by Nick Lane
C H A P T E R E I G H T
Looking for LUCA
Last Ancestor in an Age Before Oxygen
UCA, the last universal common ancestor, was baptized in the luminous light of Provence, in the south of France, in 1996. She was Lnamed at a rare meeting, a gathering of the tribes. Attending were chemists who study the primal stirrings of life, molecular biologists who trace the origins and evolution of genetic replication, thermophilists who study the bacteria living in hydrothermal vents at searing temperatures, microbiologists who decipher the metabolic traits of primordial life, and geneticists who compare and contrast the complete genomes of living organisms to unravel their evolutionary relationships. The name LUCA was a happy compromise between LUA, the Last Universal Ancestor, and LCA, the Last Common Ancestor, and is less clumsy and ugly than the scientific terms ‘cenancestor’ or ‘progenote’. LUCA conjures up images of Lucy, our own African forebear, and seems to encapsulate the trajectory of life on Earth. She (she has to be she) was a sympathetic entity who seeded life on our planet. She was not the first living thing, but rather the last ancestor common to all life known today, whether alive or extinct.
Together with the bacteria, algae, fungi, fish, mammals, dinosaurs, grass and trees, we all owe our lives to LUCA.
Where or when LUCA might have lived is controversial, but most researchers in the field now agree on a date of about 3.5 to 4 billion years ago. She was a single-celled form of life — though some think she might
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not even have been as sophisticated as a cell in the way we know it today
— and she probably lived in the ocean. Whether she lived a solitary life in an empty world, or mixed her genes with closely related cells, or fought a bitter evolutionary battle with quite different primordial forms of life, we do not know. If she did not live alone, then all her contemporaries have vanished without trace: LUCA seeded our planet as completely as biblical Eve seeded all humanity.
This means that LUCA’s properties are the basis of all subsequent evolution on Earth. We may reasonably infer that any features that are shared by all living things were once features of LUCA herself, and were passed on with varying degrees of modification to all her descendants.
Some attributes of present-day life, such as the ability to photosynthesize, are present only in some lines of descent, such as the purple bacteria, cyanobacteria and algae (which gave rise to plants), and so presumably evolved only in these lineages after the age of LUCA (unless they were independently lost by most of her descendants, which seems improbable but cannot be ruled out). The identity of LUCA may thus be pieced together, at least in theory, by comparing all the organisms that ever lived. The features that all organisms share were presumably inherited from LUCA herself.
Although comparing the properties of all living organisms might seem an impossible task, scientists have succeeded in defining a few of LUCA’s attributes. At first sight, these attributes may seem even more improbable, but they have an internal logic of their own. Most importantly, they agree with the evidence discussed in the last chapter. LUCA probably could use oxygen to generate energy before there was free oxygen in the air. She could defend herself against oxidative stress generated by ultraviolet radiation. Her defences came before, and enabled, the evolution of oxygenic photosynthesis. Oxygen radicals were therefore the ultimate driving force behind all sophisticated life on Earth. In this chapter, we will look at what we can learn from this emerging portrait of LUCA.
The poet and polymath Goethe once said that nothing in Italy makes sense until one has been to Sicily. For biologists, nothing makes sense without the theory of evolution, which offers an intelligible framework for interpreting the overwhelming variety of biological detail. The veracity of the theory of evolution by natural selection has been confirmed not so much by a single awe-inspiring experiment as by the every-day observations of a million biologists worldwide. These innumerable
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observations and discoveries have invariably upheld the fundamental unity of life.
The kinship of all living things is less than obvious if we look idly around us — what do we have in common with a mulberry bush? Yet when we begin to probe beneath the surface, the similarities become more and more clear. We share an extraordinary 98.8 per cent of our total DNA sequence with chimpanzees, for example. But then, we are both bipeds with arms and legs, heads, eyes, noses, ears, brains, hearts, kidneys, a circulatory system — we even have the same number of fingers. Size apart, most people could not distinguish the kidneys of a human being from those of a chimpanzee. Our behaviour and mating rituals can be compared with some profit. Few people would maintain that such similarity is coincidental. But, we also have a remarkable number of things in common with fishes, or even with the earliest indisputable ancestor of modern animals, a lowly worm. A worm, after all, has bilateral symmetry (it is the same on both sides), a rudimentary heart, a circulatory system, a nervous system, eyes, a mouth and an anus. Unlike plants, it moves around and burrows holes in the sand.
As late as the 1950s, textbooks continued to cite the obvious differences between plants and animals, retaining Linnaeus’s original sub-division of life into the two great kingdoms of Plantae and Animalia. But the dichotomy was breaking down, and was soon to be replaced by a new classification comprising five kingdoms, proposed by R. H. Whittaker in 1959: animals, plants, fungi, protists (a mixed bag including protozoa and algae) and bacteria. The new system had simplicity and convenience on its side, and for these reasons is still in common use today. Despite its honest virtues, though, it suffers a fundamental flaw. The problem is that the distinctions between the five kingdoms were based on morphology or behaviour rather than genetic ancestry. Holding a distorting mirror up to the problem, it is a little like classing a fly-eating plant and a woodpecker together on the grounds that both are multicellular and both devour insects. In reality, plants, animals, fungi and protists are much closer cousins than their visible appearance or their behaviour would have us believe. This kinship is at the cellular level, and only becomes evident under the microscope. When we consider the structure of their cells, these four kingdoms have far more in common with each other than any of them do with the fifth kingdom, the bacteria. The similarities are so fundamental that these four kingdoms are classed together as members of a single overarching taxonomic group, or domain, called the eukaryotes,
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from the Greek meaning ‘with true nuclei’. All eukaryotes have a nucleus, the largest thing in the cell. It is a roughly spherical structure separated from the rest of the cell — the cytoplasm — by a double membrane. Most eukaryotic cells range from around a hundredth to a tenth of a millimetre (10–100 micrometres) in diameter, although there are exceptions, including our own nerve cells, which have fine projections that can be over a metre [several feet] long. The cytoplasm of a eukaryotic cell is crammed with assorted jumble — hundreds or even thousands of tiny specialized organs, called organelles, such as mitochondria (in virtually all eukaryotes) and chloroplasts (in algae and plants), mixed up with small sacs of membrane, stacks of folded membranes and a protein skeleton. This riot of compartmentalization gives eukaryotic cells the look of evolution by conglomeration, which is indeed what happened, as we saw in Chapter 3.
The nucleus contains the genetic heritage of eukaryotic cells — an oddly amorphous-looking material known as chromatin, made of DNA wrapped in proteins. When eukaryotic cells divide, the DNA is first replicated and then the chromatin condenses into tight coils, or chromosomes, which are eased apart on a protein framework to form two new nuclei. The detailed structure of eukaryotic genes came as one of the greatest surprises of molecular biology in the last quarter of the twentieth century. Far from being continuous compact coding sequences, neatly lined up like beads on a string, as we once imagined (and as bacterial genes had been shown to be), eukaryotic genes are discontinuous and compri
se just a few per cent of the cell’s total DNA. Most eukaryotes have
‘genes in pieces’, where the pieces of the gene coding for the protein product are interspersed with long tracts of apparently junk DNA, coding for nothing. Individual genes are also separated by large stretches of apparently junk DNA. Much of this extraordinary excess is thought to be
‘selfish’ DNA, which hitches a ride in the cell simply to get itself replicated, contributing nothing to the common good. Other stretches of junk DNA are the sunken wrecks of genes, holed by mutations below the water-line, such as our own derelict gene for producing vitamin C.1 The eukary-1 The gene for making vitamin C still works in plants and in most animals, as we shall see in Chapter 9. Its sequence is comparable to the remains of our broken gene. We, or at least our ancestors, must once have eaten enough vitamin C from plants to satisfy our needs, since the loss of our gene for producing vitamin C was not penalised by natural selection, as it most certainly would have been had the deficit proved counter-adaptive. In general, a good guide to the importance of a gene is the degree of suffering caused by its loss. The loss of some genes is incompatible with reproductive vigour, or even with life. Most very ancient genes that are still in working order are very important — their loss has been punished repeatedly by the personal extinction of the bearer or their lineage.
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otes, cells with ‘true nuclei’ hardly live up to their name. If we were to rename them today, any notion of ‘truth’ would surely be dismissed from their name. Eukaryotes are a tissue of lies, in the sense that they are not at all what they seem.
Bacteria are built on a totally different ground plan. Most important, they have no nucleus, and so are classified in a separate domain as prokaryotes, meaning simply ‘without nuclei’. They are much smaller than eukaryotes, usually only a few micrometres in diameter, and are encased in a rigid cell wall, giving them the appearance of tiny capsules. The bacterial cell wall is composed of peptidoglycans, long chains of amino acids and sugars. Many types of eukaryotic cells also have cell walls, but none are made of peptidoglycans.
Bacterial genes are naked, in that the DNA thread is not wrapped around with proteins. Bacteria have a fraction of the number of genes of most eukaryotes — a few thousand, instead of tens of thousands. They organize these genes into groups with similar function, known as operons, and carry very little junk DNA. Nor are they encumbered with stacks of internal membranes, protein skeletons or organelles such as mitochondria. This lack of clutter allows them to divide at huge speeds simply by binary fission, or splitting in half. They can also recombine their genes with those of other bacteria by what amounts to copulation — the direct injection of genes into a neighbouring bacterium in a process known technically as conjugation. This allows genetic innovations, such as resistance to antibiotics, to spread rapidly through an entire bacterial population. In comparison with the eukaryotes, which lumber like battle-ships, bacteria have the evolutionary speed and agility of fighter aircraft.
The gulf between prokaryotes and eukaryotes is genuinely deep, but the two groups are clearly related at a fundamental level — the biochemistry of their cells. This is the kind of detail that persuades biologists that all living things on Earth are indeed related. As the proverb says, there are many ways to skin a cat. The fact that all life systematically follows the same way, step by step, suggests that all life has been following the same set of instructions from the very beginning. The genes in all cells, for example, are made from DNA (deoxyribonucleic acid). DNA constitutes a four-letter ‘genetic code’, which stipulates the sequences of the amino-acid building-blocks in proteins. The code is, to all intents and purposes, identical in all living things. Not only this, but the detailed mechanism by which proteins are built, following the instructions encoded in DNA, is the same in all cases. The sequence of letters in DNA is read off, or
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transcribed, into a rather similar molecule called messenger RNA (ribonucleic acid). This carries the instructions for building a particular protein from the gene to the protein-assembly stations, tiny molecular machines called ribosomes where all the action takes place. Here, on the ribosomes, the coded message is translated into a protein. This is done in the same way in all cells, using a repertoire of ‘adaptor’ molecules, also made from RNA, but this time with amino acids in tow. These adaptors are called transfer RNA. The molecules of transfer RNA recognize sequences of letters in messenger RNA and match them with the appropriate amino acid. Essentially the same process takes place in all living organisms, making use of the same code, the same messenger RNA and transfer RNA, the same ribosomes and the same amino acids. For Mother Nature, it seems, there is only one way to skin a cat.
The conclusion from all this — that all life on Earth has a common ancestor — is backed up, most convincingly of all, by the surprising unity of life at its most basic level: the ‘handedness’ of individual molecules.
Many organic molecules, including amino acids and simple sugars, exist in two mirror-image versions, analogous to the left hand and right hand of a pair of gloves. Both hands are equally abundant in nature, and there is no reason why one should be used by living organisms instead of the other. Once a decision has been taken, though, it is hard to swap. A left-handed glove will never fit on the right hand. Similarly, an enzyme that catalyses the reactions of a left-handed molecule is useless when con-fronted with the right-handed version. Once that enzyme’s sequence of amino acids has been encoded in the DNA, it is too late to swap. To make two mirror-image enzymes that work with opposite-handed molecules is a waste of resources: life must make a random choice and then stick to it.
Given a random choice, we might expect that some species would have right-handed molecules, and others left-handed molecules (making full use of natural resources), but this is not the case. All life is right-handed in its molecular preference. The only sensible explanation for this extreme conservatism is that LUCA herself was right-handed — a historical accident — and that all her descendants have been obliged to follow suit.
When did LUCA give rise to her diverse offspring? Cells resembling modern prokaryotes date back 3.5 billion years, to the stromatolites in south-western Australia, as described in Chapter 3. The first signs of eukaryotic cells, the biomarkers of membrane sterols, date to about 2.7 billion years ago. The first unequivocal eukaryotic fossils are found
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in rocks dating to about 2.1 billion years ago. An explosion in the number and variety of eukaryotic cells took place around 1.8 billion years ago.
Eukaryotic cells share their fundamental biochemistry with prokaryotes, but are larger and more complex. It seems likely that only the innate complexity of the eukaryotic cell can support the added layers of organization required for the evolution of multicellular life. Certainly, all true multicellular organisms are eukaryotes. Taken together, these bare facts suggest that the prokaryotes were the first primitive cells (as suggested by their name), and that the more advanced eukaryotes evolved from them later, gradually accruing complexity.
Many features of the eukaryotes support this conclusion. During the mid-1880s, the German biologists Schmitz, Schimper and Meyer proposed that chloroplasts were derived from cyanobacteria. In 1910, the Russian biologist Konstantin Mereschovsky took this idea further, arguing that eukaryotic cells had evolved from a union of different types of bacteria. With only rudimentary microscopic techniques to back up his arguments, however, he failed to convince the biological establishment.
His ideas stagnated for nearly 70 years until the late 1970s, when Lynn Margulis, at the University of Massachusetts at Amherst, championed the cause and marshalled evidence that organelles were once free-living bacteria, at a time when new molecular methods could prove the case.
It is now accepted, as one of the basic tenets of biology, that chloroplasts and mitochondria (the energy ‘power-houses’ of eu
karyotic cells) were once free-living bacteria. Many details betray their former status.
Both, for example, retain a genetic apparatus, including their own DNA, messenger RNA, transfer RNA and ribosomes. These bear witness to their bacterial origins. Mitochondrial DNA, for example, like bacterial DNA, comes packaged as a single circular chromosome, and is naked (not wrapped in proteins). The sequence of letters in its genes is closely related to the equivalent genes in a class of purple bacteria called the alpha-proteobacteria.2 Mitochondrial ribosomes also resemble those of the proteobacteria in their size and detailed structure, as well as their sensitiv-2 Mitochondria are also purple, and are in fact one of the few coloured components of the cell. In a vivid aside in The Energy of Life, Guy Brown remarks that ‘were it not for the melanin in our skin, myoglobin in our muscles and haemoglobin in our blood, we would be the colour of mitochondria. And, if this were so, we would change colour when we exercised or ran out of breath, so that you could tell how energized someone was from his or her colour.’
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ity to antibiotics such as streptomycin. Again, like bacteria, mitochondria divide simply by splitting in half, usually at different times from each other and from the rest of the cell.
Despite these atavistic features, mitochondria have lost almost all their former independence. Two billion years of shared evolution have left the mitochondrial genome with little to call its own. Its closest bacterial relatives, the alpha-proteobacteria, have at least 1500 genes, whereas the mitochondria of most species have retained less than a hundred. As we saw in Chapter 3, evolution tends towards simplicity as readily as complexity. Any bacterial genes unnecessary for survival inside the eukaryotic cell would have been quickly lost, as genes in the nucleus could take over their role without competition or antagonism. Other mitochondrial genes have physically moved to the nucleus — 90 per cent of the genes that determine mitochondrial structure and function now reside in the cell nucleus. Why the remaining 10 per cent of genes stayed put in the mitochondria is something of an enigma, but their location probably confers some sort of advantage.