Maternal Expression Relaxes Constraint on Innovation of the Anterior Determinant, bicoid

The origin of evolutionary novelty is believed to involve both positive selection and relaxed developmental constraint. In flies, the redesign of anterior patterning during embryogenesis is a major developmental innovation and the rapidly evolving Hox gene, bicoid (bcd), plays a critical role. We report evidence for relaxation of selective constraint acting on bicoid as a result of its maternal pattern of gene expression. Evolutionary theory predicts 2-fold greater sequence diversity for maternal effect genes than for zygotically expressed genes, because natural selection is only half as effective acting on autosomal genes expressed in one sex as it is on genes expressed in both sexes. We sample an individual from ten populations of Drosophila melanogaster and nine populations of D. simulans for polymorphism in the tandem gene duplicates bcd, which is maternally expressed, and zerknüllt (zen), which is zygotically expressed. In both species, we find the ratio of bcd to zen nucleotide diversity to be two or more in the coding regions but one in the noncoding regions, providing the first quantitative support for the theoretical prediction of relaxed selective constraint on maternal-effect genes resulting from sex-limited expression. Our results suggest that the accelerated rate of evolution observed for bcd is owing, at least partly, to variation generated by relaxed selective constraint.Synopsis: How do novel structures and functions originate? This question has proven more difficult to answer than the question of how existing structures are refined to better suit the environment. Evolution by natural selection explains the latter. Ironically, it is the power of natural selection to maintain genes that are suitable for their current roles that also works against the evolution of entirely new traits. The conservation of genes controlling the early stages of embryo development, from worms, to flies, to humans, is a famous example of natural selection's power to constrain evolution and thwart the spread of evolutionary novelties. However, the gene determining which end of the fly embryo becomes the head has a relatively recent origin. How did this gene, bicoid, escape purifying selection and take on a novel function? The authors investigate the hypothesis that because bicoid is expressed only in females it experiences only half as much constraint as a gene expressed in both sexes. Comparing sequences of bicoid with its duplicate gene zerknüllt, which retains expression in both sexes, the authors show that, as expected, the variation in bicoid is twice that of zerknüllt. The findings suggest that relaxed constraint is an important step in the origin of novel function.