First steps to the individual

This view is entirely compatible with the hydrogen hypothesis, for it implies that the cells involved in the initial eukaryotic merger lived peacefully together, but nonetheless retained their own interests. These interests stretched to manipulating the host for sex, in the case of mitochondria, but not to murder, from which neither side could gain. Moreover, such a gently manipulative relationship, in which most interests are aligned at most times, explains why the machinery of apoptosis might have survived in single cells for possibly hundreds of millions of years—sex benefits both the damaged host and the mitochondria, and so would not be penalized by natural selection.

But the question remains: how did sex turn into death? We know that the mitochondria brought most of the death machinery with them, and they certainly use it to kill their hosts by apoptosis today. If we accept that the original purpose of the death machinery was sex, not death, what led to such a portentous change in purpose? When did the drive for sex become punishable by death, and why?

Sex and death are entwined. To an extent, both serve the same purpose.

Consider why yeasts and Volvox are driven to recombine their genes when their DNA is damaged: recombination of genes probably enables the damaged copy to be replaced, or masked, by an undamaged copy of the same gene. Similarly, free radicals promote lateral gene transfer in bacteria (the uptake of genes from other cells or the environment). Again, the damaged genes are replaced or masked. What of programmed cell death, then? In multicellular organisms, apoptosis is also a means of repairing damage. Rather than the costly option of fixing a broken cell, apoptosis takes the cost-effective approach of eliminating it from the body, making space for an undamaged replacement—the first steps towards our modern 'throwaway' culture. So sex helps to eliminate damaged genes, while apoptosis eliminates damaged cells. Seen from the point of view of the 'higher' organism, sex repairs damaged cells and apoptosis repairs damaged bodies.

In Blackstone's view, the machinery of apoptosis originally signalled cells to fuse, instigating recombination and repair of damage. At a later stage, in multi-cellular organisms, the machinery was rededicated to death. In principle, all that was required was the insertion of a new step—the caspase cascade. We noted earlier that the caspase enzymes were inherited from a-proteobacteria (probably by way of the mitochondrial merger), but that they serve a different purpose in bacteria—they slice up some proteins, but do not bring about the death of the cell. In this respect, it's interesting that different groups of eukary-otes appear to have integrated the caspase enzymes into programmed cell death quite independently. Plants, for example, bring about cell death using a group of related proteins known as meta-caspases, whereas mammals use the familiar caspase cascade. Both, however, trigger cell death through the release of cytochrome c and other proteins from the mitochondria. This implies that the death machinery of apoptosis arose independently more than once in the eukaryotes, in response to a common signal (free radicals, and the release of proteins from stressed mitochondria) and a common selection pressure—the need to eliminate damaged cells from a multicellular organism.

If apoptosis is linked with the need to police the multicellular state, rather than a parasite war, and multicellular organisms evolved independently more than once, which they certainly did, then it is not surprising that the detailed execution of apoptosis differs in different groups. On the face of it, it is more surprising that there is so much in common—that somewhat similar machinery was pressed into service more than once. Why was this?

Again Blackstone suggests an answer. He has spent many years studying some of the most primitive animals, such as marine colonial hydroids (colonies of cells that are capable of reproducing sexually or asexually, by fragmentation). He argues that a multicellular colony offers various advantages over individual cells, but as soon as the cells within a colony begin to differentiate—

so that some are obliged to fulfil menial tasks, like paddling (moving the colony around), while others form fruiting bodies that pass on their genes—then a tension must develop. What stops the menial 'slave' cells from revolting?

Although they are all genetically identical (for a period at least), the cells in a colony don't have equal opportunities—a 'caste' system develops in which some cells reap privilege at the expense of others. Blackstone argues that redox gradients are set up by the food and oxygen supply, which varies with currents, other local fluctuations, and the position of cells within the colony (at the surface or buried under other cells). Some cells have plenty of oxygen and food while others are deprived of one or the other, and so find themselves in a different redox state. The differentiation of cells is controlled by their redox state, by way of signals from the mitochondria. We have already noted, for example, that a lack of respiratory electrons, due to starvation, generates a signal for stress resistance.

The urge for independent sex—welling up as a burst of free radicals from the mitochondria—is also a redox signal. In a colony, damaged cells that attempt to have sex with other cells are likely to jeopardize the survival of the colony as a whole—only chaos can ensue. The very signal for sex is a confession of damage to the cell. It is as much as to say that the cell can no longer perform its normal tasks. In somatic (body) cells, there must have been a strong selection pressure to transmute a redox signal for sex into a signal for death. And in time, the selective removal of damaged cells for the greater good paved the way for the evolution of the individual, in whom common purpose is policed by apoptosis. So the cries for freedom of captive mitochondria, which may once have urged for sex in single cells, were met with death in a multicellular body—their own, along with their damaged host cells.

This answer gives a beautiful insight into the vested interests of different cells, and how these can ebb and flow over time. The final outcome may depend on the environment that the cells find themselves in. In the first eukaryotic cells, the host cells and their mitochondria each had their own selfish interests. For the most part, these interests were aligned, but that was not always the case. In particular, if a host cell became genetically damaged, in a way that prevented it from dividing, the mitochondria were effectively imprisoned, for they no longer had the autonomy to survive outside the host. Their only escape was through the act of sexual fusion, for in this way they can be passed on to another cell directly. One signal for sexual fusion in simple single-celled organisms is a burst of free radicals emanating from the mitochondria, so mitochondria can indeed manipulate their host cells in this way.

When the host cells formed into colonies, however, times changed. There are many advantages to living in primitive colonies, without the constituent cells having to give up the possibility of a return to free living. But for this reason, the path from a colony to a genuine multicellular individual is tricky. The fact that all multicellular individuals make use of apoptosis suggests that cells must accept the death penalty if they step out of line. But why did they do so? Perhaps because the damaged cells were betrayed by their own mitochondria. The free-radical signals, welling up from the mitochondria, amount to a confession of damage to the host cell. In a colony, the future of the other cells is jeopardized: the majority gain if the damaged cell is eliminated. So the battleground shifts from the mitochondria and their host cells, to the cells of the colony, and finally to the more familiar setting of competing multicellular individuals.

One question that emerges from this scenario is, how did the colony as a whole reproduce? If any cells in a colony that 'want' to have sex are eliminated, then the colony as a whole is under pressure to find a common, agreed method of reproduction. Today, individuals produce dedicated sex cells from a sequestrated germ-line that is hived off well before birth. How and why such sequestration got started is a conundrum, but if the punishment for sex was generally death, then it must have been much easier to make a single exception rather than many. Surely this must have been a strong selective pressure to sequestrate a germ-line. Such an executive decision might have had a startling outcome. Once a sequestrated germ-line had been established, then multicellular individuals could only replicate by way of sex. The individual no longer persisted from one generation to the next; no more did any of the individual cells, nor even chromosomes. Bodies dissolved and reformed like wisps of cloud, each one fleeting and different. Does this sound at all familiar? I'm repeating myself from the beginning of this Part: these conditions codified the selfish gene. Ironically, the long battles between individual cells that ultimately gave rise to the multicellular individual may in the end have crowned a different victor, who slipped in through the back door: the gene.

Primitive multicellular colonies stand at the gates of sex and death, of selfish cells and selfish genes, and it will be revealing to learn more about their behaviour. It will be revealing, too, to learn more of the mitochondrial signals for sex in single cells. For while sex looks like a good idea from the point of view of mitochondria, the fusion of two cells leads to another conflict—between the two populations of mitochondria derived from the two fusing cells. These populations are not the same, and so can compete among themselves to the detriment of the newly fused host cell. Today, sexual organisms go to extraordinary lengths to block the entry of mitochondria from one of the two parents. Indeed, at a cellular level, the inheritance of mitochondria from only one of the two parents is among the defining attributes of gender. Mitochondria might once have pushed for sex, but they left us everlastingly with two sexes.

PART 6

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