The domestication of animals and plants is the most important technological innovation during human history. This genetic transformation of wild species has occurred as humans have used individuals carrying favorable gene variants for breeding purposes. In the current issue of Nature, an international team led by researchers at Uppsala University, and including researchers from Virginia Tech, has revealed some of the secrets underlying the remarkable development of the domestic chicken.

The domestic chicken has in recent years become the most important and cost-effective source of animal protein world-wide. In the beginning of the 20th century specialized layer (egg-producing) and broiler (meat-producing) chickens were developed. The approach has been remarkably successful and has led to huge improvements in productivity.

"The strategy to study four different populations of layer chickens as well as four broiler populations allowed us to reveal genetic changes of crucial importance for chicken domestication in general as well as changes that were essential for the development of layers or broilers," says Leif Andersson who coordinated the study.

In 2004, a draft genome sequence of the chicken was established by sequencing a single female red junglefowl, the wild ancestor of chickens. The task required a major economic investment (millions of US dollars) and a large international team of scientists. In the current study the researchers have used new sequencing technologies and a modest budget to analyze pools of individuals representing eight different populations of the domestic chicken and a red junglefowl population.

"This is the first study ever where the genetic diversity within and between populations are examined across the whole genome," says Michael Zody, who did his PhD partially on this project and is now a researcher at the Broad Institute. "The new sequencing technologies allow us to address important biological questions that were impossible to study just a few years ago."

A selective sweep takes place when a favorable mutation becomes fixed in a population. This happens in all species during the course of evolution and it happens in domestic animals as a consequence of human-driven selection for favored traits. One of the most interesting findings in this study was a striking selective sweep at the TSHR gene that codes for the thyroid-stimulating hormone receptor. In vertebrates, this protein has a key role in metabolic regulation but also in determining the timing of reproduction as a response to changes in day length, a trait that is strictly controlled in most wild animals but which is drastically altered in domestic chickens that can reproduce all year around.

"Our discovery that every domestic chicken that we have studied representing populations from Sweden to China carry a mutant form of the TSHR protein strongly suggests that this genetic change was an important step in the evolution of the domestic chicken," says Leif Andersson.

Another very convincing selective sweep was observed in broiler chickens and involved the TBC1D1 gene, a gene that has previously been associated with obesity in humans and the TBC1D1 protein is involved in the regulation of glucose uptake in muscle cells.

"Our study shows that billions of broiler chickens worldwide carry a mutant form of the TBC1D1 gene and we are now very eager to identify the causative mutation at this locus and to reveal the molecular mechanism by which it impacts growth," says Carl-Johan Rubin who was responsible for the bioinformatic analysis of selective sweeps.

"Our study has direct implications for animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research since we can so effectively reveal genes associated with changes in phenotypic traits," concludes Leif Andersson.

The research team identified a gene found in all of Virginia Tech's high-growth chickens but few of the low-growth ones that appears to regulate appetite – a finding that could have ramifications for both animal and human health studies involving weight. Previous research has shown that appetite, in addition to metabolism, plays a significant role in weight gain or loss in poultry.

The team is also investigating a gene that encodes the thyroid-stimulating hormone receptor protein to determine whether domestication altered the genetic makeup of chickens thousands of years ago. If true, this would be the first time that scientists have identified a mutation in animals caused by domestication.