Synchronizing Molecular Clocks

Charles Darwin first suggested that species change over time. The frequency of these genetic changes is described as the ticking of a "molecular clock."

In classic tales of mystery, police detectives ask suspects what they were doing on a certain day. Most people would be hard pressed to recall such incidents, unless there was something to help in the recollection. Most events, however, are not fixed in some preservable medium such as video or writing. Imagine then, how hard it must be to pin a date on something that happened long before the human race even existed.

Some parts of the Earth have preserved events of the past, of course. Bones fossilize, tree rings reflect weather events, and layers of rocks serve as templates of time, recording changes in the atmosphere or water chemistry. But our knowledge of the Earth’s history is far from complete, partly because not every event has been preserved.

The discovery of DNA opened a new record book for the history of organisms. As anyone who knows their Darwin understands, species change over time. According to the theory of molecular evolution, these changes are reflected in the genetic code. The frequency of these genetic changes can be seen as the ticking of a "molecular clock."

Molecular clocks can trace the branches of a family tree back to the original root. As two species arose from a common ancestor, changes occurred in their genomes. The more the species diverged, the greater the number of genetic differences. Counting these differences, and dividing them by the rate of genetic mutation, takes you back in time to the ancestor.

Some stunning results have come out of this technique. For instance, molecular clock data places the origin of modern humans at only 100,000 years ago, when previous estimates were of an origin one million years ago. The emergence of animals, meanwhile, has been pushed further back in time by molecular clock studies. Prior estimates placed their origin at about 600 million years ago, but according to molecular clock data it happened more than a billion years ago.

These dramatic dates give some biologists pause. Why would genes differ so much from the rock record? Why would there be a 400 million-year gap, for instance, between the genetic evidence for the emergence of animals and the first animal fossil?

The "molecular clock" method assumes that changes in DNA accumulate at approximately constant rates over time.

One explanation is that species might undergo genetic changes long before those changes are reflected in the body plan. An organism experiences a "tick" of its molecular clock, recording a change in its genome, and yet physically looks the same as one who has not.

This brings up the question of how to determine when an organism crosses the genetic line between one species and another. There can be a great deal of genetic diversity within a species, and many mutations are irrelevant since they have no discernable effect on an organism. It may take many generations before genetic changes result in what we commonly think of as two separate species. Molecular clocks help determine the genetic differences between species by tracking which genes changed over time.

But molecular clocks are based on assumptions that make some biologists uncomfortable. For one thing, the method assumes that changes in DNA accumulate at approximately constant rates over time.

While mutations in the genome of a species tend to tick away at a fairly steady rate, many genes are known to violate this clock-like trend. Proponents of molecular clocks say they can recognize such genes and remove them from molecular clock studies. This guarantees more accurate results, and the errant genes then can be studied individually in separate studies.

Blair Hedges, an evolutionary biologist with Penn State University and a leading researcher in molecular clock studies, says that no one ever claimed that all genes and all species evolve at the same rate.

"It has been well established for decades that some species evolve faster or slower than others at some genes, and perhaps even consistently fast or slow across many genes," says Hedges. "Clock methods have been developed over the years to account for those differences."

Another point of contention is how molecular clocks are calibrated. The genetic information for a molecular clock study is gathered from living species, and the gene sequences are plotted on a graph with evolutionary events that are well established in the fossil record. This technique helps determine the tempo of a particular molecular clock.

Vertebrate fossils have been used to calibrate many molecular clock studies of animals.

Vertebrates are common in the fossil record, since bone preserves better than soft tissue. Vertebrate fossils therefore have been used to calibrate many molecular clock studies of animals.

But more ancient organisms don’t have much of a fossil record. For these soft-bodied organisms, researchers extrapolate a molecular rate of change from the vertebrate calibrations, assuming that the clocks have continued at a comparable pace through time. This extrapolation makes many biologists wary.

The fossil record prior to the Cambrian explosion (around 600 million years ago) is extremely poor. Several scientists have used invertebrate microfossils as calibration points, but this still does not take us beyond the Cambrian era. The lack of Precambrian fossil calibration points is a continuing problem for molecular clock studies involving ancient organisms.

As molecular clock studies become more complete and complex, doubt is being cast on earlier findings. For example, fish and birds living in cold environments were thought to have slower molecular clocks (slower rates of change) than other vertebrate animals.

Yet in a study published last year in the journal Science, David Lambert of Massey University in New Zealand found that the genome of Antarctic penguins has evolved faster than was first reported. Examining 6,000 year-old DNA from Adélie penguins, he found that the rate of genetic mutation is about two to seven times faster than previous estimates.

Because Adélie penguin colonies return to the same nesting grounds every year, one location can have layers of bones dating far back in time. Lambert’s team members collected and dated 96 bones from various layers and gathered 300 blood samples from living birds. Because he had access to an entire spectrum of bones dating back 6,000 years, Lambert’s study differs from previous efforts to determine rates of genetic change. Previous studies had to be satisfied with just one or two generations, or with genetic information from organisms separated in time by millions of years.

"It seems clear that using a different approach to the traditional one, we get a different answer to the question of evolutionary rates," says Lambert. "So in some sense the work must bring into question earlier rates."

While molecular clock dating remains somewhat controversial, many scientists believe that the method will ultimately prove to be important in understanding evolution.

"Evolutionary biologists essentially have been trying to answer two central questions for a long time," says Lambert. "One is, ‘what are the relationships among life forms?’ In other words, what is the tree of life? Secondly, they have been trying to put a time scale on the tree. Our work, and studies like it, helps with the second goal."

What’s Next

Lambert now has carbon dates of Adélie penguins going back 37,000 years. He also hopes to also use ancient DNA to measure evolutionary rates in Antarctic fish, kiwi, tuatara and humans.

Hedges is using molecular clocks from many genes to pin down dates of astrobiological interest, such as the origin of cyanobacteria and oxygen, the origin of eukaryotes, and the rise of complex multi-cellular life.

Related Web Pages

Molecular Evolution
David Lambert
Blair Hedges
Adélie penguins