The Vital Question: Why is life the way it is?

by Nick Lane

And then came the first of three major revolutions that have wracked our view of life in the past half century. This first was instigated by Lynn Margulis in the summer of love, 1967.

These ideas trace their roots to the early twentieth century, and are reminiscent of plate tectonics. It ‘looks’ as if Africa and South America were once joined together, and later pulled apart, but this childlike notion was long ridiculed as absurd. Likewise, some of the structures inside complex cells look like bacteria, and even give the impression of growing and dividing independently. Perhaps the explanation really was as simple as that – they are bacteria!

This Margulis did for two specialised structures inside cells – the mitochondria, seats of respiration, in which food is burned in oxygen to provide the energy needed for living, and the chloroplasts, the engines of photosynthesis in plants, which convert solar power into chemical energy. Both of these ‘organelles’ (literally miniature organs) retain tiny specialised genomes of their own,

Revolution number two was the phylogenetic revolution – the ancestry of genes.

Woese chose one of the subunits from the ribosome, a single machine part, so to speak, and compared its sequence across different species, from bacteria such as E. coli to yeast to humans. His findings were a revelation, and turned our world view on its head. He could distinguish between the bacteria and complex eukaryotes without any difficulty, laying out the branching tree of genetic relatedness within and between each of these magisterial groups. The only surprise in this was how little difference there is between plants and animals and fungi, the groups that most biologists have spent most of their lives studying. What nobody anticipated was the existence of a third domain of life.

Over the last few years, comparisons of large numbers of genes in more representative samples of species have come to the unequivocal conclusion that the host cell was in fact an archaeon – a cell from the domain Archaea. All archaea are prokaryotes. By definition, they don’t have a nucleus or sex or any of the other traits of complex life, including phagocytosis. In terms of its morphological complexity, the host cell must have had next to nothing. Then, somehow, it acquired the bacteria that went on to become mitochondria. Only then did it evolve all those complex traits. If so, the singular origin of complex life might have depended on the acquisition of mitochondria. They somehow triggered it. This radical proposition – complex life arose from a singular endosymbiosis between an archaeon host cell and the bacteria that became mitochondria – was predicted by the brilliantly intuitive and free-thinking evolutionary biologist Bill Martin, in 1998, on the basis of the extraordinary mosaic of genes in eukaryotic cells, a mosaic largely uncovered by Martin himself.

Martin predicted that complex life arose through a singular endosymbiosis between two cells only. He predicted that the host cell was an archaeon, lacking the baroque complexity of eukaryotic cells. He predicted that there never was an intermediate, simple eukaryotic cell, which lacked mitochondria; the acquisition of mitochondria and the origin of complex life was one and the same event. And he predicted that all the elaborate traits of complex cells, from the nucleus to sex to phagocytosis, evolved after the acquisition of mitochondria, in the context of that unique endosymbiosis. This is one of the finest insights in evolutionary biology, and deserves to be much better known. It would be, were it not so easily confounded with the serial endo-symbiosis theory (which we’ll see makes none of the same predictions). All of these explicit predictions have been borne out in full by genomic research over the past two decades. It’s a monument to the power of biochemical logic.

We know that complex cells arose on just one occasion in 4 billion years of evolution, through a singular endosymbiosis between an archaeon and a bacterium

Essentially all living cells power themselves through the flow of protons (positively charged hydrogen atoms), in what amounts to a kind of electricity – proticity – with protons in place of electrons. The energy we gain from burning food in respiration is used to pump protons across a membrane, forming a reservoir on one side of the membrane. The flow of protons back from this reservoir can be used to power work in the same way as a turbine in a hydroelectric dam. The use of cross-membrane proton gradients to power cells was utterly unanticipated. First proposed in 1961 and developed over the ensuing three decades by one of the most original scientists of the twentieth century, Peter Mitchell, this conception has been called the most counterintuitive idea in biology since Darwin, and the only one that compares with the ideas of Einstein, Heisenberg and Schrödinger in physics.

So it seems to me there are two big unknowns at the very heart of biology today: why life evolved in the perplexing way it did, and why cells are powered in such a peculiar fashion. This book is an attempt to answer these questions, which I believe are tightly entwined.

I hope to persuade you that energy is central to evolution, that we can only understand the properties of life if we bring energy into the equation. I want to show you that this relationship between energy and life goes right back to the beginning – that the fundamental properties of life necessarily emerged from the disequilibrium of a restless planet. I want to show you that the origin of life was driven by energy flux, that proton gradients were central to the emergence of cells, and that their use constrained the structure of both bacteria and archaea. I want to demonstrate that these constraints dominated the later evolution of cells, keeping the bacteria and archaea forever simple in morphology, despite their biochemical virtuosity. I want to prove that a rare event, an endosymbiosis in which one bacterium got inside an archaeon, broke those constraints, enabling the evolution of vastly more complex cells. I want to show you that this was not easy – that the intimate relationship between cells living one inside another explains why morphologically complex organisms only arose once. I hope to do more, to persuade you that this intimate relationship actually predicts some of the properties of complex cells. These traits include the nucleus, sex, two sexes, and even the distinction between the immortal germline and the mortal body – the origins of a finite lifespan and genetically predetermined death. Finally, I want to convince you that thinking in these energetic term...

Onions, wheat and amoebae have more genes and more DNA than we do. Amphibians such as frogs and salamanders have genome sizes that range over two orders of magnitude, with some salamander genomes being 40 times larger than our own, and some frogs being less than a third of our size. If we had to sum up the architectural constraints on genomes in a single phrase, it would have to be ‘anything goes’.

Genomes do not predict the future but recall the past: they reflect the exigencies of history.

A brief history of the first 2 billion years of life

I shall argue that the distinction between a ‘living planet’ – one that is geologically active – and a living cell is only a matter of definition. There is no hard and fast dividing line. Geochemistry gives rise seamlessly to biochemistry. From this point of view, the fact that we can’t distinguish between geology and biology in these old rocks is fitting. Here is a living planet giving rise to life, and the two can’t be separated without splitting a continuum.

We tend to think of bacteria and minerals as occupying different realms, living versus inanimate, but in fact many sedimentary rocks are deposited, on a colossal scale, by bacterial processes.

In all forms of photosynthesis, the energy of light is used to strip electrons from an unwilling donor. The electrons are then forced on to carbon dioxide to form organic molecules. The various forms of photosynthesis differ in their source of electrons, which can come from all kinds of different places, most commonly dissolved (ferrous) iron, hydrogen sulphide, or water. In each case, electrons are transferred to carbon dioxide, leaving behind the waste: rusty iron deposits, elemental sulphur (brimstone) and oxygen, respectively.

First, life arose very early, probably between 3.5 and 4 billion years ago, if not earlier, on a water world not unlike our own. Second, by 3.5 to 3.2 billion years ago, bacteria had already invented most forms of metabolism, including multiple forms of respiration and photosynthesis.

The Great Oxidation Event has long been recognised as a pivotal moment in the history of our living planet, but its significance has shifted radically in recent years, and the new interpretation is critical to my argument in this book. The old version sees oxygen as the critical environmental determinant of life.

All plants, animals, algae, fungi and protists share a common ancestor – the eukaryotes are monophyletic. This means that plants did not evolve from one type of bacteria, and animals or fungi from other types. On the contrary, a population of morphologically complex eukaryotic cells arose on a single occasion – and all plants, animals, algae and fungi evolved from this founder population. Any common ancestor is by definition a singular entity – not a single cell, but a single population of essentially identical cells. That does not in itself mean that the origin of complex cells was a rare event. In principle, complex cells could have arisen on numerous occasions, but only one group persisted – all the rest died out for some reason. I shall argue that this was not the case, but first we must consider the properties of eukaryotes in a little more detail.

So what does phylogenetics tell us was part of the common ancestor? Shockingly, nearly everything else. Let me run through a few items.

Selection of the best-adapted traits means loss of the less well-adapted traits, so selection continuously eliminates intermediates. Over time, traits will tend to scale the peaks of an adaptive landscape,

so we see the apparent perfection of eyes, but not the less perfect intermediate steps en route to their evolution. In The Origin of Species Darwin made the point that natural selection actually predicts that intermediates should be lost. In that context, it is not terribly surprising that there are no surviving intermediates between bacteria and eukaryotes. What is more surprising, though, is that the same traits do not keep on arising, time and time again – like eyes.

So powered flight arose on at least six different occasions in bats, birds, pterosaurs and various insects; multicellularity about 30 times, as noted earlier; different forms of endothermy (warm blood) in several groups including mammals and birds,

but also some fish, insects and plants;6 and even conscious awareness appears to have arisen more or less independently in birds and mammals. As with eyes, we see a myriad of different forms reflecting the different environments in which they arose.

More significantly, there is very strong evidence that the intermediates were not, in fact, outcompeted to extinction by more sophisticated eukaryotes. They still exist. We met them already – the ‘archezoa’, that large group of primitive eukaryotes that were once mistaken for a missing link. They are not true evolutionary intermediates, but they’re real ecological intermediates. They occupy the same niche.

Why would a virus not be alive? Because it does not have any active metabolism of its own; it relies entirely on the power of its host.

Plainly there is a continuum between non-living and living, and it is pointless to try to draw a line across it. Most definitions of life focus on the living organism itself, and tend to ignore life’s parasitising of its environment.

In terms of overall entropy, then, and taking all these physical interactions into consideration, an ordered oily membrane around a cell is a higher entropy state than a random mixture of immiscible molecules, even though it looks more ordered.2 Grind up a spore and the overall entropy hardly changes, because although the crushed spore itself is more disordered, the component parts now have a higher energy than they did before – oils are mixed with water, immiscible proteins are rammed hard together.

The membrane is organised as a bilayer, with hydrophilic heads interacting with the watery contents of the cytoplasm and the surroundings, and the hydrophobic tails pointing inwards and interacting with each other. This is a low-energy, physically ‘comfortable’ state: despite its ordered appearance, the formation of lipid bilayers actually increases overall entropy by releasing energy as heat into the surroundings.

To understand this, remember that the second law says, "the total, overall entropy of a set of participating systems always increases."

When all this is taken into consideration in the case of the spore, the overall entropy barely changes.

a reaction will take place on its own accord only if G is negative. For that to be the case, either the entropy of the system must rise (the system becomes more disordered) or energy must be

lost from the system as heat, or both. This means that local entropy can decrease – the system can become more ordered – so long as H is even more negative, meaning that a lot of heat is released to the surroundings. The bottom line is that, to drive growth and reproduction – living! – some reaction must continuously release heat into the surroundings, making them more disordered.

Just think of the stars. They pay for their ordered existence by releasing vast amounts of energy into the universe. In our own case, we pay for our continued existence by releasing heat from the unceasing reaction that is respiration. We are continuously burning food in oxygen, releasing heat into the environment. That heat loss is not waste – it is strictl...

a total turnover of ATP of around 60–100 kilograms per day – roughly our own body weight. In fact, we contain only about 60 grams of ATP, so we know that every molecule of ATP is recharged once or twice a minute.

The endless cycle is as simple as this: ADP + Pi + energy ATP

Convert these numbers into power measured in watts and they are just as incredible. We use about 2 milliwatts of energy per gram – or some 130 watts for an average person weighing 65 kg, a bit more than a standard 100 watt light bulb. That may not sound like a lot, but per gram it is

a factor of 10,000 more than the sun (only a tiny fraction of which, at any one moment, is undergoing nuclear fusion). Life is not much like a candle; more of a rocket launcher.

There are two aspects to the energy of life that are unexpected. First, all cells derive their energy from just one particular type of chemical reaction known as a redox reaction, in which electrons are transferred from one molecule to another.

respiration and burning are equivalent; the slight delay in the middle is what we know as life.

The second unexpected aspect to the energy of life is the detailed mechanism by which energy is conserved in the bonds of ATP.

For every ten protons that pass through the ATP synthase, the rotating head makes one complete turn, and three newly minted ATP molecules are released into the matrix.

So why does life on earth use redox chemistry?

I imagine CO2 as a kind of a Lego brick. It can be plucked from the air and added one carbon at a time on to other molecules. Silicon oxides in contrast … well, you try building with sand. Silicon or other elements might be amenable to use by a higher intelligence such as ourselves, but it is hard to see how life could have bootstrapped itself from the bottom up using silicon. That’s not to say that silicon-based life couldn’t possibly evolve in an infinite universe, who could say; but as a matter of probability and predictability, which is what this book is about, that seems overwhelmingly less likely.

Consider the problem the other way around: what is good about the redox chemistry of respiration? Plenty, it seems. When I say respiration, we need to look beyond ourselves. We strip electrons from food and transfer them down our respiratory chains to oxygen, but the critical point here is that the source and the sink of electrons can both be changed.

Because these proteins are plugged into a common operating system, they can be mixed and matched to fit any environment. They are not only interchangeable in principle, but in practice they’re passed around with abandon.

Genes encoding respiratory proteins are among those most commonly swapped by lateral transfer. Together, they comprise what biochemist Wolfgang Nitschke calls the ‘redox protein construction kit’. Did you just move to an environment where hydrogen sulphide and oxygen are both common, such as a deep-sea vent? No problem, help yourself to the requisite genes, they’ll work just fine for you, sir. You’ve run out of oxygen? Try nitrite, ma’am! Don’t worry. Take a copy of nitrite reductase and plug it in, you’ll be fine!

the cell membranes – strictly necessary for chemiosmotic coupling, otherwise known as membrane bioenergetics – are biochemically different in bacteria and archaea.

Membrane bioenergetics are universal – but membranes are not. One might imagine that the last common ancestor had a bacterial-type membrane, and that archaea replaced it for some adaptive reason, perhaps because archaeal membranes are better at higher temperatures. That is superficially plausible, but there are two big problems. First, most archaea are not hyperthermophiles;

If it is possible to switch membranes, then why don’t we see the wholesale replacement of membrane lipids on other occasions, as cells adapt to new environments?