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The Haida Indians of British Columbia believed
that after Raven (a mischievous, mythological creature) created this
earth ex nihilo (out of nothing), he coaxed the first humans
from a clam shell and made them the gift of fire.
The Judaeo-Christian tradition, on the other hand, endorses a sequential
creation of the non-living and living elements of the cosmos—plants
and animals first, then humans.
Creation narratives like these play a vital moral and inspirational
role in all our cultures. They ease the burden of individual mortality
and stake our species’ claim to at least one tiny corner of an
immense, indifferent universe. Although at different ends of the spectrum,
each narrative is an essential component of a revealed spiritual belief
system. There is a parallel narrative about the history of life in
the universe that is, at least in principle, discoverable through
scientific inquiry. But can this narrative truly provide spiritual
solace or guidance for those seeking it? Where do these individuals
turn for answers to the ancient questions about the origins of our
species?
Narrative, spirituality, and culture aside, perhaps these answers
lie in the tiniest organisms that were a major feature on the landscape
billions of years before man and woman ever appeared on the scene.
Looking for answers in the tiniest of places
Large organisms with recognizable hard parts have left a fossil record
for modern man to use as a resource and guide in the quest for answers.
Because of this record, we can formulate, test, and sometimes even
prove detailed evolutionary theories. For instance, using this approach
we can learn about the origins of mammals and birds from reptiles
between 150 million and 300 million years ago, or about the more recent
separation of humans, chimps, and other primates. In science, however,
it’s not always enough to travel back a mere 300 million years.
Sometimes a longer trip is necessary. In fact, my colleagues and I
are interested in events that happened much longer ago—about
two billion to four billion years—and that involved the tiniest
microscopic cells with few if any distinguishable morphological features.
In particular, to assist us in our efforts to piece together history,
we are interested in the origins of the very first cells, and the
evolution of complexity at the cellular level.
So how can we hope to reconstruct this history? My field, usually
called “molecular evolution,” is based on the premise that
a comparative analysis of sequences of molecules, in particular of
DNA, can replace the study of fossils. The underlying logic is simple.
As two species diverge in evolution from a common ancestor, their
genes will accumulate mutations. Some of these mutations will affect
the function of the protein or RNA that the gene encodes, and some
will be simply neutral. The longer the divergence, the more the accumulated
mutations. And the more the accumulated mutations, the greater the
difference between the genes. It is this difference between genes
(more precisely, gene sequences) that can be used as a measure of
evolutionary divergence. Typically, the pattern of differences is
represented as a phylogenetic tree, or genealogy—the Tree of
Life. As a result, we can reconstruct past events that gave rise to
the current panoply of similar and dissimilar creatures by isolating
and sequencing specific genes from their DNA.
Reconstructing the Tree of Life
Ever since our field was invented in the mid-1960s, reconstructing
phylogenetic trees from gene sequences in this way has been the major
preoccupation of molecular evolutionists. Since the beginning of the
1970s, most of us interested in recovering life’s most ancient
history have used sequences of a single kind of gene, called SSU rRNA.
The gene is known to be present in all organisms and is thought to
exhibit a regular, clock-like rate of accumulation of neutral mutations.
In fact, the publicly operated databases now contain almost 10,000
versions of this gene’s sequence, representing organisms across
the entire spectrum from E. coli to elephants.
What does the analysis of all this data show us? It shows us an enormous
twiggy tree, with three main branches. By studying this “Tree
of Life,” it becomes clear that all living things are located
on one of its three branches; they are either eukaryotes (you-carry-oats),
or one of two kinds of prokaryotes (pro-carry-oats)—bacteria
or archaea.
Eukaryotic cells are the kind with which we are most familiar. That’s
because almost all life forms that are big enough to be seen are eukaryotes.
The distinguishing characteristic is the nucleus, a membrane-bounded
compartment that surrounds the DNA. The DNA is the genetic material
or blueprint of the cell. In prokaryotes, however, the DNA is in free
contact with the rest of the cell contents. Undoubtedly, the first
eukaryotes (single, amoeba-like cells) arose somehow from the simpler
prokaryotes. Geochemical evidence suggests that this happened between
two billion and three billion years ago.
Of the prokaryotes, we are already well acquainted with bacteria.
Many of our worst diseases (plague, tuberculosis, necrotizing fasciitis)
are caused by bacteria. But many essential environmental services
(decomposition, recycling of carbon, nitrogen, and oxygen) also depend
on them. Archaea,
however, are the unexpected group and have shown themselves to have
unexpected biological idiosyncrasies. Some can grow at temperatures
as high as 115 degrees Celsius (under the sea); some are killed by
the smallest traces of oxygen; while others thrive only in saturated
brines.
The last type of archaea, the halophiles, have long been a Canadian
specialty. Al Matheson and Mak Yaguchi at the National Research Council,
and Donn Kushner of the University of Ottawa, pioneered research on
halophile ecology and physiology even before their evolutionary position
was revealed. My lab at Dalhousie University and that of Pat Dennis
at the University of British Columbia, were the first to apply modern
genetic tools to understanding their biochemistry.
Reconstructing the phylogenetic tree with SSU rRNA data has shown
us how complex eukaryotic cells could have arisen from simpler prokaryotic
antecedents. The current view is that eukaryotes are evolutionary
chimeras (named after the mythological monster with a lion's head,
goat's body, and serpent's tail). That means that the thousands of
genes that make up the eukaryotic genome ultimately derive from different
prokaryotic sources. Those genes responsible for key hereditary processes
and the expression of hereditary information (the “hardware”
of the cell) are derived from the archaea. Those genes responsible
for at least two key energy-generating processes—respiration
and photosynthesis (more akin to “software”)—are of
bacterial origin. Read
more about respiratory and photosynthetic genes.
For molecular evolutionists, the biggest surprise in recent years
has been the discovery that bacteria and archaea are themselves chimeric
(derived from different prokaryotic sources). This knowledge came
after the completion of more than three dozen bacterial and archaeal
genome sequences, each with its own complement of 500 to 5,000 genes.
By no means do all these genes produce the same phylogenetic tree
as SSU rRNA.
The driving force behind evolution
It is clear that the borrowing of genes across lineages (from one
kind of bacterium to another, from archaea to bacteria, or from either
to eukaryotes) has played a major role in the evolutionary process.
In some groups, it seems that it is gene borrowing not mutation that
has been the major source of functional novelty. As a result, it has
been the real driving force behind evolution. Some examples of consequences
of immediate relevance to us? The rise of antibiotic resistance in
known pathogenic bacteria (due almost entirely to transfer), and the
appearance of new pathogens (such as E. coli O157:H7)—often
the result of the transfer of clusters of virulence-promoting genes
called “pathogenicity islands.”
A new century with new ideas
The renowned British naturalist and evolutionist Charles Darwin (1809
to 1892) believed that a single phylogenetic tree would be the best
representation of life’s history. It would also be the best way
to account for the patterns of similarity and difference that we see
among contemporary organisms.
Today, at the beginning of the 21st Century, is there room for a different
viewpoint? Is our model of the Tree of Life still as relevant and
fruitful as we once believed? Perhaps not. If different genes have
followed different evolutionary paths, then there can be no such single
phylogenetic tree that can be reconstructed from gene sequences. For
bacteria and archaea, in order to visualize the pattern of history,
a web or net may be more appropriate than a tree. In a sense, bacteria
and archaea evolve as if they were a single global species, albeit
one within which rates of genetic exchange are highly variable and
generally slow. Sorin Sonea, a microbiologist at the University of
Montreal, actually said this about 30 years ago. However, at that
time, the implications of such a view seemed far too radical and the
support in evidence far too scant.
What does the future hold?
My own lab at Dalhousie University is now running full tilt to elaborate
the web or net model. We are testing its general validity and exploring
its implications through the acquisition and analysis of genomic (whole
genome) data. The general parameters that affect gene transfer—the
relatedness and physical proximity of the partners in exchange; the
genetic mechanisms involved; the classes of genes that can or cannot
be exchanged; selective pressures that drive the integration of new
genes; the consequences for the functions of resident genes—all
need to be worked out.
What do we hope to achieve? At the practical level, we would hope
to understand the spread of antibiotic resistance and pathogenicity
in an experimental/theoretical framework that would also encompass
the micro-organisms that do good things for us (in both polluted and
natural environments). At the philosophical level, we want to ask
how gene transfer threatens the very concept of species. At all levels,
we want to get a good feeling for the prevalence and power of gene
transfer. At the moment, too much of the data is still anecdotal or
ambiguous.
Research like this is so basic some might consider it arcane. We prefer
to see it as foundational. I consider myself blessed to have been
able to spend most of my career building this foundation. In this
effort, I have had as colleagues some of the world’s brightest
and most deeply motivated biologists, chemists, geneticists, and mathematicians—no
small number of them Canadians, and gratifyingly, many of them my
own students and postdoctoral fellows.
All that we understand and do in clinical and environmental biology
depends on a structure of prior knowledge, which we impart to our
students and apply in a variety of practical contexts. This structure
is not static. Although science does build incrementally, so that
much of what we learn today is a further detailed elaboration of established
generalities, sometimes those generalities are themselves overthrown.
This is where I think and hope we are in our understanding of the
first few billion years of the history of life, and of the genetic
structure of the microbial world—then and still.
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