Looking for Life Beyond Earth
A Question of Timing

"A phylogenic tree," Blair Hedges began his Frontiers of Science lecture, "shows the relationships between organisms. It shows that we're closer to chimpanzees than we are to gorillas -- and that birds, which are warm-blooded, are actually closer to lizards than they are to mammals."

But a phylogenetic tree, added Hedges, an associate professor of biology at Penn State, cannot show us how things got that way. To follow evolution's path, you need to put a stopwatch on the stages. You need to know when.

Enter DNA

The chemist Linus Pauling, then at Cal Tech, first proposed a molecular clock back in 1962. James Watson, Francis Crick, and Maurice Wilkins at Cambridge University had recently revealed the secrets of DNA's structure -- the celebrated double helix -- and geneticists were busily decoding the sequences of nucleotides, or bases, that add up to genes.

"As soon as enough sequences were generated that you could make comparisons between species," Hedges said, "people started recognizing that molecular data" -- the order of bases in a given strand of DNA -- "are different from morphological data" -- that is, an organism's gross characteristics, like noses, feathers, and feet. While morphology tends to evolve in spurts, dependent on the forces of natural selection, molecular change happens at a fairly constant rate, at least when measured over hundreds of millions of years.

Within a given gene, Hedges said, base pairs are constantly being damaged or otherwise altered, and only sometimes being repaired. "Quite a few of these changes will be deleterious. They will negatively affect important functions of the gene, turn it off, cause the organism to die." Other mutations will confer some evolutionary advantage. The majority, however, will have no effect whatsoever. These "neutral" changes are made possible by a redundancy built into the system: With four "flavors" of bases -- A, T, G, and C -- and a string of three base pairs required to make an amino acid, there are 64 possible trios of base pairs, to form only 20 amino acids.

Neutral changes are shifts in position, not ingredients; a C-G pair replaces a G-C, say, but in essence the amino acid is the same.

"If it doesn't cause a change in the amino acid," Hedges said, "natural selection can't ‘see' it, so it doesn't have an effect in terms of evolution."

These changes, in other words, are completely random. And while that means they aren't completely regular -- they tend to happen in clusters, Hedges said -- over the long haul a given gene evolves at a constant rate. If you know that rate, and you know that the gene is present in a pair of organisms, counting the number of changes that have occurred in each will yield the length of time since the two diverged from a common ancestor.

To make sure a DNA clock is accurate, Hedges said, you have to calibrate it. The best calibration so far -- "the closest thing we have to proof that molecular clocks actually work" -- comes from studies of influenza. "Thirty or 40 years ago, people started freezing flu virus for later study. When some of these viral particles were thawed out in the 1980s and sequenced, researchers compared their DNA sequences to those of today's flu strains, and found a significant number of nucleotide changes. They knew exactly the number of years since those viruses had been frozen, so they could do a precise comparison."

Answering big questions

DNA clocks have been used to clarify some of evolution's biggest questions. To trace out the early history of the vertebrates, for instance, Hedges and his collaborators have looked at 7,000 different genes, and some 300 species, using for a calibration point the separation of birds and mammals around 310 million years ago. ("This is a really good split," Hedges said. "There's an excellent fossil record, based on bone characteristics.") The results are encouraging. "We've come up with divergence times for early splits in vertebrates that match up well: amphibians from reptiles and mammals at 360 million years ago; trout and salmon from other fishes, 450 million. . . . For the split between humans and chimps we got 5.5 million, which is close to the time assumed by most anthropologists."

Other findings are more controversial. Take the Cambrian "explosion," sometimes known as Evolution's Big Bang. The fossil record is rich with specimens from the dawn of the Cambrian period, 540 million years ago, Hedges said. Beyond that boundary, animals, and many plants, are virtually absent. "What it suggests is a tremendous proliferation of these higher species all at once." In a few short millions of years, according to the bones, Earth's biological diversity zoomed from next to nothing to virtually all its modern variety.

But molecular data collected in labs around the world over the last 20 years, Hedges said, tell a different story. According to the DNA, "Animals diverged one billion years ago, not 540 million." What could account for a 500-million-year gap? "Maybe animals were smaller, microscopic even," Hedges suggested. "Maybe they were soft-bodied, and therefore rapidly decaying. Right around the Cambrian border animal tracks are very small. Then they get much larger. Maybe there was an increase in size right at that boundary.

"Most paleontologists don't accept these dates," he acknowledged. "Only time and the weight of accumulating evidence will show who's right." It is already clear, however, that molecular clocks can be a powerful tool for understanding the effects of the environment on biological evolution. "Once you have a time tree of evolution," Hedges said, you can compare it against documented events in Earth's history, like the period of heavy asteroid bombardment between 4.4 and 4.0 billion years ago, or the steady rise in atmospheric oxygen to its present 18 percent.

The latter information will come in handy when, in a few years, we are able to detect the atmospheres of planets outside the solar system, he told us. "We will be able to find out whether there is oxygen in those atmospheres, and how much. And if there is a relationship between the level of oxygen present and the rise of life, then we can use that information to better predict the possibility of life elsewhere."

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