The genetics of pigmentation in beach mice

They looked at some mice in Florida, some of which have very light pigmentation, did crosses etc..., examined 11 candidate pigmentation genes (for mice) , did linkage and QTL analysis, and found a strong effect of MC1R and the agouti signaling protein. Most interestingly, they go into how they think the genes interact. (gene expression vs. coding region mutations, and epistasis)

some interesting parts from the conclusion:

Our results also have several implications for understanding the genetic basis of adaptation. First, this subspecific difference in color pattern is produced by a few interacting genes of large effect, supporting the idea that adaptations can involve relatively few genes rather than, as is often believed, many genes of small effect.

and,

These results support the idea that adaptation is not necessarily driven largely by cis-regulatory changes [29,30] or by (semi) dominant alleles. Third, we show that the nature of epistasis between Mc1r and Agouti in wild populations does not mirror that seen in the laboratory, suggesting that one should be cautious not only about extrapolating the genetics of laboratory strains to evolution in nature, but also about inferring the directionality of biochemical pathways from patterns of gene interactions. Finally, most genetic studies of morphological change have concentrated on the loss of phenotypic traits through loss-of-function mutations (e.g., reduced armor in stickleback fish [33,34], absence of wing spots in Drosophila [35], and lack of pigment in cavefish [36]). This study provides a novel example of how adaptation can result from mutations involving a gain of function.

Adaptive Variation in Beach Mice Produced by Two Interacting Pigmentation Genes

Cynthia C. Steiner, Jesse N. Weber, Hopi E. Hoekstra

PLoS Biology early online Aug 14, 2007

Abstract: Little is known about the genetic basis of ecologically important morphological variation such as the diverse color patterns of mammals. Here we identify genetic changes contributing to an adaptive difference in color pattern between two subspecies of oldfield mice (Peromyscus polionotus). One mainland subspecies has a cryptic dark brown dorsal coat, while a younger beach-dwelling subspecies has a lighter coat produced by natural selection for camouflage on pale coastal sand dunes. Using genome-wide linkage mapping, we identified three chromosomal regions (two of major and one of minor effect) associated with differences in pigmentation traits. Two candidate genes, the melanocortin-1 receptor (Mc1r) and its antagonist, the Agouti signaling protein (Agouti), map to independent regions that together are responsible for most of the difference in pigmentation between subspecies. A derived mutation in the coding region of Mc1r, rather than change in its expression level, contributes to light pigmentation. Conversely, beach mice have a derived increase in Agouti mRNA expression but no changes in protein sequence. These two genes also interact epistatically: the phenotypic effects of Mc1r are visible only in genetic backgrounds containing the derived Agouti allele. These results demonstrate that cryptic coloration can be based largely on a few interacting genes of major effect.