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September 2002
Editor’s Note: A comprehensive, original paper on LUCA by A.M. Poole is also provided on this website as a supplement to this article.
Cells are so small that even a cluster of these cells from a mouse only measures 50 microns. Image from wikibook Cell Biology textbook, John Schmidt.
In the study of early life on Earth, one name towers above the rest: LUCA. LUCA is not the name of a famous scientist in the field; it is shorthand for Last Universal Common Ancestor, a single cell that lived perhaps 3 or 4 billion years ago, and from which all life has since evolved. Amazingly, every living thing we see around us (and many more that we can only see with the aid of a microscope) is related. As far as we can tell, life on Earth arose only once.
Answers in the genetic code
Life comes in all shapes and sizes, from us humans to bacteria. So how do we know that all life has evolved from a single cell? The answer is written in the language of the genetic code (Image A).
Image A: Table of standard (universal) genetic code. Source: NIH.gov.
- The genetic code is the language in which most genes are written into DNA.
- Such genes are recipes for making proteins.
- Proteins are what make the cell tick, doing everything from making DNA to digesting the food we eat and extracting the nutrients.
- Incredibly, the exact same code is used in humans and bacteria, so a gene from a human being can be put into a bacterium, and the bacterium will make the human protein — this is how insulin is made.
That the genetic code is universal to all life tells us that everything is related. All life regenerates itself by producing offspring, and over time small changes in the offspring result in small changes to the protein recipes. But because the recipes are written in the same language (the genetic code), it is possible to compare these recipes (and other genes) to build the equivalent of a family tree.
Family trees
Image B: Cluster of cells of Halobacterium sp. strain NRC-1. The Archaea are a group of single-celled microorganisms. Photo: NASA
Image C: Scanning electron micrograph of Escherichia coli bacilli bacteria. Image: NIH.
In this way, biologists have succeeded in making the mother of all family trees — the tree of life. The tree aims to establish the relationships between all living things, and has already revealed some surprises. Most striking is the discovery of the archaea (image B).1 These are simple organisms that, to look at them, are indistinguishable from bacteria (image C). 2 Before the prototype tree of life was built in 1977, it was thought that life had two major branches, the eukaryotes (e.g., plants, animals & fungi) and the prokaryotes (bacteria, and what are now known as archaea). The decision to split life into two branches was largely based on the visual difference between cells. Eukaryotes all possess a cell nucleus (image D) while prokaryotes (image E) don’t. But despite appearances, archaea and bacteria are as different from one another as either is from eukaryotes. So, the tree of life is now known to consist of:
- Archaea
- Bacteria
- Eukaryota
It is astounding that as recently as 25 years ago we were blissfully unaware that we and bacteria shared the planet with a third form of life!
Reconstructing LUCA
Image F: A phylogenetic tree of life. The very center represents LUCA. Pink represents eukaryota; purple-blue, bacteria; green, archaea. Source: Wikimedia Commons.
The tree of life is without doubt one of the great achievements in biology (image F). But for some researchers it is merely a means to an end. These researchers are trying to reconstruct LUCA, the cell from which all life has evolved.3 The question they are asking is, “which features of the archaea, bacteria and eukaryotes can be traced back to their common ancestor, LUCA?” This should be a very simple task — simply compare all three groups and choose the features that are common to all. By rights, LUCA’s reconstruction should be a done deal what with 70 or so complete genomes across the whole tree having been deciphered. (A genome houses all the genes in an organism, and a ‘catalogue’ of these genes is obtained by sequencing the organism’s DNA.) Unfortunately, it’s not that simple, for two reasons:
- genes get lost
- genes get swapped
How can we tell if a gene is ancient?
The implication of genes being lost is that when we compare genomes to see which genes are common across all life (that is, which are ‘universal’), we underestimate how many genes were originally in LUCA. Some of the genes that are not universal can be added to LUCA because clues to their origin can be found by looking at what they do. While we can make an educated guess as to whether a non-universal gene was in LUCA, most genes that are not universal are probably ‘new inventions’, specific to one of the three major branches of the tree. In fact, many may only be specific to one small group of, say, the archaea.
Another way to check if a gene is ancient is to look at whether it is a recipe for protein or RNA. This is an important clue because some RNAs date back to an even earlier period than the time when LUCA lived. The logic goes thus: if an RNA is older than LUCA, then LUCA had it too, even if that RNA is no longer universal.4,5
While dealing with gene loss is tricky, it is not an insurmountable hurdle — it just means reconstructing LUCA will be peppered with a lot of educated guesswork, and probably a few gaps. But gene swapping is another matter altogether — it threatens to fell the tree of life, and consign LUCA to the dustbin.6,7,8
Horizontal gene transfer
Gene swapping (or horizontal gene transfer as it’s often called by biologists) has been known about for decades. What biologists are only now beginning to look at is the extent to which genes are transferred between organisms. Comparing two bacteria from the same species reveals major differences.9 For example, Escherichia coli is a common gut bacterium that is part of our natural gut flora. But the O157:H7 strain causes severe gastrointestinal ailments. The genomes of both a harmless variant (K-12) and the O157:H7 strains have been deciphered and compared, and the result is striking.
- 1387 of the 5416 (26%) genes in O157:H7 are not in K-12.
- 528 of K-12’s 4405 (12%) genes are not in O157:H7.
Many of the O157:H7 genes are arguably foreign genes that have been borrowed from elsewhere. If we compare two people, or even a person with a chimpanzee, there’s nowhere near this kind of variation — humans all share the same genes, and humans and chimps may well have only a handful of genes that are different between our two species.
On a broader level, a now famous comparison of Escherichia coli K-12 to Salmonella enterica (another species of bacterium often responsible for food poisoning) concluded that:
- At minimum, 17% of the K-12 genome has been borrowed since these two bacteria split from a common ancestor around 100 million years ago.10
- LUCA would have roamed the Earth 3-4 billion years ago, so if all genes are so easily swapped, any evidence for LUCA would have effectively been scrambled because genomes are so severely shuffled.6
So where does this leave LUCA? A pessimist would say that LUCA is out of reach. However, it is far from obvious that all genes are equally swappable. Some, like genes for antibiotic resistance, are the gene equivalent of gypsies:
- when there is antibiotic present, they provide a bacterium with resistance11
- once the antibiotic disappears, they too are often lost
Other genes produce proteins that lock together with other proteins into large protein complexes, much like a 3D jigsaw. The ability for one jigsaw piece to be swapped with the equivalent jigsaw piece from another organism will depend on how similar the jigsaws are. Escherichia coli K-12 and O157:H7 could probably exchange such genes with relative ease, but a bacterium and an archaeon probably wouldn’t have a hope of doing so, even though such jigsaws perform the same biological role.12 Is gene swapping as common across other branches of the tree? We animals don’t tend to swap protein recipes like bacteria do, but we have done this in the past. There is now overwhelming evidence that we are part bacterium.13,14
- Our bacterial ancestry comes in the form of mitochondria (image G, tiny power plants housed in our cells.
- The DNA of your mitochondria is miniscule, with only a handful of genes. But mitochondria were once full-blown bacteria that took up residence in and struck up a partnership with one of our distant single-celled ancestors.
- Since then, much of the DNA from the original bacterium has been thrown away, but a lot of it has ended up in the DNA of our nucleus (image D).
The good news for LUCA biologists is that we seem to be pretty successful at identifying which bits of our nuclear DNA came from the mitochondrion, and which bits were already there. So to some extent, it might be possible to disentangle parts of the tree of life. But is it enough to save LUCA?
One or many LUCAs?
Carl Woese, one of the key players in the bid to reconstruct the tree of life, has added another twist to the LUCA puzzle. He has got researchers fired up by suggesting that:
- LUCA was also into gene swapping, and on a much larger scale than what we observe in modern bacteria
- gene swapping was once more important than inheritance from parent to offspring, and that early archaea, bacteria and eukaryotes each emerged independently from a ‘sea’ of gene transfer8
It’s not clear how his claims could be tested, but they are certainly food for thought — if he’s right there never was a single LUCA, but more of a community of genes loosely associated with cells.
The jury is still out as to how to reconstruct LUCA, and whether horizontal gene transfer will turn this task into a futile one. However, if not all genes are equal in the game of horizontal gene transfer, biologists stand an outside chance. Either way, there are plenty of exciting challenges, and many unknowns for those trying to build the tree of life and reconstruct our origins. For instance, just this year a member of a new group of microscopic archaea has been identified from a deep-sea trench.15 To give you some sense of perspective as to the significance of this discovery, it is roughly equivalent to discovering the first plant! Whether there was one or many LUCAs, these are definitely exciting times.
Editor’s Note: A comprehensive, original paper on LUCA by A.M. Poole is also provided on this website as a supplement to this article.
© 2002, American Institute of Biological Sciences. Educators have permission to reprint articles for classroom use; other users, please contact editor@actionbioscience.org for reprint permission. See reprint policy.
