Microcosm (18 page)

Nine

PALIMPSEST

BURIED MESSAGES

         
WHEN SCIENTISTS PUBLISHED THE FIRST
genome of
E. coli
in 1997, they titled it “The Complete Genome Sequence of
E. coli
K-12.” Strictly speaking, the title was a piece of false advertising. Nowhere in the paper can you find the raw sequence of 4,639,221 bases. The omission was simply a matter of space:
E. coli
K-12’s genome would fill about a thousand journal pages. Those who crave a direct confrontation with its genetic code must visit the Internet.

One of the sites that houses its code is the Encyclopedia of
Escherichia coli
K-12 Genes and Metabolism, EcoCyc for short. EcoCyc displays the K-12 genome as a horizontal line stretching across the screen, scored with a hash mark every 50,000 bases. If you click on the mark labeled “1,000,000,” you will zoom in on the 20,000 bases that straddle that point in the genome. Bars run above the line to show the location of individual genes. Click on the bar for the gene pyrD and you can read its sequence. If you seek something more meaningful, you can also read about pyrD’s function (creating some of the building blocks of RNA). On EcoCyc you can learn about the network of genes that controls when pyrD switches on and off.

If you browse EcoCyc for very long, you may fall under a peculiar spell. You may begin to imagine its genome as an instruction manual for an exquisite piece of nanotechnology crafted by some alien civilization. Its genome holds all the information required to assemble and run a sophisticated machine that can break down sugar like a miniature chemical factory, swim with proton-driven motors, and rewire its networks to withstand stomach acids and cold Minnesota winters.

Let that delusion pass.

If you look long enough at
E. coli’
s genome, you will come across hundreds of pseudogenes, instructions with catastrophic typographical errors. You will encounter the genes of viruses that respond to stress by making new viruses and killing their host. Other instructions are mysteriously clumsy, redundant, and roundabout. Still others are cases of outright plagiarism.

Where the metaphor of an instruction manual collapses, other metaphors can take its place. My favorite is an old battered book that sits today in a museum in Baltimore. It was created in Constantinople in the tenth century. A Byzantine scribe copied the original Greek text of two treatises by the ancient mathematician Archimedes onto pages of sheepskin. In 1229, a priest named Johannes Myronas dismantled the book. He washed the old Greek text from the pages with juice or milk, removed the wooden boards, and cut the binding strings on the spine. Myronas then used the sheepskin to write a Christian prayer book. This sort of recycled book is known as a palimpsest.

Despite its new incarnation, the Archimedes palimpsest carried traces of the original text. The prayer book was passed from church to church, scorched in a fire, splashed with candle wax, freshened up with new illuminations, and colonized by purple fungus. In 1907, a Danish scholar named Johan Heiburg discovered that the battered prayer book was in fact the only surviving copy of Archimedes’ treatises in their original Greek. But with only a magnifying glass to help him, Heilburg could make out very little of the ancient text. A century later conservationists are making more progress. They are illuminating Archimedes’ works with beams of X-rays that light up atoms of iron in the original ink, resurrecting a glowing text of Greek. The palimpsest reveals new depths to the genius of Archimedes, who turns out to have been contemplating calculus and infinity and other concepts that would not be rediscovered for centuries.

E. coli’
s genome is not so much a manual as a living palimpsest.
E. coli
K-12, O157:H7, and all the other strains evolved from a common ancestor that lived dozens of millions of years ago. And that common ancestor itself descended from still older microbes, stretching back over billions of years. The genetic history of
E. coli
is masked by mutations, duplications, deletions, and insertions. Yet traces of those older layers of text survive in
E. coli’
s genome, like vestiges of Archimedes.

Until recently, scientists had only crude tools for reading those hidden layers. They struggled like Heiberg with his magnifying glass. They are now getting a much better look at the palimpsest. Like Archimedes’ ancient treatise, they’re finding,
E. coli’
s genome is a book of wisdom. It offers hints about how life has evolved over billions of years—how complex networks of genes emerge, how evolution can act like an engineer without an engineer’s brain. Nested within
E. coli’
s genome are clues to the earliest stages of life on Earth, including the world before DNA. Those clues may someday help guide scientists to the origins of life itself.

THE TREE OF LIFE

To read
E. coli’
s palimpsest, scientists have had to figure out which parts of its genome are new and which are old. The answer can be found in the genealogy of germs. A family tree of the living strains of
E. coli
indicates that they all descend from a common ancestor that lived some 10 million to 30 million years ago. Even farther back,
E. coli
shares an ancestor with other species. Reach back far enough, and you ultimately encounter the ancestor
E. coli
shares with
all
other living things, ourselves included.

Reconstructing the tree of life—one that includes
E. coli
and humans and everything else that lives on Earth—has been one of modern biology’s great quests. In 1837, Charles Darwin drew his first version of the tree of life. On a page in his private notebook he sketched a few joined branches, each with a letter at its tip representing a species. Across the top of the page he wrote, “I think.”

The fact that species have common ancestors explains why they share many traits. As different as bats and humans may seem, we are both hairy, warm-blooded, five-fingered mammals. Darwin himself did not try to figure out exactly how all the species alive were related to one another, but within a few years of the publication of
The Origin of Species,
other naturalists did. The German biologist Ernst Haeckel produced gorgeous illustrations of trees sprouting graceful bark-covered boughs. His trees were accurate in many ways, scientists would later find. But Haeckel marred them with a stupendous anthropocentrism. To Haeckel, the history of life was primarily the history of our own species. His tree looked like a plastic Christmas tree, with branches sticking out awkwardly from a central shaft. He labeled the base of the tree
Moneran,
the name he used for bacteria and other single-celled organisms. Farther up the tree were branches representing species more and more like ourselves—sponges, lampreys, mice. And atop the tree sat
Menschen.

This view of life has been a hard one to shake. It probably had something to do with the decision to split life into prokaryotes and eukaryotes, the supposedly primordial bacteria and the “advanced” species like ourselves that evolved from them. It’s a deeply flawed view. The evolution of life was not a simple climb from low to high.
E. coli
is a species admirably adapted to warm-blooded creatures that did not emerge for billions of years after life began. It is as modern as we are.

It took a long time for a more accurate picture of the tree of life to take hold. One major obstacle was the lack of information scientists could use to determine how
E. coli
is related to other bacteria, or how bacteria are related to us. To compare ourselves to a bat, we can simply use our eyes to study fur, fingers, and other parts of our shared anatomy. Under a microscope, however, many bacteria look like nondescript balls or rods. Microbiologists sometimes classified species of bacteria based on little more than their ability to eat a certain sugar, or the way they turned purple when they were stained with a dye. It was not until the dawn of molecular biology that scientists finally got the tools required to begin drawing the tree of life. Experiments on
E. coli
helped them to recognize that all living things share the same genetic code, and the same way of passing on genetic information to their descendants. They share these things because they had a common ancestry.

In the 1970s, Carl Woese, a biologist at the University of Illinois, Urbana-Champaign, discovered a way to use those shared molecules to draw a tree of life. Woese and his colleagues teased apart ribosomes, the factories for making proteins, and studied one piece of RNA, known as 16S rRNA. Woese did his work years before scientists could easily read the sequence of RNA or DNA. So he and his colleagues did the next best thing: they sliced up
Escherichia coli’
s 16S rRNA with the help of a virus enzyme. They then cut up the 16S rRNA of other microbes and gauged how similar their fragments were to those of
E. coli.
They discovered many regions that were identical, base for base, no matter which species they compared. These regions had not changed over billions of years. The regions that had diverged revealed which species were more closely related than others.

Rough and preliminary as the results were, they upended decades of consensus. The standard classifications of many groups of bacteria turned out to be wrong. Most startling of all, Woese and his colleagues found that a number of bacteria were closer to eukaryotes than to other bacteria. They were not bacteria at all. Woese and his colleagues declared that life formed not two major groups of species but three. They dubbed the third domain of life archaea. “We are for the first time beginning to see the overall phylogenetic structure of the living world,” Woese and his colleagues declared.

Over the next thirty years, scientists built on Woese’s work, drawing a more detailed picture of the tree of life. They studied ribosomal RNA in more species. They found other genes that also made for good comparisons. They used new statistical methods that gave them more confidence in their results. They found many more species of archaea, confirming it as a genuine branch of life. Archaea may look superficially like bacteria, but they have some distinctive traits, such as unique molecules that make up their cell walls.

To measure the diversity of life, Woese and his colleagues counted up the mutations to ribosomal RNA that had accumulated in each branch of life. The more mutations, the longer the branch. The new tree was a far cry from Haeckel’s. The animal kingdom became a small tuft of branches nestled in the eukaryotes. Two bacteria that might look identical under a microscope were often separated by a bigger evolutionary gulf than the one that separates us from starfish or sponges. One look at the tree made it clear that the evolutionary history of any individual species of bacterium—
E. coli,
for example—is a complicated tale.

TREE VERSUS WEB

In the 1980s, some experts on the tree of life became worried. It was slowly becoming clear that horizontal gene transfer was not just a peculiarity of
E. coli’
s laboratory sex or the modern era of antibiotics. Genes had moved from species to species long before humans had begun to tinker with life. If genes moved too often, some scientists feared, they might make it impossible to reconstruct the tree’s branches.

To reconstruct the tree of life, scientists compare DNA from different species and come up with the most likely pattern of branches that could have produced the differences. A genetic marker shared by two species might reveal that they had a close common ancestry, one not shared by species that lack the marker. But those markers make sense only if life passes down all its genes from one generation to the next. If a gene slips from one species to another, it can create an illusion of kinship that’s not actually there.

At first, most scientists dismissed this sort of fretting. Over the course of billions of years, horizontal gene transfers were inconsequential. To find the true tree of life, scientists assumed they just had to avoid those rare swapped genes.

In later years it became possible to get a better sense of how much horizontal gene transfer has occurred by comparing genomes. The genomes of humans and other animals didn’t show much evidence of recently transferred genes. That’s not too surprising when you consider how we reproduce. Only a few cells in an animal—eggs and sperm cells—have a chance to become a new organism. And these cells have very little contact with other species that might bequeath DNA to them. (The chief exceptions to this rule are the thousands of viruses that have inserted themselves in our genomes.) But in this respect, animals were oddities. Bacteria, archaea, and single-celled eukaryotes turned out to have traded genes with surprising promiscuity. And those traded genes, some scientists argued, posed a serious threat to the dream of drawing the full, true tree of life.

W. Ford Doolittle, a biologist at Dalhousie University in Halifax, Nova Scotia, illustrated the seriousness of the threat in an article in
Scientific American
in 2000. The article includes a picture of two trees. The first shows the tree of life as revealed by ribosomal RNA, with bacteria, archaea, and eukaryotes branching off in an orderly fashion from a common ancestor. The second shows what the history of life might really look like: a tree emerging from a mangrovelike network of roots, with branches fused into a tangle of shoots. Parts of it look less like a tree than a web.