Digging Deep in the DNA

Hopi E. Hoekstra is standing in the attic of Harvard’s Museum of Comparative Zoology among horns and pelts, an elephant skin under a table here, giraffe parts over there.

She is handling lumpy pieces of something that looks like molded Styrofoam and that seems entirely out of place.

One has a long handle, like a cudgel. Another is shorter.

“It looks like a little sock,” she says, holding it up for a reporter to inspect.

The sock and cudgel do belong in the museum, however, every bit as much as the antlers and skins. They are key parts of a research program that is helping unlock one of biology’s elusive secrets — how genes control complicated behavior.

Each is a cast of a deer mouse burrow, and since each species has its own characteristic burrow, these lumpy molds embody inherited behaviors. Length, volume and shape are easily measured.

And that data, partly drawn from the field and partly from the lab, once combined with crossbreeding and advanced DNA analysis, may allow Dr. Hoekstra, an evolutionary geneticist, and her colleagues to trace the architecture of a mouse burrow right back to the genes.

Two weeks ago, in the journal Nature, Dr. Hoekstra and two colleagues — Jesse Weber, now a postdoctoral researcher at the University of Texas, Austin, and Brant Peterson, a postdoctoral researcher in Dr. Hoekstra’s lab — reported on a major step toward that goal. They identified four regions of DNA that help control burrow design: three for length and one for the presence or absence of an escape tunnel.

Their report was hailed by other scientists as an elegant and inventive piece of research. Cori Bargmann, at Rockefeller University, who studies the neurobiology and genetics of behavior in nematodes, said, “I think it’s a really exciting paper.”

“The genetics are beautiful,” Dr. Bargmann added, “But it is only the beginning.”

Now comes the hunt for the genes themselves, and perhaps even the biochemical pathways that show, step by step, how a DNA blueprint is transmitted to the scrabbling paws of a tiny mouse and translated into a hide-out from foxes, hawks and other predators.

The investigation of the genetics of behavior is a huge scientific enterprise, with great progress being made in a variety of species — roundworms, fruit flies, lab mice, sticklebacks. {snip}

Dr. Bargmann said she was impressed at Dr. Hoekstra’s success in unpacking the behavior into modules, a result that adds to the likelihood of one day finding simple genetic controls underlying the mystifying diversity of natural behavior patterns. The extraordinary variety of animal body shapes, after all, has been found to grow out of a relatively few master control genes.

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Other scientists who have watched her [Dr. Hoekstra’s] career are hopeful, but aware of the pitfalls. Gene E. Robinson at the University of Illinois at Urbana-Champaign, who has used honeybees to study social behavior, praised her “exciting, pathbreaking work” and said, “It will be hard to get to the genes, but not impossible. She has established a powerful experimental system.”

Dr. Bargmann at Rockefeller said “genetics and genomics tools developed over the past five years” are making it easier to get from a region of DNA down to one of the hundreds or more genes in that region.

But she added, “The hardest thing about studying natural traits is that endgame.”