Scientists at the University of Chicago have created the first genetically modified animals containing reconstructed ancient genes, which they used to test the evolutionary effects of genetic changes that happened in the deep past on the animals’ biology and fitness.
The research, published early online in Nature Ecology & Evolution on Jan. 13, is a major step forward for efforts to study the genetic basis of adaptation and evolution. The specific findings, involving the fruit fly’s ability to break down alcohol in rotting fruit, overturn a widely-held hypothesis about the molecular causes of one of evolutionary biology’s classic cases of adaptation.
“One of the major goals of modern evolutionary biology is to identify the genes that caused species to adapt to new environments, but it’s been hard to do that directly, because we’ve had no way to test the effects of ancient genes on animal biology,” said Mo Siddiq, a graduate student in the Department of Ecology and Evolution at the University of Chicago, one of the study’s lead scientists.
“We realized we could overcome this problem by combining two recently developed methods—statistical reconstruction of ancient gene sequences and engineering of transgenic animals,” he said.
Until recently, most studies of molecular adaptation have analyzed gene sequences to identify “signatures of selection”—patterns suggesting that a gene changed so quickly during its evolution that selection is likely to have been the cause. The evidence from this approach is only circumstantial, however, because genes can evolve quickly for many reasons, such as chance, fluctuations in population size, or selection for functions unrelated to the environmental conditions to which the organism is thought to have adapted.
Siddiq and his advisor, Joe Thornton, PhD, professor of ecology and evolution and human genetics at the University of Chicago, wanted to directly test the effects of a gene’s evolution on adaptation. Thornton has pioneered methods for reconstructing ancestral genes—statistically determining their sequences from large databases of present-day sequences, then synthesizing them and experimentally studying their molecular properties in the laboratory. This strategy has yielded major insights into the mechanisms by which biochemical functions evolve.
Thornton and Siddiq reasoned that by combining ancestral gene reconstruction with techniques for engineering transgenic animals, they could study how genetic changes that occurred in the deep past affected whole organisms-their development, physiology, and even their fitness.