Integrating mechanistic and evolutionary views on phenotypic integration through hormonal pleiotropy

Organismal biologists have studied phenotypic integration from diverse perspectives that span molecular, cellular, physiological, and developmental mechanisms up through evolutionary patterns. Nonetheless, integration across these scales is rare, such that studies of mechanism can be difficult to link to evolutionary dynamics, and vice versa. Here, we integrate mechanistic and evolutionary perspectives on phenotypic integration through hormonal pleiotropy, which occurs when one hormone influences the expression of multiple traits. We focus on trait covariances as unifying measures of phenotypic integration that can be quantified at multiple scales of biological organization and linked to evolutionary dynamics through associated measures of genetic covariance. Drawing from our work on steroid hormones in Anolis and Sceloporus lizards, we illustrate experimental approaches for quantifying the hormonal regulation of phenotypic integration at both organismal and transcriptomic scales. By combining these experimental approaches with quantitative genetic theory and breeding designs, we illustrate how hormonal pleiotropy structures not only phenotypic integration, but also the underlying genetic variances and covariances that shape evolutionary responses to selection. We also explore how estimates of genetic variance and covariance in phenotypic responsiveness to a hormonal signal can reveal constraints imposed by hormonal pleiotropy that may shape the evolution of integrated phenotypes. Finally, we review recent work showing that responsiveness to testosterone can evolve at the transcriptomic level to produce divergent patterns of hormonal pleiotropy and phenotypic integration in closely related species.