Vital Question: Energy, Evolution, and the Origins of Complex Life

by Nick Lane

Life, as biochemist Albert Szent-Györgyi observed, is nothing but an electron looking for a place to rest.

The killer fact that emerges from this enormous diversity is how damned similar eukaryotic cells are. We do not find all kinds of intermediates and unrelated variants. The prediction of the serial endosymbiosis theory, that we should, is wrong.

The eukaryotic common ancestor might as well have jumped, fully formed, like Athena from the head of Zeus. We gain little insight into traits that arose before the common ancestor – essentially all of them. How and why did the nucleus evolve? What about sex? Why do virtually all eukaryotes have two sexes? Where did the extravagant internal membranes come from? How did the cytoskeleton become so dynamic and flexible? Why does sexual cell division (‘meiosis’) halve chromosome numbers by first doubling them up? Why do we age, get cancer, and die? For all its ingenuity, phylogenetics can tell us little about these central questions in biology. Almost all the genes involved (encoding so-called eukaryotic ‘signature proteins’) are not found in prokaryotes. And conversely, bacteria show practically no tendency to evolve any of these complex eukaryotic traits. There are no known evolutionary intermediates between the morphologically simple state of all prokaryotes and the disturbingly complex common ancestor of eukaryotes (Figure 6). All these attributes of complex life arose in a phylogenetic void, a black hole at the heart of biology.

For now, though, let’s just note that some sort of structural constraint must have acted equally on both of the two great domains of prokaryotes, the bacteria and archaea, forcing both groups to remain simple in their morphology throughout an incomprehensible 4 billion years. Only eukaryotes explored the realm of complexity, and they did so via an explosive monophyletic radiation that implies a release from whatever these structural constraints might have been. That appears to have happened just once – all eukaryotes are related.

any proper account must explain why the evolution of complex life happened only once: our explanation must be persuasive enough to be believable, but not so persuasive that we are left wondering why it did not happen on many occasions.

Any attempt to explain a singular event will always have the appearance of a fluke about it. How can we prove it one way or another? There might not be much to go on in the event itself, but there may be clues concealed in the aftermath, a smoking gun that gives some indication of what happened. Once they cast off their bacterial shackles, the eukaryotes became enormously complex and diverse in their morphology. Yet they did not accrue this complexity in an obviously predictable way: they came up with

a whole series of traits, from sex and ageing to speciation, none of which have ever been seen in bacteria or archaea. The earliest eukaryotes accumulated all these singular traits in a common ancestor without peer. There are no known evolutionary intermediates between the morphological simplicity of bacteria and that enormously complex eukaryotic common ancestor to tell the tale. All of this adds up to a thrilling prospect – the biggest questions in biology r...

Life could have been driven by thermal or mechanical energy, or radioactivity, or electrical discharges, or UV radiation, the imagination is the limit; but no, all life is driven by redox chemistry, via remarkably similar respiratory chains.

The question boils down to two parts: why do all living cells use redox chemistry as a source of free energy? And why do all cells conserve this energy in the form of proton gradients over membranes? At a more fundamental level, these questions are: why electrons, and why protons?

I closed the first chapter with some big questions about the evolution of life on earth. Why did life arise so early? Why did it stagnate in morphological complexity for several billion years? Why did complex, eukaryotic, cells arise just once in 4 billion years? Why do all eukaryotes share a number of perplexing traits that are never found in bacteria or archaea, from sex and two sexes to ageing? Here I am adding two more questions of an equally unsettling magnitude: why does all life conserve energy in the form of proton gradients across membranes? And how (and when) did this peculiar but fundamental process evolve?

I think the two sets of questions are linked. In this book, I will argue that natural proton gradients drove the origin of life on earth in a very particular environment, but an environment that is almost certainly ubiquitous across the cosmos: the shopping list is just rock, water and CO2.

I will argue that chemiosmotic coupling constrained the evolution of life on earth to the complexity of bacteria and archaea for billions of years. A singular event, in which one bacterium somehow got inside another one, overcame these endless energetic constraints on bacteria. That endosymbiosis gave rise to eukaryotes with genomes that swelled over orders of magnitude, the raw material for morphological complexity. The intimate relationship between the host cell and its endosymbionts (which went on to become mitochondria) was, I shall argue, behind many strange properties shared by eukaryotes. Evolution should tend to play out along similar lines, guided by similar constraints, elsewhere in the universe. If I am right (and I don’t for a moment think I will be in all the details, but I hope that the bigger p...

All living organisms are sustained by far-from-equilibrium conditions in their environment: we, too, are dissipative structures. The continuous reaction of respiration provides the free energy that cells

need to fix carbon, to grow, to form reactive intermediates, to join these building blocks together into long-chain polymers such as carbohydrates, RNA, DNA and proteins, and to maintain their low-entropy state by increasing the entropy of the surroundings.

In the absence of genes or information, certain cell structures, such as membranes and polypeptides, should form spontaneously, so long as there is a continuous supply of reactive precursors – activated amino acids, nucleotides, fatty acids; so long as there is a continuous flux of energy providing the requisite building blocks. Cell structures are forced into existence by the flux of energy and matter. The parts can be replaced but the structure is stable and will persist for as long as the flux persists. This continuous flux of energy and matter is precisely what is missing from the primordial soup. There is nothing in soup that can drive the formation of t...

The geochemists Jan Amend and Tom McCollom have gone even further and calculated that the formation of organic matter

from H2 and CO2 is thermodynamically favoured under alkaline hydrothermal conditions, so long as oxygen is excluded. That’s remarkable. Under these conditions, between 25 and 125°C, the formation of total cell biomass (amino acids, fatty acids, carbohydrates, nucleotides and so on) from H2 and CO2 is actually exergonic. This means that organic matter should form spontaneously from H2 and CO2 under these conditions. The formation of cells releases energy and increases overall entropy!

Now cells had evolved active ion pumps and modern membranes, and were finally free to leave the vents, escaping into the open oceans. From a common ancestor that lived from proton gradients in vents, the first free-living cells, bacteria and archaea, emerged independently. It’s not surprising that bacteria and archaea should have come up with distinct cell walls to protect them against these new shocks, nor indeed that they should have ‘invented’ DNA replication independently. Bacteria attach their DNA to the cell membrane during cell division, at a site called the replicon; the attachment enables each daughter cell to receive a copy of the genome. The molecular machinery required to attach DNA to the membrane, and many details of DNA replication, must depend at least partly on the mechanics of that attachment. The fact that cell membranes evolved independently begins to explain why DNA replication should be so different in bacteria and archaea. Much the same applies to cell walls, all the components of which must be exported from inside the cell through specific membrane pores – hence the synthesis of the cell wall depends on the properties of the membrane, and should differ in bacteria and archaea.

And so we draw to a close. While bioenergetics do not predict from first principles that there should be fundamental differences between bacteria and archaea, these considerations do explain how and why they could have arisen in the first place. The deep differences between the prokaryotic domains had nothing to do with adaptation to extreme environments, such as high temperatures, but rather the divergence of cells with membranes that were obliged to remain leaky for bioenergetic reasons. While the divergence of archaea and bacteria might not be predictable from first principles, the fact that both groups are chemiosmotic (depending on proton gradients across membranes) does follow from the physical principles discussed in these last two chapters. The environment most realistically capable of giving rise to life, whether here or anywhere else in the universe, is alkaline hydrothermal vents. Such vents constrain cells to make use of natural proton gradients, and ultimately to generate their own. In this context it’s no mystery that all cells here on earth should be chemiosmotic. I would expect that cells across the universe will be chemiosmotic too. And that means they will face exactly the same problems that life on earth does. In the next part, we’ll see why this universal requirement for proton power predicts that complex life will be rare in the universe.

In the broadest of terms, prokaryotes explored the possibilities of metabolism, finding ingenious solutions to the most arcane chemical challenges, while eukaryotes turned their back on this chemical cleverness, and explored instead the untapped potential of larger size and greater structural complexity.

If the eukaryotes arose in an endosymbiosis between two prokaryotes, an archaeal host cell and a bacterial endosymbiont, which went on to become mitochondria, then we can explore the question from a more conceptual point of view. Can we think of a good reason why one cell getting inside another cell should transform the prospects of prokaryotes, unleashing the potential of eukaryotic complexity? Yes. There is a compelling reason, and it relates to energy.

After weeks of talking, trading ideas and perspectives, it suddenly dawned on us that the key to the evolution of eukaryotes lies in the simple idea of ‘energy per gene’.

Bacteria can’t expand their genome size, nor can they accumulate the thousands of new gene families, encoding all kinds of new functions, that epitomise eukaryotes. Rather than evolving a single gigantic nuclear genome, they end up hoarding thousands of copies of their standard-issue small bacterial genome.

How could an error catastrophe be averted? Simply by inserting a barrier in the way, according to Martin and Koonin. The nuclear membrane is a barrier separating transcription from translation – inside the nucleus, genes are transcribed into RNA codescripts; outside the nucleus, the RNAs are translated into proteins on the ribosomes. Crucially, the slow process of splicing takes place inside the nucleus, before the ribosomes can get anywhere near the RNA. That is the whole point of the nucleus: to keep ribosomes at bay. This explains why eukaryotes need a nucleus but prokaryotes don’t – prokaryotes don’t have an intron problem.

The beginning was a pile of lipid bags surrounding a genome; the end point was the nuclear membrane, replete with its sophisticated pores.

Organisms that inherit the new mutation dominate, and the gene ultimately spreads to ‘fixation’: all organisms in the population end up with a copy of the gene. But natural selection can only ‘see’ the whole chromosome. This means that the other 99 genes on the chromosome also become fixed in the population – they go along for the ride and are said to ‘hitch-hike’ to fixation. This is a disaster.

By generating chromosomes with different combinations of alleles – ‘fluid chromosomes’ – sex allows selection to act on all genes individually. Selection, like God, can now see all our vices and virtues, gene by gene. That’s the great advantage of sex.

The puzzle is that sex is ubiquitous among eukaryotes. One might think that the advantages would offset the costs under certain circumstances but not others. To a point this is true, in that microbes may divide asexually for 30 generations or so, before indulging in occasional sex, typically when in a state of stress. But sex is far more widespread than seems reasonable. This is probably because the last common ancestor of eukaryotes was already sexual, and hence all her descendants were sexual too. While many microorganisms no longer have regular sex, very few ever lost sex altogether without falling extinct. The costs of never having sex are therefore high. A similar argument should apply to the earliest eukaryotes. Those that never had sex – arguably all those that had not ‘invented’ sex – were likely to fall extinct.

Of course, the removal of cells that don’t work well enough only improves overall tissue function if they are replaced with new cells from the stem-cell population. A major problem with neurons and muscle cells is that they cannot be replaced. How could a neuron be replaced? Our life’s experience is written into synaptic networks, each neuron forming as many as 10,000 different synapses. If the neuron dies by apoptosis, those synaptic connections are lost forever, along with all the experience and personality that might have been written into them. That neuron is irreplaceable. In fact, while less obviously necessary, all terminally differentiated tissues are irreplaceable – their very existence is impossible without the deep distinction between germline and soma discussed in the previous chapter. Selection is all about offspring. If organisms with large and irreplaceable brains leave more viable offspring than organisms with small replaceable brains, then they will thrive. Only when there is a distinction between the germline and soma can selection act in this way; but when it does, the body becomes disposable. Lifespan becomes finite. And cells that can’t meet their metabolic requirements will kill us in the end.

The cost of high aerobic capacity is low fertility. More embryos that could have survived some lesser purpose must be sacrificed on the altar of perfection.

There are costs and benefits to both sides. A low threshold gives a high aerobic fitness and a low risk of disease, but at the cost of a high rate of infertility and poor adaptability. A high threshold gives a low aerobic capacity and higher risk of disease but with the benefits of greater fertility and better adaptability. These are words to conjure with. Fertility. Adaptability. Aerobic fitness. Disease. We can’t cut much closer to the grain of natural selection than that. I reiterate: all these trade-offs emerge inexorably from the requirement for two genomes.