A maternal effect shapes early-life adaptive body size variation in house mice

Almost all phenotypic variation is mediated by a combination of genetic and environmental effects. Importantly, the balance of these effects can fluctuate over an organism’s lifespan, with the maternal environment being particularly important during early life, especially in mammals. Using house mice as a model, we combine behavioral, molecular, and quantitative genetic approaches to understand how genetic and maternal variation together shape phenotypic divergence in a classic example of morphological adaptation. Temperate house mice are larger than tropical house mice, conforming to Bergmann’s rule. We find that cross-fostering leads to pronounced weight restriction in cold-adapted, large-bodied mice, revealing an important effect of maternal environment. We then describe the molecular underpinnings of genetic and maternal influences on weight by identifying both the genetically- and maternally-controlled differences in gene expression in liver, a key tissue regulating growth. Maternally plastic expression variation is largely controlled in trans -, while stable, genetic variation is mediated in cis- . Additionally, we link maternally-controlled expression variation in growth-restricted mice to known nutrient deficiency signaling pathways. Finally, we identify candidate loci underlying the genetic basis of adaptive body size divergence from a combination of selection scans in wild populations and cis -regulated genes that overlap QTL identified in a mapping panel of temperate and tropical mice. Collectively, these results provide insight into how genetic and environmental forces influence adaptive phenotypic divergence in the context of a critical developmental window.