The History of Life: Genesis Revisited

From New Scientist - 28 April 2016

THE HISTORY OF LIFE

Genesis revisited

Oxygen is supposed to have driven the evolution of complex life. Great story, says biochemist Nick Lane, but it's wrong

GO WEST, young man! More specifically, go about 200 kilometres west of Crete, then straight down to the bottom of the Mediterranean Sea 3.5 kilometres below. There you will find a lake with some extraordinary inhabitants.

Around 6 million years ago when the Mediterranean nearly dried up, vast amounts of salt were deposited on the sea floor. Some of these deposits were exposed about 30,000 years ago. As this salt dissolves, extra-salty, dense water is sinking to the depths, forming a brine lake 100 metres deep. Even more surprising than the existence of this lake beneath the sea, however, is what lives in it.

The water in the brine lake does not mix with the water above and so ran out of oxygen long ago. Instead, the toxic gas hydrogen sulphide oozes from the black mud. It's the last place you would expect to find animals. But that's exactly what has been discovered: the first animals, as far as we know, that can grow and reproduce without a whiff of oxygen.

These tiny mud-dwellers are far more than a curiosity. They could be the best pointer yet to the origin of complex cells: the basis of most life on Earth, from amoebae to oak trees.

"The ecology is interesting, but the real significance of these critters is what they say about evolution," says Bill Martin, an evolutionary biologist at the University of Düsseldorf in Germany. For Martin, the discovery is a beautiful affirmation of a radical prediction he made more than a decade ago – that oxygen had nothing to do with the evolution of complex life.

The first kinds of life on Earth, the bacteria and archaea, were simple cells – not much more than bags of chemicals. Eventually, they gave rise to complex cells, or eukaryotes, with sophisticated internal structures, the kind of cells found inside all plants and animals. And one of the most important events in the evolution of complex cells was the formation of a symbiotic union between a host cell and a bacterium – the ancestor of the cellular powerhouses known as mitochondria, which extract energy from food using oxygen.

"Burning" food provides 10 times as much energy as alternative ways of extracting energy from food without oxygen. When complex cells gained this ability, it changed the course of life on Earth: without mitochondria, large active animals might never have evolved (see "Living without breathing"). It is not surprising, then, that most biologists think that the original symbiotic union revolved around oxygen. According to Martin, though, they are utterly wrong.

The narrative in the textbooks seems compelling. In the beginning, so the story goes, there was no oxygen. The evolution of photosynthesis changed all that. By releasing their waste – oxygen – into the air, cyanobacteria transformed the globe around 2.3 billion years ago. As oxygen levels rose, the toxic gas caused the first mass extinction, wiping out nearly all existing organisms and paving the way for a new lifestyle: extracting energy from food using oxygen.

The bacteria that evolved this ability were preyed on by other cells. At some point, one cell failed to digest its dinner and instead let the bacteria live on inside it. This host cell, so the story goes, got two huge benefits: protection against oxygen, which was guzzled up by the ancestral mitochondria, and a share of the extra energy its guests could extract from food using oxygen.

It was not until oxygen levels rose even higher, around half a billion years ago, that the oceans could support large multicellular organisms that got their energy by burning food. That led to the Cambrian explosion, when all kinds of animals appeared. The main point about this story is that it sweeps forward with a magisterial inevitability, waiting only on a rising tide of oxygen.

The broad outlines are true. Oxygen levels did rise in two steps; most eukaryotes do generate energy using oxygen, and are normally tolerant of its toxicity; and the earliest fossil animals did appear soon after a big rise in oxygen levels in the oceans. Yet there are grounds to suspect that oxygen was not the puppet master after all.

One is that the initial rise in oxygen did not cleanse the oceans, but converted them into a stinking mess, full of hydrogen sulphide. Far from having few refuges, anaerobes had whole oceans to themselves. What's more, these conditions lasted for more than a billion years, right through the period when the eukaryotes are thought to have evolved.

No free lunch

Another issue is that oxygen is not particularly toxic by itself – it needs to be converted into free radicals before it will react with and destroy proteins and DNA. Mitochondria generate lots of free radicals so, far from protecting their hosts from oxygen, their ancestors would have increased the damage it does. In any case, consuming oxygen merely steepens the diffusion gradient; it's like trying to save yourself from drowning by drinking the surrounding ocean.

Even the power advantage of oxygen is problematic. No bacterium gives away energy for free, so the host cell could not have benefited from oxygen respiration until it had evolved the kit needed to siphon off energy-rich ATP from its guest bacteria. In the meantime, the "symbiosis" would have been a disaster. Thanks to their ability to exploit oxygen, the bacteria would be likely to outgrow the host and end up killing it.

So if the union was not about oxygen, what was it about? Hydrogen, according to Martin and Miklos Müller of The Rockefeller University in New York.

Back in the 1970s, Müller discovered that some single-celled organisms have structures that resemble mitochondria but do something quite different; they generate energy without using oxygen, by breaking food down into carbon dioxide and hydrogen – so Müller called them hydrogenosomes.

Before hooking up with Martin, Müller had gone on to show that hydrogenosomes do not merely resemble mitochondria but are in fact stripped-down mitochondria. They have the same shell, yet completely lack the usual ATP-generating machinery driven by oxygen. Instead, they have machinery that generates ATP while creating hydrogen as waste. The question is, was this different machinery acquired as mitochondria evolved into hydrogenosomes, or was it present all along? And if it was present all along, then what did the bacterial ancestor of the mitochondria actually look like?

Martin and Müller leapt straight in at the deep end. The ancestor of mitochondria, they said, was a versatile bacterium capable of living in a variety of environments – it could use many substances, including oxygen, to produce energy, and it could make hydrogen too. This is hardly an imaginary superbug: existing bacteria like Rhodobacter can do all that and more.

The ability of ancestral mitochondria to make hydrogen, rather than use oxygen, was the basis of the primordial pact that gave rise to the eukaryotes, Martin and Müller argued. The bacteria produced hydrogen as waste, and the host cell used it to convert carbon dioxide into methane, gleaning a little energy from the process – just as many archaea, called methanogens, still do. The symbiosis began in an environment with little or no oxygen and only later, after the relationship was well established, did the host cell start exploiting the ability of the ancestral mitochondria to use oxygen.

This idea, known as the "hydrogen hypothesis", was proposed by Martin and Müller in 1998, but it has never gained widespread acceptance. It was not just up against the gut feeling of most researchers that the rise of the eukaryotes was related in some way to oxygen; on the face of it, what little evidence there was did not support it either.

Most studies of the genes needed to make hydrogenosomes, for example, suggest they evolved repeatedly and independently from mitochondrial genes, with some extra ones being picked up by lateral gene transfer from other organisms along the way. "I think the transformation from aerobic mitochondria to hydrogenosomes has little or nothing to do with the origins of eukaryotes," says microbiologist Mitch Sogin at the Marine Biological Laboratory in Woods Hole, Massachusetts.

Not surprisingly, Martin disagrees. "Single gene studies are subject to so many artefacts that we can conclude almost nothing about deep evolutionary history from them," he says. "Line up the same genes from the other end and you derive a totally different tree."

What's more, if aerobic mitochondria have evolved into hydrogenosomes on many separate occasions by picking up genes from other organisms, then why do hydrogenosomes always have the same small subset of genes for making hydrogen? They could have picked up all kinds of genes from bacteria, which have an amazing repertoire of metabolic abilities, Martin says, so why pick the same ones each time?

Remarkable abilities

Martin's explanation is simple: they share the same set because they inherited them from a single bacterium – the ancestor of mitochondria. For all its power, this argument is sterile without more evidence one way or another: you either believe it or you don't.

That evidence is starting to emerge. Take Naegleria gruberi, a curious shape-changing cell. In 2010 it was discovered that in the absence of oxygen, its mitochondria appear capable of generating energy by producing hydrogen, with the help of proteins also found in hydrogenosomes.

In the past few years, there have also been reports of the kind of large scale influx of genes that the hydrogen hypothesis predicts. In 2012, Shijulal Nelson-Sathi at the University of Düsseldorf, together with Martin and others, showed that the archaeon Haloarchaea had been transformed from strictly anaerobic to oxygen-using via the influx of a thousand bacterial genes. "This argues in favour of mass transfer of genes for entire pathways," says Martin. Likewise, 2015 research by Martin and others showed that the prokaryotic genes found in eukaryotes to enable photosynthesis and mitochondrial metabolism likely came about through episodic large scale transfer of genes, rather than gradual accumulation.

And now we have found animals that can live without oxygen lurking in brine lakes at the bottom of the Mediterranean. These species were discovered by marine biologist Roberto Danovaro of the Polytechnic University of Marche in Ancona, Italy, and his colleagues. They belong to an obscure group of microscopic animals, the Loricifera, found in ocean sediments around the world.

Little more than a millimetre long, the new species are so inactive that it took a while to prove they were indeed living, if not breathing. What's really striking about them, though, is not just their ability to live without oxygen but the way they manage it: unlike all other animals, including other loriciferans, they appear to have hydrogenosomes rather than mitochondria.

These recent discoveries are starting to transform people's perspectives. "The simplest explanation is that all the different types of mitochondria inherited their metabolic toolkits from a single versatile ancestor," says Mark van der Giezen at the University of Exeter, UK, who studies the evolution of anaerobic eukaryotes.

And if that is the case, then eukaryotes would have been able to live in anoxic environments right from the start. "Nobody seriously thinks that bacteria dwelling in such habitats only recently adapted to anaerobic niches," points out Martin. "But when it comes to eukaryotes, there is still a curious tendency to assume that they only invaded anaerobic niches of late. There's no logic in that."

Indeed, if the hydrogen hypothesis is right, the implications for complex life are striking. The existence of animals that don't need oxygen means that oxygen is not the be-all and end-all of complex life in the universe. The anoxic oceans a billion years ago might have been full of tiny creatures – as indeed many anoxic basins probably are today, if we look properly – and these animals got larger and more active when oxygen levels rose.

The deeper point relates to the origin of eukaryotes. There was no magisterial progression from simple to complex life as oxygen levels rose; no inevitability about it. Instead, there was a symbiotic union between a bacterium that could make hydrogen and an archaeal host cell that could exploit that hydrogen: a freak event that changed the world.

Living without breathing

Some fish, mussels and sediment-dwelling worms can live without oxygen for hours or even days. Instead of getting energy by "burning" food, the cells of these animals switch to ways of producing energy that do not require oxygen. Until recently, no animals had been discovered that go their entire lives without oxygen (see main story) – it was thought to be impossible.

Oxygen is not only used for getting energy from food, it is also needed to make compounds like collagen, the "glue" that holds animals together. No oxygen, no collagen; no collagen, no animals, the thinking went. That must be wrong, although we have yet to work out how the newly discovered animals make compounds like collagen without oxygen.

So could there be planets out there with large animals that do not need oxygen? While burning food produces 10 times as much energy as other means like fermentation, in theory an animal might get around that if it could somehow get 10 times as much fuel. The trouble is, fermentation leaves far less energy for predators in ecosystems. With aerobic respiration, there can be five or six links in a food chain before the amount of energy falls below 1 per cent of that available initially. Without oxygen, this happens with just two links.

And with far less scope for predation, animals might not evolve as far or as fast; the need to find prey or dodge predators is thought to have driven the development of features like eyes and mouths and muscles.

Nick Lane

The Origin of Life: Home and Dry

From New Scientist - 28 April 2016

THE ORIGIN OF LIFE

Home and dry

Water was probably the last thing the first life needed, says Colin Barras

"SOME warm little pond." Charles Darwin's speculative description of life's cradle, in a letter written to the botanist Joseph Hooker in 1871, still chimes today. Seed a watery environment with the right ingredients, Darwin mused, then cosset it with a little light, heat or electricity, and a purely chemical miracle of creation might occur.

Hard and fast evidence of how and where on Earth inanimate matter became animate is hard to come by. Other backdrops for life's first steps have gained in popularity since Darwin's time – around submarine hydrothermal vents, in ice or on Earth's radioactive first beaches, for example. If pressed, though, most of us would still plump for the primordial soup.

In the intervening years, we have devised more detailed recipes showing how the early Earth might have cooked up simple organic molecules, and how these might have reacted further to form the more complex building blocks of life: things like amino acids, DNA and RNA. Besides the right chemical ingredients, the process needs warmth, sunlight, perhaps a little lightning and, most importantly, H2O. Water is, after all, the essential solvent that underpins carbon-based life.

For Steven Benner, that is all a fairy tale. "We tend to think that water's properties are ideal for life, but the opposite is true," he says. "Water is corrosive." Benner is a chemist at the Foundation for Applied Molecular Evolution in Florida and for three decades he has been doing pioneering work in synthetic biology, which aims to recreate life's chemistry in the test tube. And he is no lone voice. As water's deleterious effects have become more apparent, many researchers are asking: is it time to dry out life's recipe?

Around 70 per cent of our planet's surface is ocean, and water makes up 60 per cent of our body weight. Few living things can survive for long without water: it is a perfect medium in which organic molecules can dissolve and react to sustain the core processes of life on Earth.

But this perfect solution is also a problem. Life's molecules don't just dissolve in water; the electron-rich oxygen of its molecules attacks them, and they begin to fall apart. "In your body right now, the DNA in your cells is losing an amino group many times a second because of the action of water," says Benner. Living things keep their molecules intact only through clever chemical strategies that perpetually repair the breakages.

Tricky when wet

The first life on Earth wouldn't have had time to develop those strategies. According to the widely accepted "RNA world" theory, RNA was the first self-replicating molecule, and a precursor to today's DNA-based life (see "Dawn of the living"). Like DNA, RNA is built up from nucleotides, complex organic molecules that are themselves formed from two simpler components, a nucleobase and a sugar called ribose. Decades of research have shown that making nucleotides in water is a very tricky business. Individual steps can be made to work, but they don't all gel together. "We are still at the stage of scraping out the product of step seven, and carefully spooning it into the flask to begin step eight," says Benner. Fail to spoon in just the right amounts of various molecules at the right time, and the end result is a gunky mess.

In 2004, Benner made a breakthrough. He showed that borates – minerals containing varying proportions of boron and oxygen – could act as scaffolds for the construction of ribose, making that part of the chemistry a much more hands-off, naturally plausible process. The problem of attaching the ribose to the nucleobases remained, however, until in 2012 Benner made a simple and bold suggestion: to make life, just remove water. By replacing it with an organic solvent richer in carbon and poorer in oxygen such as formamide (CH3NO), the right components would, in theory at least, stick together spontaneously to make RNA. This idea was bolstered by seminal work in 2015 showing that a simple set of chemical reactions can yield all the important building blocks of life, but only when the conditions are dry or nearly dry for some stages of the reaction.

Formamide would have been created when hydrogen cyanide in Earth's early atmosphere mixed with water. Its boiling point is higher than that of water, so in a hot environment the formamide would have become more concentrated as the water evaporated away.

Borates are scattered across Earth's surface today, where they result mainly from the erosion of igneous rocks. Looking at Earth now, Benner has found one environment that combines both sweltering conditions and the presence of borates. It aptly sums up how unexpected life's earliest requirements might have been. Its cradle, says Benner, might have looked a lot like California's Death Valley.

Benner's chemistry arguably provides the first one-pot recipe for life that can bubble away without human intervention. Armen Mulkidjanian, a chemist at the University of Osnabrück in Germany, is a fan. But he points to a problem with cooking it up in a primeval Death Valley. "The world's borate minerals are all found in relatively young rocks," he says. There is no evidence that surface concentrations of borates were sufficient for the chemistry to work until about 3 billion years ago, he says – around a billion years after life supposedly got started.

So where then? Mulkidjanian sees inspiration in the geothermal fields of Kamchatka in eastern Russia. These are spots where fluids have flowed through Earth's crust and come to the surface as vapours, bringing with them nutrients accumulated from rocks along the way. Borates are often found in these geothermal fumes, as are the chemical components of formamide. One further chemical convergence emboldens Mulkidjanian in thinking that a similar environment could have cradled life: the geothermal fields of Kamchatka are just about the only place on Earth where the balance of sodium and potassium ions matches that inside living cells.

Mulkidjanian's twist on Benner's tale has gained supporters. "What's nice is that geothermal fields provide a constant set of conditions for the origin of life, since the chemistry is coming from Earth's stable interior and not its exterior," says Ernesto Di Mauro at the Sapienza University of Rome, Italy. "If you frame Benner's proposal in these geothermal fields, you have a scenario that doesn't have many weak points."

But not so fast. These scenarios require Earth to have supplied dry environments like a Death Valley or a Kamchatkan geothermal field 4 billion years ago. Until recently, the consensus would have been that this was no problem: Earth was then exiting an interval dubbed the Hadean because of its hot and hellish conditions. But in the past decade, geologists have cooled on the idea of a hot young Earth. Their main evidence comes from tiny crystals, each less than a millimetre across, of a mineral called zircon. These are tough, easily outlasting the rocks they formed in, which have been obliterated by subsequent tectonic activity.

A close look indicates that the crystals were made in cool, soggy conditions, implying that Earth's early history was wet, with land accounting for perhaps just 5 or 10 per cent of its surface. Joseph Kirschvink, a planetary scientist at the California Institute of Technology in Pasadena, goes so far as to speculate there was no dry land at all. That leads him to a seemingly way-out conclusion: if the first life needed to be dry, it cannot possibly have started on

Earth.

Premature requiem

The search for life beyond our planet has also traditionally followed the mantra "follow the water" – although recent discoveries in and out of the solar system are causing that assumption to be revisited (see "Worlds without water", below). Kirschvink has been an enthusiastic supporter of the idea that Earth's life possibly began on Mars, ever since the infamous announcement in 1996 that fossilised "microbes" had been discovered in a 4.1-billion-year-old Martian meteorite called ALH 84001. The consensus now is that these are just rock features that look like cells – but we should not discount the Martian option just on that basis, according to Kirschvink. "The requiem for life on Mars was very premature," he says.

And if life needed a dry place to get started, Mars had the right conditions at the right time. Although it once had an ocean basin around its north pole, its southern highlands were almost definitely never submerged. "The RNA world would have done very well there," says Kirschvink. He thinks that later on, probably after the RNA world had given rise to the DNA-based cellular life we are familiar with today, an asteroid hit the Martian surface, throwing chunks of rock and ice containing these cells beyond the planet's atmosphere. Perhaps as little as nine months later, some of them made it to Earth.

In 2013, at the Goldschmidt geochemistry conference in Florence, Italy, Benner agreed that there is logic to Kirschvink's arguments. "The evidence seems to be building that we are actually all Martians; that life started on Mars and came to Earth on a rock," he said, generating a wave of media interest.

Just weeks before the conference, James Stephenson, now at the NASA Ames Research Center, California, and his colleagues had provided further succour for the theory, with confirmation that Mars is rich in a key ingredient for Benner's pathway. They published an analysis of a 1.3 billion-year-old Martian meteorite called MIL 090030 that showed it was riddled with boron. "I was honestly surprised that people hadn't really looked at boron in Mars samples before," says Stephenson. He hopes to collaborate with Benner soon to develop the idea further.

Mulkidjanian agrees that conditions on early Mars may have been suitable for the origin of life, and wryly points to evidence that the planet may even have had geothermal fields similar to those in Kamchatka, his favoured sort of cradle for life.

But he questions whether dry life arriving on a wet Earth on a Martian meteorite could have assimilated well. Genomic studies show that life on our planet traces back to a collection of cells that survived by sharing the products of their genes, creating a single-celled organism referred to as the last universal common ancestor (see "Meet your maker"). "If you dropped a primitive Martian cell into Earth's oceans, it is highly unlikely that it would have proliferated alone," he says. Rather, it would take a whole microbial ecosystem arriving, intact, from Mars.

Back to Darwin

This hints at a wider problem. No matter where and on what planet the delicate early forms of life originated, water's corrosive nature would have caused them to struggle when first introduced to a wet environment. All indications are that this happened very early: life has thrived in the oceans for billions of years. "There is a paradox," admits Benner. "You have to get out of water to solve the water problem, but then you've got to get back into the water." The only real solution, he says, is to gradually moisten a dry cradle and allow the variety of molecules to either cope or perish through natural selection.

Or we tweak our story still further. Nicholas Hud, a chemist at the Georgia Institute of Technology in Atlanta, points out that most researchers accept that DNA somehow evolved from RNA, so we should at least consider the possibility that RNA evolved from a different molecule that was stable in water. "When I look at RNA, I see a molecule that is perfect at what it does, but that's hard to make," he says – perhaps a telltale sign that natural selection helped shape RNA. "Which is more probable? Life began on Mars, was transported to Earth and picked up where it left off, or life began on Earth, but with a molecule different from RNA?"

Hud's thinking could remove the need for Kirschvink's Martian scenarios and Benner's chemistry, but would demand a rethink of the underlying assumption that life's chemical origin lies with RNA. It would seem fitting, though, that the ultimate solution to the water problem, even before life as we know it got started, could lie in the principles of natural selection. Stories about the origins of life begin and end with Darwin.

Worlds without water

Evidence that drinkable water once flowed on Mars, as found by NASA's Opportunity rover, is still lapped up as suggesting the planet could have harboured life. But with the realisation that water may have hindered early life on Earth (see main story), should we be looking elsewhere?

In fact, astrobiologists at NASA and elsewhere have long discarded the assumption that life needs aqueous chemistry. Earth and Mars aside, the solar system body thought most likely to harbour life is Titan, Saturn's largest moon. The Cassini probe, in orbit around Saturn since 2004, has shown Titan's dense atmosphere veils rough terrain but also smooth seas filled not with water, but the hydrocarbons methane and ethane. "Titan is an excellent place to explore for non-aqueous experiments in chemical self-assembly," says Jonathan Lunine, a planetary scientist at Cornell University in Ithaca, New York.

Lab experiments confirm that amino acids, the basis of proteins, could be generated on the surface of Titan, although temperatures are so frigid – as low as -180 °C – that life there would probably not be able to operate on Earth-like chemical principles. Covalent bonds of the sort that underpin our carbon chemistry would not form and break quickly enough, but weaker van der Waals bonds would be more stable and could play a more prominent part.

Whether life's origins were wet, dry or something else altogether, the different sorts of chemistry that might support life mean we should keep an open mind when considering the 2000-odd planets that missions such as NASA's Kepler space telescope have now found orbiting other stars, very few of which look like Earth. "We cannot limit ourselves to what we know in exploring the unknown," says Lunine. "We cannot simply search for the keys to life's origins underneath the narrow beam of the aqueous street lamp."

Colin Barras

Origin of LIfe: Inevitable, Fluke or Both?

THE ORIGIN OF LIFE

Life: Inevitable, fluke or both?

In theory, life ought to arise wherever conditions are right. But that doesn't mean the universe is teeming with creatures like us, says Nick Lane

FOR four years, the Kepler space telescope scoured the sky for Earth-like planets around other stars. When its mission ended in August 2013, it had found so many that NASA came to a startling conclusion: our galaxy is teeming with planets capable of hosting life. There are perhaps 40 billion of them, 11 billion of which are small rocky worlds orbiting sunlike stars at a distance where liquid water may exist.

These discoveries are bringing an old paradox back into focus. As physicist Enrico Fermi asked in 1950, if there are many suitable homes for life out there and alien life forms are common, where are they all? More than half a century of searching for extraterrestrial intelligence has so far come up empty-handed.

Of course, the universe is a very big place. Even Frank Drake's famously optimistic "equation" for life's probability suggests that we will be lucky to stumble across intelligent aliens: they may be out there, but we'll never know it. That answer satisfies no one, however.

There are deeper explanations. Perhaps alien civilisations appear and disappear in a galactic blink of an eye, destroying themselves long before they become capable of colonising new planets. Or maybe life very rarely gets started even when conditions are perfect.

If we cannot answer these kinds of questions by looking out, might it be possible to get some clues by looking in? Life arose only once on Earth, and if a sample of one were all we had to go on, no grand conclusions could be drawn. But there is more than that. Looking at a vital ingredient for life – energy – suggests that simple life is common throughout the universe, but it does not inevitably evolve into more complex forms such as animals. I might be wrong, but if I'm right, the immense delay between life first appearing on Earth and the emergence of complex life points to another, very different explanation for why we have yet to discover aliens.

Living things consume an extraordinary amount of energy, just to go on living. The food we eat gets turned into the fuel that powers all living cells, called ATP. This fuel is continually recycled: over the course of a day, humans each churn through 70 to 100 kilograms of the stuff. This huge quantity of fuel is made by enzymes, biological catalysts fine-tuned over aeons to extract every last joule of usable energy from reactions.

The enzymes that powered the first life cannot have been as efficient, and the first cells must have needed a lot more energy to grow and divide – probably thousands or millions of times as much energy as modern cells. The same must be true throughout the universe.

This phenomenal energy requirement is often left out of considerations of life's origin. What could the primordial energy source have been here on Earth? Old ideas of lightning or ultraviolet radiation just don't pass muster. Aside from the fact that no living cells obtain their energy this way, there is nothing to focus the energy in one place. The first life could not go looking for energy, so it must have arisen where energy was plentiful.

Today, most life ultimately gets its energy from the sun via photosynthesis by plants. But photosynthesis is an enormously complex process and probably didn't power the first life. So what did?

Reconstructing the history of life by comparing the genomes of simple cells is fraught with problems. Nevertheless, such studies all point in the same direction. The earliest cells seem to have gained their energy and carbon from the gases hydrogen and carbon dioxide. The reaction of H2 with CO2 produces organic molecules directly, and releases energy. That is important, because it is not enough to form simple molecules: it takes buckets of energy to join them up into the long chains that are the building blocks of life.

A second clue to how the first life got its energy comes from the energy-harvesting mechanism found in all known life forms. This mechanism was so unexpected that there were two decades of heated altercations after it was proposed by British biochemist Peter Mitchell in 1961.

Universal force field

Mitchell suggested that cells are powered not by chemical reactions, but by a kind of electricity, specifically by a difference in the concentration of protons (the charged nuclei of hydrogen atoms) across a membrane. Because protons have a positive charge, the concentration difference produces an electrical potential difference between the two sides of the membrane of about 150 millivolts. It might not sound like much, but because it operates over only 5 millionths of a millimetre, the field strength over that tiny distance is enormous, around 30 million volts per metre. That's equivalent to a bolt of lightning.

Mitchell called this electrical driving force the proton-motive force. It sounds like a term from Star Wars, and that's not inappropriate. Essentially, all cells are powered by a force field as universal to life on Earth as the genetic code. This tremendous electrical potential can be tapped directly, to drive the motion of flagella, for instance, or harnessed to make the energy-rich fuel ATP.

However, the way in which this force field is generated and tapped is extremely complex. The enzyme that makes ATP is a rotating motor powered by the inward flow of protons. Another protein that helps to generate the membrane potential, NADH dehydrogenase, is like a steam engine, with a moving piston for pumping out protons. These amazing nanoscopic machines must be the product of prolonged natural selection. They could not have powered life from the beginning, which leaves us with a paradox.

Life guzzles energy, and inefficient primordial cells must have required much more energy, not less. These vast amounts of energy are most likely to have derived from a proton gradient, because the universality of this mechanism means it evolved early on. But how did early life manage something that today requires very sophisticated machinery?

There is a simple way to get huge amounts of energy this way. What's more, the context makes me think that it really wasn't that difficult for life to arise in the first place.

The answer I favour was proposed 20 years ago by the geologist Michael Russell, now at NASA's Jet Propulsion Laboratory in Pasadena, California, who had been studying deep-sea hydrothermal vents. Say "deep-sea vent" and many people think of dramatic black smokers surrounded by giant tube worms. Russell had something much more modest in mind: alkaline hydrothermal vents. These are not volcanic at all, and don't smoke. They are formed as seawater percolates down into the electron-dense rocks found in the Earth's mantle, such as the iron-magnesium mineral olivine.

Olivine and water react to form serpentinite in a process that expands and cracks the rock, allowing in more water and perpetuating the reaction. Serpentinisation produces alkaline fluids rich in hydrogen gas, and the heat it releases drives these fluids back up to the ocean floor. When they come into contact with cooler ocean waters, the minerals precipitate out, forming towering vents up to 60 metres tall. Such vents, Russell realised, provide everything needed to incubate life. Or rather they did, 4 billion years ago.

Back then, there was very little, if any, oxygen, so the oceans were rich in dissolved iron. There was probably a lot more CO2 than there is today, which meant that the oceans were mildly acidic – that is, they had an excess of protons.

Just think what happens in a situation like this. Inside the porous vents, there are tiny, interconnected cell-like spaces enclosed by flimsy mineral walls. These walls contain the same catalysts – notably various iron, nickel and molybdenum sulphides – used by cells today (albeit embedded in proteins) to catalyse the conversion of CO2 into organic molecules.

Fluids rich in hydrogen percolate through this labyrinth of catalytic micropores. Normally, it is hard to get CO2 and H2 to react: efforts to capture CO2 to reduce global warming face exactly this problem. Catalysts alone may not be enough. But living cells don't capture carbon using catalysts alone – they use proton gradients to drive the reaction. And between a vent's alkaline fluids and acidic water there is a natural proton gradient.

Could this natural proton-motive force have driven the formation of organic molecules? I'm working on exactly that question. It is too early to say for sure, but the early signs are that the answer is yes.

What would that solve? A great deal. Once the barrier to the reaction between CO2 and H2 is down, the reaction can proceed apace. Remarkably, under conditions typical of alkaline hydrothermal vents, the combining of H2 and CO2 to produce the molecules found in living cells – amino acids, lipids, sugars and nucleobases – actually releases energy.

That means that far from being some mysterious exception to the second law of thermodynamics, from this point of view, life is in fact driven by it. It is an inevitable consequence of a planetary imbalance, in which electron-rich rocks are separated from electron-poor, acidic oceans by a thin crust, perforated by vent systems that focus this electrochemical driving force into cell-like systems. The planet can be seen as a giant battery; the cell is a tiny battery built on basically the same principles.

I'm the first to admit that there are many gaps to fill in, many steps between an electrochemical reactor that produces organic molecules and a living, breathing cell. But consider the bigger picture for a moment. The origin of life needs a very short shopping list: rock, water and CO2.

Water and olivine are among the most abundant substances in the universe. Many planetary atmospheres in the solar system are rich in CO2, suggesting that it is common too. Serpentinisation is a spontaneous reaction, and should happen on a large scale on any wet, rocky planet. From this perspective, the universe should be teeming with simple cells – life may indeed be inevitable whenever the conditions are right. It's hardly surprising that life on Earth seems to have begun almost as soon as it could.

Then what happens? It is generally assumed that once simple life has emerged, it gradually evolves into more complex forms, given the right conditions. But that's not what happened on Earth. After simple cells first appeared, there was an extraordinarily long delay – nearly half the lifetime of the planet – before complex ones evolved. What's more, simple cells gave rise to complex ones just once in 4 billion years of evolution: a shockingly rare anomaly, suggestive of a freak accident.

If simple cells had slowly evolved into more complex ones over billions of years, all kinds of intermediate cells would have existed and some still should. But there are none. Instead, there is a great gulf. On the one hand, there are the prokaryotes (bacteria and archaea), tiny in both their cell volume and genome size. They are streamlined by selection, pared down to a minimum: fighter jets among cells. On the other, there are the vast and unwieldy eukaryotic cells, more like aircraft carriers than fighter jets. A typical single-celled eukaryote is about 15,000 times larger than a bacterium, with a genome to match.

All the complex life on Earth – animals, plants, fungi and so on – are eukaryotes, and they all evolved from the same ancestor. So without the one-off event that produced the ancestor of eukaryotic cells, there would have been no plants and fish, no dinosaurs and apes. Simple cells just don't have the right cellular architecture to evolve into more complex forms.

Why not? I recently explored this issue with the pioneering cell biologist Bill Martin of the University of Düsseldorf, Germany. Drawing on data about the metabolic rates and genome sizes of various cells, we calculated how much energy would be available to simple cells as they grew bigger.

What we discovered is that there is an extraordinary energetic penalty for growing larger. If you were to expand a bacterium up to eukaryotic proportions, it would have tens of thousands of times less energy available per gene than an equivalent eukaryote. And cells need lots of energy per gene, because making a protein from a gene is an energy-intensive process. Most of a cell's energy goes into making proteins.

At first sight, the idea that bacteria have nothing to gain by growing larger would seem to be undermined by the fact that there are some giant bacteria bigger than many complex cells, notably Epulopiscium, which thrives in the gut of the surgeonfish. Yet Epulopiscium has up to 200,000 copies of its complete genome. Taking all these multiple genomes into consideration, the energy available for each copy of any gene is almost exactly the same as for normal bacteria, despite the vast total amount of DNA. They are perhaps best seen as consortia of cells that have fused together into one, rather than as giant cells.

So why do giant bacteria need so many copies of their genome? Recall that cells harvest energy from the force field across their membranes, and that this membrane potential equates to a bolt of lightning. Cells get it wrong at their peril. If they lose control of the membrane potential, they die. Nearly 20 years ago, biochemist John Allen, then at Queen Mary, University of London, suggested that genomes are essential for controlling the membrane potential, by controlling protein production. These genomes need to be near the membrane they control so they can respond swiftly to local changes in conditions. Allen and others have amassed a good deal of evidence that this is true for eukaryotes, and there are good reasons to think it applies to simple cells, too.

So the problem that simple cells face is this. To grow larger and more complex, they have to generate more energy. The only way they can do this is to expand the area of the membrane they use to harvest energy. To maintain control of the membrane potential as the area of the membrane expands, though, they have to make extra copies of their entire genome – which means they don't actually gain any energy per gene copy.

Put another way, the more genes that simple cells acquire, the less they can do with them. And a genome full of genes that can't be used is no advantage. This is a tremendous barrier to growing more complex, because making a fish or a tree requires thousands more genes than bacteria possess.

So how did eukaryotes get around this problem? By acquiring mitochondria.

About 2 billion years ago, one simple cell somehow ended up inside another. The identity of the host cell isn't clear, but we know it acquired a bacterium, which began to divide within it. These cells within cells competed for succession; those that replicated fastest, without losing their capacity to generate energy, were likely to be better represented in the next generation.

And so on, generation after generation, these "endosymbiotic" bacteria evolved into tiny power generators, containing both the membrane needed to make ATP and the genome needed to control membrane potential. Crucially, though, along the way they were stripped down to a bare minimum. Anything unnecessary has gone, in true bacterial style. Mitochondria originally had a genome of perhaps 3000 genes; nowadays they have just 40 or so genes left.

For the host cell, it was a different matter. As the mitochondrial genome shrank, the amount of energy available per host-gene copy increased and its genome could expand. Awash in ATP, served by squadrons of mitochondria, it was free to accumulate DNA and grow larger. You can think of mitochondria as a fleet of helicopters that "carry" the DNA in the nucleus of the cell. As mitochondrial genomes were stripped of their own unnecessary DNA, they became lighter and could each lift a heavier load, allowing the nuclear genome to grow ever larger.

These huge genomes provided the genetic raw material that led to the evolution of complex life. Mitochondria did not prescribe complexity, but they permitted it. It's hard to imagine any other way of getting around the energy problem – and we know it happened just once on Earth because all eukaryotes descend from a common ancestor.

Freak of nature

The emergence of complex life, then, seems to hinge on a single fluke event – the acquisition of one simple cell by another. Such associations may be common among complex cells, but they are extremely rare in simple ones. And the outcome was by no means certain: the two intimate partners went through a lot of difficult co-adaptation before their descendants could flourish.

This does not bode well for the prospects of finding intelligent aliens. It means there is no inevitable evolutionary trajectory from simple to complex life. Never-ending natural selection, operating on infinite populations of bacteria over billions of years, may never give rise to complexity. Bacteria simply do not have the right architecture. They are not energetically limited as they are – the problem only becomes visible when we look at what it would take for their volume and genome size to expand. Only then can we see that bacteria occupy a deep canyon in an energy landscape, from which they are unable to escape.

So what chance life? It would be surprising if simple life were not common throughout the universe. Simple cells are built from the most ubiquitous of materials – water, rock and CO2 – and they are thermodynamically close to inevitable. Their early appearance on Earth, far from being a statistical quirk, is exactly what we would expect.

The optimistic assumption of the Drake equation was that on planets where life emerged, 1 per cent gave rise to intelligent life. But if I'm right, complex life is not at all inevitable. It arose here just once in 4 billion years thanks to a rare, random event. There's every reason to think that a similar freak accident would be needed anywhere else in the universe too. Nothing else could break through the energetic barrier to complexity.

This line of reasoning suggests that while Earth-like planets may teem with life, very few ever give rise to complex cells. That means there are very few opportunities for plants and animals to evolve, let alone intelligent life. So even if we discover that simple cells evolved on Mars, too, it won't tell us much about how common animal life is elsewhere in the universe

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All this might help to explain why we've never found any sign of aliens. Of course, some of the other explanations that have been proposed, such as life on other planets usually being wiped out by catastrophic events such as gamma-ray bursts long before smart aliens get a chance to evolve, could well be true too. If so, there may be very few other intelligent beings in the galaxy.

Then, again, perhaps some just happen to live in our neighbourhood. If we do ever meet them, there's one thing I would bet on: they will have mitochondria too.

Nick Lane