Ridley Matt, The Search for LUCA, "Natural History", Vol. 109, No. 9,
November 2000, pp.82-85.
 

FINDINGS

The Search for LUCA

Did the Last Universal Common Ancestor look like a bacterium-or like one
of your own cells?

By Matt Ridley

EUKARYOTE FAMILY PORTRAIT

What was the first organism with DNA like? Scientists have traditionally
assumed it was some kind of primitive bacterium.. But recent research
suggests that the long looked for "it" may have been more of a "them." And
according to a controversial new theory, the first organisms equipped with
DNA may have resembled one of our own cells more closely than they
resembled bacteria.

All living creatures-be they amoebas beech trees, beetles or bacteria-
share a common ancestor that lived about 4 billion years ago. We infer the
existence of this Last Universal Common Ancestor-or LUCA-from the many
features shared by all organisms, most notably the unique code that
translates the language of DNA into the language of proteins, the things
that actually do all the work inside cells. If there were other, rival
life-forms here on Earth, they died out long ago.

By comparing the similarities and differences in the genes of different
organisms, we can climb down the family tree and observe where it
branches. Take our own lineage. Five million years ago, the Homo sapiens
branch meets that of chimpanzees; a few million years before that, the
common ancestor of humans and chimps merges with gorillas; and so on, back
to the first mammal, the first reptile, the first vertebrate, the first
multicellular animal. Finally we get to the common ancestor of all
animals, plants, protists, and fungi. This undoubtedly tiny organism was
the last common ancestor of all present-day eukaryotes (organisms
possessing cells with a nucleus). At this juncture, scientists long
thought, there was only one convergence left: between eukaryotes and
prokaryotes (single celled organisms with no nucleus). For most of the
twentieth century, prokaryotes had generally been considered synonymous
with bacteria. But in 1977 Carl Woese, of the University of Illinois,
found a fundamental division within the prokaryotes: between bacteria and
what he called archaea, a diverse group of cells that look very like
bacteria but differ genetically and are often found in extremely hot
environments, such as hot springs, with temperatures above 203o F. Woese
totted up the genetic differences between the two kinds of prokaryotes and
concluded that the trifurcation of life into eukaryotes, bacteria, and
archaea-must have occurred more than 3 billion years ago. But which of the
three groups appeared first? Are we eukaryotes more closely related to
bacteria or to archaea? To find out, researchers in the mid-1980s turned
to the enzyme RNA polymerase and other factors involved in the synthesis
of proteins, some of the most ancient and universal pieces of machinery in
the cell. After comparing these proteins in species from the three groups
of organisms, the scientists concluded that plants, animals, and fungi are
more closely related to archaea than to bacteria. Comparisons of other
proteins, however, contradicted this conclusion: some suggested that
eukaryotes and bacteria were closer kin, while still others suggested that
archaea and bacteria were.

By the mid-1990s, the situation had become a mess. The only explanation
for these contradictory patterns, according to W Ford Doolittle, of
Dalhousie University in Nova Scotia, is to assume that at some point in
the early history of life, there was promiscuous sharing of genes among
species-or even mergers of whole organisms. Woese agrees. He now thinks
that "the Last Universal Common Ancestor was not a discrete entity but
rather a diverse community of cells that evolved as a biological unit."

There the matter might have rested but for a meeting convened in 1996 at
Les Treilles, near Paris, to discuss the confusing tree of life. Attending
that meeting was Patrick Forterre, a scientist from the Universite
Paris-Sud. Forterre had a heretical view. He challenged the generally
accepted idea that bacteria (or archaea) predated all other creatures on
Earth. He even doubted that they were primitive. The long-standing
"prokaryote dogma," he claimed, was based on the prejudice that the simple
must precede the complex. His own work on a bacterial enzyme called DNA
gyrase had convinced him that bacteria are actually quite advanced. Gyrase
is a powerful and sophisticated tool-and it's a tool eukaryotes do not
possess. The more Forterre considered the streamlined simplicity and
effectiveness of a bacterial cell, the more he was convinced that the
flunky machinery in eukaryotic cells represented an older, more primitive
technology.

Forterre and his colleague Herve Philippe have now gathered many examples
that support their case. Take RNA polymerase. This enzyme creates working
copies of DNA (called messengers) used in gene translation. The version we
eukaryotes use has up to thirteen components, each made by a separate
gene. In addition, it is assisted by twenty or so
"transcription factors," by a ten-part "spliceosome" (a machine whose job
it is to cut out the pieces of nonmessage text, called introns, that
interrupt eukaryotic genes), and by a six-part "polyadenylation device."
The RNA polymerase used by archaea also has a large number of components
(eight to twelve) and is assisted by only two or three other genes.

The truly striking contrast, however, appears in the version used by
bacteria, which has just three components and a single assistant. The
traditional view would be that the complications found in eukaryotic RNA
polymerase were added over the eons. But it could just as easily have
happened the other way round, with bacteria slimming down the RNA
polymerase machinery to its most efficient form. In plants, animals, and
fungi, the synthesizing, capping, splicing, polyadenylating, and
transporting of a DNA messenger takes about thirty minutes. In bacteria,
the process is completed in a matter of seconds.

Forterre argues that his scenario of moving from a complex eukaryote-like
common ancestor to a simpler but more efficient prokaryotic system is more
appealing than the classical hypothesis that views prokaryotes as the more
primitive organisms. Appealing, maybe but how strong a case can be made
for his idea?

There is no question that simplification does occur during evolution. Over
time, parasitic lineages lose sense organs and brains they do not need.
Microsporidia are a good example. These pathogens were once thought to be
a missing link between primitive prokaryotes and advanced eukaryotes
because they are so simple and because they lack mitochondria. We now know
that microsporidia are nothing so special- they're merely cousins of fungi
that have become drastically simplified by their parasitic life. Likewise,
many biologists are convinced that viruses, which borrow the biochemistry
of their hosts to reproduce themselves, are not derived from primitive
independent life-forms but are little packets of rogue genes that have
escaped from higher organisms. If viruses are reduced organisms, then why
couldn't bacteria be as well?

The eukaryotic cell is stuffed full of features that have no counterpart
in bacteria or archaea and that, Forterre argues, no self-respecting
life-form would invent unless it absolutely had to. We eukaryotes have
telomeres, for example: specially constructed caps of DNA on the ends of
chromosomes that prevent the tips from fraying. (Fraying is now thought to
be one of the chief symptoms of aging.) But telomeres are unnecessary in
bacteria, which have circular chromosomes and thus no ends to fray. And
then there are our spliceosomes: bacteria have no introns and thus no need for spliceosomes.

The most convincing part of Forterre's case is an argument developed by
three New Zealanders: Anthony Poole, Daniel Jeffares, and David Penny, all
at Massey University. They point out that a great many of the special
features of eukaryotes have working components made of molecules of RNA,
which is almost universally regarded as the primitive precursor of DNA.
Telomerase, the enzyme that repairs telomeres, has working RNA inside it.
So does the spliceosome. And RNA is meres, has working RNA inside it. So
does the spliceosome. And RNA is crucial to the synthesis of proteins. The
presence in eukaryotic cells of these working machines made from a more
ancient material suggests to Forterre and his like-minded colleagues that
they are relics of an earlier age.

Moreover, RNA has a property that DNA lacks almost entirely-it can act as
a catalyst to assist chemical reactions. Most current hypotheses about the
history of life before LUCA envisage an entire RNA world of
"riboorganisms," with RNA genes and RNA enzymes. Only later, according to
these hypotheses, did some fortunate descendant invent both the much
subtler catalytic machinery of protein and the much more chemically stable
information-storage device called DNA. At that point, RNA was demoted to
being the link between DNA and proteins.

If the scenario of an ancestral RNA world is correct, then why, Forterre
asks, do eukaryotes have much more complicated RNA machinery in their
cells than bacteria and archaea do? And if, as Poole and his colleagues
say, all these RNA devices are indeed molecular "living fossils" left over
from a different world, then it seems unlikely that eukaryotes would have
invented all this machinery to complicate their lives and used an old
technology to do so. That would be a bit like finding wooden parts working
in the innards of a computer.

Additional support for the idea that eukaryotes evolved before prokaryotes
can be seen in the structure of their chromosomes. Each chromosome is a
very long molecule of DNA. We humans hare twenty-three pairs of them -
forty-six separate DNA molecules. Other species of eukaryote have
different numbers of paired DNA molecules, but in all of us, the molecules
come in separate chromosomes. Compare this with the single, circular
chromosome of bacteria and archaea. Now imagine one system evolving from
the other. If the prokaryotic system came first, the eukaryotes would have
had to chop the ancestral chromosome into sections, add telomeres to their
ends, and drop the equipment that closes the circle.

If, however, the eukaryotic system arose earlier, the machinery for making
a single circular chromosome would already have been in place: a single
enzyme called reverse transcriptase. This enzyme makes a circular DNA copy
of an RNA transcript (after the introns have been edited out by the
spliceosome). Multiple copies of reverse transcriptase are present in all
genomes, having been left there by retroviruses containing genes for the
enzyme. The Forterre-Poole hypothesis envisages that some primitive
retrovirus left behind a reverse transcriptase gene in a proto-eukaryotic
organism, which used it by chance, one day, to make a circular chromosome.

And separate linear chromosomes may not be the only primitive feature of
our genome: the very habit of using pairs of chromosomes, one from each
parent, may also be a relic from the days when transcription errors were
more common and spare copies would thus have come in handy.

If Forterre and Poole are right about eukaryotes being the steam engines
of the living world, then how did we manage to remain so successful? The
answer may lie in several features of modern eukaryotic cells that
bacteria have not invented-in particular, the ability to engulf other
cells. This talent allows some protozoa (single-celled eukaryotes) to
pursue a largely predatory way of life. It is also the source of our
immune system's ability to consume or otherwise incorporate invading
bacteria and sometimes to benefit by their presence. Some bacteria
engulfed in this way went on to become mitochondria, symbionts living
inside the eukaryotic cell and providing it with energy. In addition, the eventual
evolution of multicellularity in eukaryotes brought the immense advantages
that accompany division of labor in a large body and helped offset the
biochemical disadvantages of poorly developed genetic machinery.

As with most attempts to reconstruct the history of life, Forterre's
argument for a eukaryotic LUCA would be greatly strengthened by fossil
evidence. The oldest known fossils are the 3.5-billion-year-old
stromatolites discovered in western Australia in 1980. These small,
pillow-shaped structures were almost certainly laid down by living
organisms, but it is difficult to determine for certain what kind of
creature built them. Modern stromatolites are usually--but not always-made
by bona fide prokaryotes, and the common assumption is that the ancient
ones were, too. But there is no hard evidence for this. And last year
Jochen Brocks and his colleagues at the Australian Geological Survey
Organisation made a remarkable discovery. They extracted hydrocarbon from
2.7-billion-year-old shales in the form of bitumen and subjected it to
spectrographic analysis to see what it was made of. They were surprised to
find a group of compounds called steranes-hydrocarbons made by eukaryotes
but not by prokaryotes. The result, they say, provides persuasive evidence
for the existence of eukaryotes 500 million to 1 billion years before the
fossil record currently indicates that the lineage arose. In other words,
the "age of prokaryotes," which all the textbooks say preceded the age of
eukaryotes, might never have existed.

Forterre's theory has by no means won the field. But he has done a great
service by pointing out what a naked emperor the prokaryotic dogma may
turn out to be.
 

Matt Ridley is the author of Genome: The Autobiography of a Species in 23
Chapters, an adaptation of which appeared in the March issue of Natural History.

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