Looking for Life Beyond Earth
Can You Relate?

"We have an amazing world," said Janet Siefert, Keck fellow in molecular biology at Rice University. "Full of extravagant beauty and diversity."

The projection screen above her head flashed a series of images: of tigers, and swordfish, and the bluebonnets of her native Texas, whose balmy winter temperatures Siefert had left to give the second Frontiers of Science lecture last January.

"But there's another world that underpins everything that goes on," she said, and the focus suddenly shifted. Single-celled microorganisms now filled the screen. Diatoms, Euglena, paramecia. Giardia. "These are eukaryotes," she said. "Very closely related to humans."

Eukaryotes, she explained, are distinguished from other microbes by their complexity: the internal membranes, the machine-like organelles, and, most important, a core nucleus. "It's this structure that allows for differentiated cells, and lets multicellar organisms arise."

King of the planet?

All the world's animals are eukaryotes, she noted, and all the insects and the plants too, not to mention fungi and algae. Among animals alone, by far the smallest subset, there are over a million species. "But eukaryotes are only a small fraction of the biological diversity on Earth."

A kind of family tree called a phylogeny helps to make the point. On screen, this tree of life consists of three main stems emerging from a sturdy trunk. The first, labeled "eukaryotes," looks stunted, dwarfed.

The other two branches, much larger and fuller, are the prokaryotes: bacteria and archaeabacteria. A more humble class of organisms, these. No impressive innards: no mitochondria, no nuclei. No internal membranes enforcing structure. "They look very simple," Siefert admitted, "but they have remarkable biological diversity." Not only do they have us badly outnumbered; it seems that we need them more than they need us. "If you took away the eukaryotes," Siefert said, "you'd still have a living planet. If you take away the bacteria and archaea, everything crashes."

She showed us some common bacteria: helicobacter (the cause of most ulcers), E. coli, salmonella. And some that are not so common. Thiomargarita, the "scuba-tank" bacteria (so-called because of its ability to store nitrate for respiration), is "one-fifth the size of a bumblebee," a true giant among its peers, one billion of whom (on average) can fit in the eye of a needle. Size ranges aside, she said, "They all look pretty similar. They all have a similar morphology."

So also with the archaea. "These are very interesting organisms, with amazing biochemistry," Siefert said. "They grow in strange environs: at the bottoms of rice paddies, where there's no oxygen; in highly acidic hotsprings; in hydrothermal vents at the bottom of the sea. They can live almost anywhere. But they are boring to look at."

The point is not merely aesthetic. Their similarity, Siefert said, makes these organisms hard to tell apart -- and telling them apart is the first step to creating a more complete, and more accurate, family tree. For Siefert, an accurate tree, or phylogeny, is the key to reconstructing the early evolution of life on Earth.

Establishing relationships demands comparisons. And making comparisons requires a yardstick, something common to every living organism. But what to choose? Prokaryotes don't have noses, or feathers, or feet, to lend them character. They do, however, have DNA -- and RNA, too. More specifically, they, like every organism on Earth, have ribosomes.

A ribosome is a maker of proteins: A sub-unit of RNA that reads the string of bases that makes up a genetic code and translates it into whatever the cell needs. "An incredible machine," Siefert called it. This machine itself has two sub-units. And, as it happens, the gene that codes for the smaller of the ribosome's sub-units, called 16S in prokaryotes and 18S in eukaryotes, makes a great universal point of comparison. It is easy to get. And, Siefert emphasized, "is found in every single living organism."

The process, then, is straightforward: Take the 16S genes from any two organisms; compare the sequence of bases in each. The more differences in the sequence, the farther apart on the family tree the two organisms belong.

Humvees and Cadillacs

"If I gave you a truck, a Humvee, and a Cadillac," she said, "and asked you to find out what a Model T must have looked like, what would you do? You'd take away everything those three vehicles didn't have in common, and you'd look at what's left. This is exactly what we do. If you can compare the entire genetic blueprint of an organism with that of another one, take away everything that's not common, the idea is that what's left must be what was in a common ancestor."

In 1996 evolutionary geneticists used this approach to conclude that the "minimal" genome for an ancestor that could have given rise to all of life would have to include at least 256 genes. (Yeast, a fungus, has 5,000 genes; humans have roughly 100,000.) The current debate, Siefert said, is over that murky early period before the three present-day domains emerged. How exactly did the bacteria, archaea, and eukaryotes take shape? And how did eukaryotes evolve their complexity?

Siefert showed us a timeline: the origin of life marked at 3.9 billion years ago, the earliest known fossil cells at 3.8. "Already at this point," she said, pointing to the latter, "you've got a very sophisticated organism, with ribosomes, protein-making machinery, structural molecules. How did it become so miraculously complex in so short a time?"

Unlocking this mystery won't be easy. "Genomics and phylogeny," Siefert said, "can tell us a lot about the evolution of life from 3.8 billion years ago to the present. Getting back beyond that is trickier." As for discovering life's origin, "We don't even know how to define it." Did life begin, as some suggest, with that first biochemical reaction, the synthesis of amino acids? With the pre-cellular molecules -- capable of copying themselves and passing on their genetic information -- that would have populated an RNA world?

"As far as I'm concerned," Siefert said, "to call it life you also need that compartmentalization. You need a cell."

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