New research has classified vertebrate evolution in relation to periods of evolution marked by changes in specific kinds of genes.

As animals evolved out of the primordial ooze, their bodies grew increasingly complex. While it’s obvious from simply looking at fish, mice, and cows that major differences exist in their body shape, it’s been rather difficult for scientists to pinpoint the kinds of genetic changes that propelled such diversity. New research by Howard Hughes Medical Institute scientists has classified vertebrate evolution in relation to “genetic epochs,” periods of evolution marked by changes in specific sets, or kinds, of genes.

“There’s a fundamental question about how the different animals on the planet evolved to have so many different capabilities, body plans, shapes, and behaviors,” says David Haussler, the HHMI investigator who headed up the study. “But it’s not been clear what types of functional changes in the DNA are driving these species forward, and whether it’s the same kinds of changes occurring over the millennia or whether there are different epochs of evolution.”

There’s a fundamental question about how the different animals on the planet evolved to have so many different capabilities, body plans, shapes, and behaviors.

David Haussler

Haussler, a professor of biomolecular engineering at the University of California, Santa Cruz, and his colleagues analyzed both how many and which types of genes evolved since the vertebrates diverged from their last common ancestor 650 million years ago. Graduate student Craig Lowe used extensive computational analyses to pick apart some of the most well-sequenced vertebrate genomes--human, cow, mouse, medaka fish, and stickleback fish. Lowe was looking for changes to the regulatory sequences of DNA. These sequences are important because they control when and how genes are expressed. Accumulating evidence suggests that changes to regulatory DNA—ather than to genes themselves—have been the major drivers of evolutionary change.

Once Lowe found the changes—millions of them—he predicted, based on proximity, which gene was most likely under the control of the affected regulatory region. He then catalogued the changes according to the kinds of genes they regulated. The team’s results, published August 19, 2011, in the journal Science, describe three separate eras of genetic evolution. The first—in which the new regulatory mutations occurred near genes involved in guiding embryonic development and setting the body plan—dates to between 600 and 300 million years ago. “More so than any other type, these were the genes evolution was fiddling with in the early days, and that’s consonant with what other studies have found,” Haussler says. “But the surprising thing is that this trend goes away.”

Right around 300 million years ago, about the time that mammals split from birds, the researchers found a shift in emphasis: Across all five species whose genomes they studied, they found that more mutations began to affect the genes that regulated cell-to-cell signaling. “Cells had been talking with each other since our common ancestor with sea sponges. But somehow natural selection got more interested in that process during this period,” Haussler says. The effect could be seen both in water (stickleback and medakas) and on land (cow, mouse, and human). Since those groups of animals had diverged long ago, Haussler notes that despite the similarities in the types of changes their genomes accumulated, “It had to have been a completely independent process.”

The most recent cluster of changes occurred around 100 million years ago. Haussler, Lowe, and their colleagues only had good comparative data for mammals, but could still pinpoint a distinct change in evolutionary emphasis. During this era, the effects of the sequence changes shifted from extracellular to intracellular, more frequently influencing the activity of genes involved in cells’ internal signaling pathways.

“It’s a subtle change in emphasis—it’s not as if one stopped and another started,” Haussler says. “But the molecular and cellular functions that evolution is tinkering with have changed during vertebrate evolution. It’s tinkering with the different parts of the cellular processes that drive life.”

The researchers then homed in on a trait that is specific to mammals: hair. Several hundred genes are known to be involved in hair production, enabling a robust statistical analysis of the trait’s genetic evolution. Sure enough, right around the time mammals split from birds, the rate of regulatory innovations around those genes picked up. The analysis showed that the surge in genetic diversity in these regions peaked at 250 million years ago, when mammals were beginning to hit their evolutionary stride. “We were really pleased to see this because it shows that, for a very specific process, the phenomenon we’re measuring makes sense,” Haussler says.

Natural selection drove the creation of humans, whales, sharks, parrots, panthers, bats—dramatically different species with complex capabilities. As they diverged, certain evolutionary processes may have been working in parallel. “Maybe the same things happened in the ocean as on land. Maybe there’s a natural progression from early tinkering with body plans to adjusting how cells talk to each other, and then on to how signals are processed within the cell,” Haussler says.

The study is just the first piece of a larger investigation into the changes that have driven vertebrate evolution—an early hint of revelations to come. Haussler is one of the leaders of the Genome 10K Project, in which he and others aim to sequence 10,000 different vertebrate species. “There’s so much more to be told, so much more granularity, so many more beautiful and mysterious events that have happened over the last half billion years,” he says. “The long, long road to humans and other magnificent animals is an unbelievable story waiting to be told.”

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