A number of environmental triggers have been shown to affect the behavior of an organism's epigenome, tipping the balance between methylation or lack thereof, and thus between genes that are "off" and those that are "on." One suspected trigger is a chemical found in many plastic drink bottles, including baby bottles, called bisphenol A. In one particularly notable study, scientist Randy Jirtle and his group of researchers exposed pregnant mice to bisphenol A and watched as more of their genetically identical progeny developed into yellow, obese mice than would normally be expected (Dolinoy et al., 2007). In Jirtle's experiment, DNA methylation at the agouti gene sites was decreased by 31%. (DNA methylation was reduced on other genes as well.) These results supported the hypothesis that bisphenol A alters the action of organisms' epigenomes by removing methyl groups from DNA.

The implications of this discovery are staggering. With the rise of obesity in Americans coinciding with the widespread use of bisphenol A in everything from water bottles to dental sealants, one can't help wondering whether there is a causal connection. Yet, Jirtle himself is the first person to say that such an association cannot be definitively demonstrated until evidence shows that bisphenol A indeed affects the expression of the human genes involved in obesity.

So, how does the agouti gene cause such disparate effects in mice? It was first discovered that the agouti protein binds to a melanocortin receptor located on a mouse's skin cells, which blocks those cells from making black pigment (Lu et al., 1994). Thus, because the agouti gene is constantly turned "on" in mutant mice, the melanocortin receptor is always blocked, and the animals are yellow. Roger Cone speculated that the same type of receptor might also be present in a mouse's brain. In the same 1994 paper, he reported finding melanocortin receptors in an area of the mouse brain known to be involved in feeding behavior and body weight set point. Thus, the agouti protein appears responsible for both phenotypic differences in mouse twins: coat color and body weight.

But exactly how does exposure to bisphenol A affect both skin cells and brain cells? Through careful study, Jirtle found that the amount of DNA methylation was fairly consistent through an individual mouse's body. This result suggested that the demethylation that led to yellowness and obesity occurred in early development. Despite this suggestion, not all the mice pups that Jirtle observed grew to be unhealthy. In other words, bisphenol exposure didn't guarantee obesity in mice; rather, it simply increased the risk of developing obesity.