The Journey of Man: A Genetic Odyssey (6 page)

The reason we have two copies of each chromosome is more complicated, but it comes down to sex. When a sperm fertilizes an egg, one of the main things that happens is that part of the father’s genome and part of the mother’s genome combine in a 50 : 50 ratio to form the new genome of the baby. Biologically speaking, one of the reasons for sex is that it generates new genomes every generation. The new combinations arise, not only at the moment of conception with the 50 : 50 mixing of the maternal and paternal genomes, but also prior to that, when the sperm and egg themselves are being formed. This pre-sexual mixing, known as genetic recombination, is possible because of the linear nature of the chromosomes – it is relatively easy to break both chromosomes in the middle and reattach them to their partners, forming new, chimeric chromosomes in the process. The reason why this occurs, as with the mixing of Mum’s and Dad’s DNA, is that it is probably a good thing, evolutionarily speaking, to generate diversity in each generation. If the environment changes, you’ll be ready to react.

But wait, you might say, why are these broken and reattached chromosomes any different from the ones that existed before? They were supposed to be duplicates! The reason, quite simply, is that they aren’t exact copies of each other – they differ from each other at many locations along their length. They are like duplicates of duplicates of duplicates of duplicates, made with a dodgy copying machine that introduces a small number of random errors every time the chromosomes are copied. These errors are the mutations mentioned above, and the differences between each chromosome in a pair are the polymorphisms. Polymorphisms are found roughly every 1,000 nucleotides along the chromosome, and serve to distinguish the chromosomes from each other. So, when recombination occurs, the new chromosomes are different from the parental types.

The evolutionary effect of recombination is to break up sets of polymorphisms that are linked together on the same piece of DNA. Again, this diversity-generating mechanism is a good thing evolutionarily speaking, but it makes life very difficult for molecular biologists who want to read the history book in the human genome.
Recombination allows each polymorphism on a chromosome to behave independently from the others. Over time the polymorphisms are recombined many, many times, and after hundreds or thousands of generations, the pattern of polymorphisms that existed in the common ancestor of the chromosomes has been entirely lost. The descendant chromosomes have been completely shuffled, and no trace of the original deck remains. The reason this is bad for evolutionary studies is that, without being able to say something about the ancestor, we cannot apply Ockham’s razor to the pattern of polymorphisms, and we therefore have no idea how many changes really distinguish the shuffled chromosomes. At the moment, all of our estimates of molecular clocks are based on the rate at which new polymorphisms appear through mutation. Recombination makes it look like there have been mutations when there haven’t, and because of this it causes us to overestimate the time that has elapsed since the common ancestor.

One of the insights that Wilson and several other geneticists had in the early 1980s was that if we looked outside of the genome, at a small structure found elsewhere in the cell known as the mitochondrion, we might have a way of cheating the shuffle. Interestingly, the mitochondrion has its own genome – it is the only cellular structure other than the nucleus that does. This is because it is actually an evolutionary remnant from the days of the first complex cells, billions of years ago – the mitochondrion is what remains of an ancient bacterium which was swallowed by one of our single-celled ancestors. It later proved useful for generating energy inside the cell, and now serves as a streamlined sub-cellular power plant, albeit one that started life as a parasite. Fortunately, the mitochondrial genome is present in only one copy (like a bacterial genome), which means that it can’t recombine. Bingo. It also turns out that, instead of having one polymorphism roughly every 1,000 nucleotides, it has one every 100 or so. To make evolutionary comparisons we want to have as many polymorphisms as possible, since each polymorphism increases our ability to distinguish between individuals. Think of it this way: if we were to look at only one polymorphism, with two different forms A and B, we would sort everyone into two groups, defined only by variant A or variant B. On the other hand, if we looked at ten polymorphisms with two variants each, we would have much better resolution, since the likelihood of
multiple individuals having exactly the same set of variants is much lower. In other words, the more polymorphisms we have, the better our chances of inferring a useful pattern of relationships among the people in the study. Since polymorphisms in mitochondrial DNA (mtDNA) are ten times more common than in the rest of our genome, it was a good place to look.

Rebecca Cann, as part of her PhD work in Wilson’s laboratory, began to study the pattern of mtDNA variation in humans from around the world. The Berkeley group went to great lengths to collect samples of human placentas (an abundant source of mtDNA) from many different populations – Europeans, New Guineans, Native Americans and so on. The goal was to assess the pattern of variation for the entire human species, with the aim of inferring something about human origins. What they found was extraordinary.

Cann and her colleagues published their initial study of human mitochondrial diversity in 1987. It was the first time that human DNA polymorphism data had been analysed using parsimony methods to infer a common ancestor and estimate a date. In the abstract to the paper they state the main finding clearly and succinctly: ‘All these mitochondrial DNAs stem from one woman who is postulated to have lived about 200,000 years ago, probably in Africa.’ The discovery was big news, and this woman became known in the tabloids as Mitochondrial Eve – the mother of us all. In a rather surprising twist, though, she wasn’t the only Eve in the garden – only the luckiest.

The analysis performed by Cann and her colleagues involved asking how the mtDNA sequences were related to each other. In their paper they assumed that if two mtDNA sequences shared a sequence variant at a polymorphic site (say, a C at a position where the sequences had either a C or a T), then they shared a common ancestor. By building up a network of the mtDNA sequences – 147 in all – they were able to infer the relationships between the individuals who had donated the samples. It was a tedious process, and involved a significant amount of time analysing the data on a computer. What their results showed were that the greatest divergence between mtDNA sequences was actually found among the Africans – showing that they had been diverging for longer. In other words, Africans are the oldest group on the planet – meaning that our species had originated there.

Figure 2 Proof that modern humans originated in Africa – the deepest split in the genealogy of mtDNA (‘Eve’) is between mtDNA sequences from Africans, showing that they have been accumulating evolutionary changes for longer.

One of the features of the parsimony analysis used by Cann, Stoneking and Wilson to analyse their mtDNA sequence data is that it inevitably leads back to a single common ancestor at some point in the past. For any region of the genome that does not recombine – in this case, the mitochondrion – we can define a single ancestral mitochondrion from which all present-day mitochondria are descended. It is like looking at an expanding circle of ripples in a pond and inferring where the stone must have dropped – in the dead centre of the circle. The evolving mtDNA sequences, accumulating polymorphisms as they are passed from mother to daughter, are the expanding waves, and the ancestor is the point where the stone entered the water. By applying Zuckerkandl and Pauling’s methods of analysis, we can ‘see’ the single ancestor that lived thousands of years ago, and which has mutated over time to produce all of the diverse forms that exist
today. Furthermore, if we know the rate at which mutations occur, and we know how many polymorphisms there are by taking a sample of human diversity from around the globe, then we can calculate how many years have elapsed from the point when the stone dropped – in other words, to the ancestor from whom all of the mutated descendants must have descended.

Crucially, though, the fact that a single ancestor gave rise to all of the diversity present today does not mean that this was the only person alive at the time – only that the descendant lineages of the other people alive at the same time died out. Imagine a Provencal village in the eighteenth century, with ten families living there. Each has its own special recipe for bouillabaisse, but it can only be passed on orally from mother to daughter. If the family has only sons, then the recipe is lost. Over time, we gradually reduce the number of starting recipes, because some families aren’t lucky enough to have had girls. By the time we reach the present century we are left with only one surviving recipe –
la bouillabaisse profonde.
Why did this one survive? By chance – the other families simply didn’t have girls at some point in the past, and their recipes blew away with the
mistral
. Looking at the village today, we might be a little disappointed at its lack of culinary diversity. How can they all eat the same fish soup?

Of course, in the real world, no one transmits a recipe from one generation to the next without modifying it slightly to fit her own tastes. An extra clove of garlic here, a bit more thyme there, and
voilà
! – a bespoke variation on the
matrimoine
. Over time, these variations on a theme will produce their own diversity in the soup bowls – but the recipe extinction continues none the less. If we look at the bespoke village today we see a remarkable diversity of recipes – but they can
still
be traced back to a single common ancestor in the eighteenth century, thanks to Ock the Knife. This is the secret of Mitochondrial Eve.

The results from the 1987 study by Cann and her colleagues were followed up by a more detailed analysis a few years later, and both studies pointed out two important facts: that human mitochondrial diversity had been generated within the past 200,000 years, and that the stone had dropped in Africa. So, in a very short period of time – at least in evolutionary terms – humans had spread out of Africa to
populate the rest of the world. There were some technical objections to the statistical analysis in the papers, but more extensive recent studies of mitochondrial DNA have confirmed and extended the conclusions of the original analysis. We all have an African great-great … grandmother who lived approximately 150,000 years ago.

Darwin, in his 1871 book on human evolution
The Descent of Man, and Selection in Relation to Sex
, had noted that ‘in each great region of the world the living mammals are closely related to the extinct species of the same region. It is therefore probable that Africa was formerly inhabited by extinct apes closely allied to the gorilla and chimpanzee; and as these two species are now man’s nearest allies, it is somewhat more probable that our early progenitors lived on the African continent than elsewhere.’ In some ways this statement is incredibly far-sighted, since most nineteenth-century Europeans would have placed Adam and Eve in Europe or Asia. In other ways it is rather trivial, since apes originated in Africa around 23 million years ago, so if we go back far enough we are eventually bound to encounter our ancestors in this continent. The key is to give a date – and this is why the genetic results were so revolutionary.

Anthropologists such as Carleton Coon had argued for the origin of human races through a process of separate speciation events from ape-like ancestors in many parts of the world. This hypothesis became known as multiregionalism, and it persists in some anthropological circles even today. The basic idea is that ancient hominid, or humanlike, species migrated out of Africa over the course of the past couple of million years or so, establishing themselves in east Asia very early on, and then evolving
in situ
into modern-day humans – in the process creating the races identified by Coon. To understand why this theory was so widely accepted, we need to leave aside DNA for a while and rummage around in some old bones.

Linnaeus named our species
Homo sapiens
, Latin for ‘wise man’, because of our uniquely well-developed intellect. Since the nineteenth century, however, it has been known that other hominid species existed
in the past. In 1856, for instance, a skull was discovered in the Neander Valley of western Germany. In pre-Darwinian Europe the bones were originally thought to be the remains of a malformed modern human, but it was later found to be a widespread and distinct species of ancestral hominid, christened Neanderthal Man after the site of its discovery. This was the first scientific recognition of a human ancestor, and provided concrete evidence that the hominid lineage has evolved over time. By the end of the nineteenth century the race was well and truly on to find other ‘missing links’ between humans and apes. And in 1890 a doctor working for the Dutch East India company in Java hit the jackpot.