Power, Sex, Suicide: Mitochondria and the Meaning of Life (44 page)

Perhaps the most bizarre method of excluding the male mitochondria is found in the giant sperm of some species of fruit fly (
Drosophila
), which can be more than ten times longer than the total male body length when uncoiled. The testes required to produce such mammoth sperm comprise more than 10 per cent of the total adult body mass, and retard male development markedly. Their evolutionary purpose is unknown. Such extraordinary sperm add far more cytoplasm to the egg than normal. What’s more, the sperm tail persists in the egg, raising the question of its fate. According to Scott Pitnick and Timothy Karr, at Syracuse University, New York, and the University of Chicago, respectively, the mitochondria fuse together during sperm development to form two enormous mitochondria, which extend the entire length of the tail. These two vast mitochondria fill 50 to 90 per cent of the total cell volume. They are not digested in the egg, but rather are sequestered throughout embryonic development,
ultimately in the midgut. The sperm tail can still be observed in the midgut of the larvae after hatching, and is defaecated out soon after birth, conforming to the spirit of uniparental inheritance, if in an oddly convoluted manner.

The fact that there are so many radically different methods of excluding the male mitochondria implies that uniparental inheritance evolved repeatedly, in response to similar selection pressures. This in turn suggests that uniparental inheritance was also lost repeatedly, and later regained by way of whatever trick was most readily pressed into service at the time. I suspect this means that losing uniparental inheritance was weakening but rarely fatal, and indeed there are some examples of mitochondrial mixing, or
heteroplasmy
, notably among the fungi and angiosperms. For example, in one large study of 295 angiosperm species, nearly 20 per cent of all the species examined showed some degree of bi-parental inheritance. Interestingly, bats, too, are often heteroplasmic. Bats are long-lived, vigorously active mammals, so it is curious that they are not compromised by heteroplasmy. Little is known about the circumstances or selection pressures involved, but there is a hint that some sort of selection for the fittest mitochondria might take place in the flight muscles themselves.

We have brought mitochondrial heteroplasmy upon ourselves in some assisted reproductive technologies, especially ooplasmic transfer. This technique involves the injection of cytoplasm, along with its mitochondria, from a healthy donor egg into the egg cell of an infertile woman, thereby mixing mitochondria from two different women. We touched on this technique in the Introduction, for it found fame in a newspaper under the headline ‘Babies born with two mothers and one father.’ More than thirty apparently healthy babies have been born by this method, despite the pungent criticism that it ‘may be akin to trying to improve a bottle of spoiled milk by adding a cup of fresh.’ The profound disquiet felt about mixing two mitochondrial populations, which nature strives so hard to avoid, combined with the suspiciously high rate of developmental abnormalities leading to miscarriage, has led to the technique being placed on hold in the United States. Even so, to an open-minded sceptic, perhaps the most surprising finding is that it works at all. Certainly heteroplasmy is worrying, probably weakening, but not out of the question.

If, as we have seen, the deepest distinction between the sexes relates to restricting the germ-line passage of mitochondria, then the barrier between the sexes seems curiously shaky. The language one tends to read in journals or books speaks of outright conflict, along the lines of: ‘organelles from more than one parent are not tolerated in the offspring.’ In more mundane reality, the condition that forces nature to differentiate two sexes, obliging us to mate with only half the population, is constantly collapsing and reforming. Mitochondrial heteroplasmy seems to be tolerated with surprisingly few detrimental effects in
many cases—there is little sign of conflict. So while the evidence suggests that mitochondria really are central to the evolution of two sexes, genomic conflict may not be all there is to it. Recent research suggests that there are other, more subtle, but probably more pervasive and fundamental reasons, too.

The area of research forcing this new thinking, ironically, is another field altogether: the study of human prehistory and population movements, by tracking human mitochondrial genes. Some of the most arresting insights into prehistory, such as our relationship with the Neanderthals, have derived from such studies of mitochondrial DNA. All these studies rest on the assumption that the inheritance of mitochondrial DNA is strictly maternal, that any mixing is simply not tolerated. In this hotbed of research, controversial data have recently raised questions about the validity of this assumption in our own case. But if some of the once iron-cast conclusions now look a bit more rickety, they do give a new insight not just into the origin of the sexes, but also into previously unexplained aspects of infertility. In the next two chapters, we’ll find out why.

In 1987, Rebecca Cann, Mark Stoneking, and Allan Wilson, at Berkeley, published a celebrated paper in
Nature
, which (although it built on earlier work) was to revolutionize our understanding of our own past. Instead of looking to the fossil record, or to genes in the nucleus, they studied the mitochondrial DNA of 147 living people, drawn from five geographical populations. They concluded that the samples were closely related, and ultimately inherited from a single woman, who lived in Africa about 200 000 years ago. She became known as ‘African Eve’, or ‘Mitochondrial Eve’, and to the best of our knowledge everyone on earth today descends from her.

The radical nature of this conclusion needs to be placed in perspective. There has long been an unresolved controversy between two warring tribes of palaeoanthropologists—those who believe that modern man issued from Africa in the fairly recent past, displacing earlier groups of migrants, like the Neanderthals and
Homo erectus
; and those who believe that humans have been present in Asia as well as Africa for at least a million years. If this latter view is correct, then the evolutionary transition from archaic to anatomically modern humans must have happened in parallel in different parts of the old world.

These two views carry a potent political charge. If all modern humans came from Africa less than 200 000 years ago, then we are all the same under the skin. We have barely had time, in an evolutionary sense, to diverge, but we can perhaps be held responsible for the extinction of our closest relatives, such as the Neanderthals. This theory is known as the ‘Out of Africa’ hypothesis. On the other hand, if the human races evolved in parallel then the differences between us are not skin deep, and our unique racial and cultural identities are firmly grounded in biology, challenging our ideals of equality. Both scenarios could have been offset by interbreeding, to an unknown degree. The dilemma is exemplified by the fate of the Neanderthals. Were they a separate subspecies driven to extinction, or did they interbreed with anatomically modern Cro-Magnons, who arrived in Europe around 40 000 years ago? Bluntly, are we
guilty of genocide or gratuitous sex? Today we seem distressingly capable of both, sometimes simultaneously.

The patchy fossil record has so far proved inconclusive, not least because it is extremely difficult to tell from a few scattered fossils of widely differing ages whether one population gives rise to another in the same place, or falls extinct, or is displaced by another from a different geographical region, or indeed whether two populations interbred. Numerous fossil finds over the last century—a train of missing links—have demonstrated the possible outlines of human evolution from ape-like ancestors, to all but the most unbelieving of Creationists. Brain size, for example, more than tripled in successive hominid fossils over the last four million years. But the actual line of evolution from Australopithecines, like Lucy, around three million years ago, through
Homo erectus
, and finally to
Homo sapiens
, is fraught with unresolved issues. How can we tell if a fossil discovery represents our own ancestors, or is simply a parallel species, now fallen extinct? Was Lucy really our direct ancestor, or just an extinct, upright, knuckle-dragging ape? All we can say for sure is that there are plenty of skeletons in the closet that exhibit morphologies intermediate between the apes and humans, even if it is difficult to assign their place in our own ancestry. Charting prehistory from ancient skeletal morphology alone is at best an uncertain endeavour.

In terms of our more recent ancestry, the fossil record is also dumb. Did we interbreed with the Neanderthals? If so, we might hope one day to discover a hybrid skeleton, displaying a mosaic of features intermediate between the robust Neanderthal Man and the gracile
Homo sapiens
. Occasionally such claims are made, but rarely convince the field. Here is the kindly Ian Tattersall, commenting on one such case: ‘the analysis… is a brave and imaginative interpretation, but it is unlikely that a majority of palaeoanthropologists will consider the case proven.’

One of the biggest problems of palaeoanthropology is its heavy reliance on morphology. This is inevitable, as little else remains. Isolating DNA would be a big help, but in most cases this is impossible. In virtually all fossil skeletons, the DNA slowly oxidizes, and very little survives beyond about 60 000 years. Even in more recent skeletons, the quantities of nuclear DNA that can be extracted are so small that sequencing is unreliable. Thus at present it seems virtually impossible to resolve our past from the fossil record alone.

Luckily, we don’t necessarily need to. In principle, we can search within ourselves to read the past. All genes accumulate mutations over time, and as they do so their sequence of ‘letters’ slowly diverges. The longer that two groups have diverged, the more differences accumulate in the sequences of their genes. Thus, if we compare the DNA sequences of a group of people, we can calculate roughly how closely related they are, at least relative to one another. People with just a few sequence differences are more closely related
than people with lots of them. By the 1970s, geneticists were becoming involved in human population studies, scrutinizing the differences between genes in different races. The results implied that there is less variation between races than had been thought—as a rule of thumb, there is more variation within races than there is between races, implying that we all share a relatively recent common ancestor. Moreover, the deepest divergences are found in sub-Saharan Africa, implying that the last common ancestor of all human races was indeed African, and lived relatively recently, certainly less than a million years ago.

Unfortunately, there are various drawbacks to this approach. Genes in the nucleus accumulate mutations very slowly, over millions of years, and indeed we still share 95 to 99 per cent of our DNA sequence with chimpanzees (depending on whether we include non-coding DNA in the sequence comparison). If gene sequences can barely tell the difference between humans and chimpanzees, then clearly we need a more sensitive measure to distinguish between human races. Another problem with gene sequences is the role of natural selection. To what extent are genes free to diverge from each other at a steady pace (neutral evolutionary drift), and when does selection constrain the rate of change, by favouring particular sequences? The answer depends not just on the gene, but also on the shifting interactions of genes with each other, and with environmental factors like climate changes, diet, infection, and migration. There is rarely an easy answer.

But the greatest problem with genes from the nucleus is sex—again. Sex recombines genes from different sources, making each of us genetically unique (apart from identical twins and clones). This in turn makes it difficult to determine our lineage. In society, the only way we can know whether we are descended from William the Conqueror, or Noah, or Ghengis Khan, is by keeping detailed records. A surname provides some indication of descent, but most genes know nothing of surnames. They could come from virtually anywhere, and any two different genes almost certainly came from two different ancestors. We are back to the problem of
The Selfish Gene
, discussed in
Part 5
—in a sexually reproducing species, individuals are fleeting and transitory, mere wisps of cloud; only the genes persist. So we can work out the history of genes, and gene frequencies in a population, but it is difficult to ascribe individual ancestry, and even harder to specify dates.

This is where Cann, Stoneking, and Wilson stepped in with their study of mitochondrial DNA, nearly two decades ago. They pointed out that the odd mode of mitochondrial inheritance solved many of the problems associated with
nuclear genes. The differences made it possible not only to trace human lineages, but also to give a tentative estimate of dates.

The first critical difference between mitochondrial and nuclear DNA is the mutation rate. On average, the mutation rate of mitochondrial DNA is nearly twenty times faster than nuclear DNA, although the actual rate varies according to the genes sampled. This fast mutation rate equates to a fast rate of evolution (but we should beware of always equating the two, as we’ll see later). The fast rate of evolution stems from the proximity of mitochondrial DNA to the free radicals generated in cellular respiration. The effect is to magnify the differences between races. While nuclear DNA can barely distinguish between chimps and humans, the mitochondrial clock ticks fast enough to reveal differences accumulating over tens of thousands of years, just the right speed for peering into human prehistory.

The second difference, said Cann, Stoneking, and Wilson, is that human mitochondrial DNA is inherited only from our mothers, by asexual reproduction. Because all our mitochondrial DNA comes from the same egg, and is replicated clonally during embryonic development, and throughout our lives, it is all (in theory) exactly the same. This means that if we take a sample of mitochondrial DNA from, say, our liver, it should be the exactly the same as a sample taken from the bone, and both should be exactly the same as a random sample taken from our mother—and hers should be exactly the same as her own mother’s, and so on back into the mists of time. In other words, mitochondrial DNA works like a matriarchal surname, linking a string of individuals together down the corridor of the centuries. Unlike nuclear genes, which are shuffled and redealt every generation, mitochondrial genes allow us to track the fate of individuals and their descendents.