-meter sprint. The hour hand moves too slowly to measure short races accurately, just as protein changes are too slow to measure short evolutionary times.
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.
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.
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.
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.
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.
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.
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.
The chief of the barbarians tearing at the walls was Milford Howell Wolpoff, a professor of anthropology at the University of Michigan since 1977 (a position he still holds today). Wolpoff was the chief and most vocal proponent of the Multiregional Hypothesis of human evolution, where he proposed that Homo erectus and Homo ergaster migrated from Africa across the globe about two million years ago, and that modern humans evolved from local populations of these species over the time. He immediately attacked the Out of Africa hypothesis christening it the “Out of Eden” hypothesis, and continues attacking it to this day.
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.
7. Buttressing the walls…
Four years after the first Eve paper by Cann et al., Wilson’s team published a follow-up paper in the journal Science in 1991, with Linda Vigilant as the lead author.
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.
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.
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.
In the same letters section of Science, another group also wrote a dissenting letter, which was signed by several scientists, and most importantly, by Mark Stoneking. Stoneking was co-author of both papers by Cann and Vigilant and had been both a Ph.D. and post-doctoral student in Wilson’s lab.
Mark Stoneking’s apparent recantation caused the popular media to celebrate the death of Mitochondrial Eve. ‘“African Eve” Backers Beat a Retreat’ crowed one editorial headline in the top-tier journal Science, where Vigilant had published her paper.
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.
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.
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.
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?
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.
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.
If you liked this, you might enjoy the much more in-depth version of this story of Mitochondrial Eve here.
Dating Eve with Mitochondrial DNA
Mitochondrial DNA and a bouquet of bones is the way to Eve’s heart and to the origins of anatomically modern humans…
You might also like my deeper dive into the good, the bad, and the ugly life of paleontologist O.C. Marsh here.
O. C. Marsh — Discoverer of Dinosaurs
The swashbuckling Yale paleontologist, the good, the bad and the ugly
Sticking to the theme of origins, here is one on the origin of life and the Last Universal Common Ancestor or LUCA.
LUCA — The Last Universal Common Ancestor
“…whilst this planet has gone circling on according to the fixed law of gravity, from so simple a beginning endless…
But, I think you will really like this one on the weird but wonderful eye-like structure in a single-celled, mobile, photosynthetic, predatory algae (pretty crazy already, huh?):