Although organisms have diversified remarkably through evolution, they do not exhibit unlimited variability. During evolution, the phenotypic changes do not occur at random; instead, they are directional and restricted by the constraints imposed on them. Despite the perceived importance of characterizing the unevenness of these changes, studies on evolutionary constraints have been primarily qualitative in nature. In this review, we focus on the recent studies of evolutionary constraints, which are based on the quantification of high-dimensional phenotypic and genotypic data. Furthermore, we present a theoretical analysis that enables us to predict evolutionary constraints on the basis of phenotypic fluctuation, modeled on the fluctuation-response relationship in statistical physics. The review lays emphasis on the tight interactions between experimental and theoretical analyses in evolutionary biology that will contribute to a better understanding of evolutionary constraints.
Keywords: Developmental hourglass model; Evolutionary constraints; Evolutionary fluctuation–response relationship; Microbial laboratory evolution.