Developmental Constraints on Vertebrate Genome Evolution

Constraints in embryonic development are thought to bias the direction of evolution by making some changes less likely, and others more likely, depending on their consequences on ontogeny. Here, we characterize the constraints acting on genome evolution in vertebrates. We used gene expression data from two vertebrates: zebrafish, using a microarray experiment spanning 14 stages of development, and mouse, using EST counts for 26 stages of development. We show that, in both species, genes expressed early in development (1) have a more dramatic effect of knock-out or mutation and (2) are more likely to revert to single copy after whole genome duplication, relative to genes expressed late. This supports high constraints on early stages of vertebrate development, making them less open to innovations (gene gain or gene loss). Results are robust to different sources of data—gene expression from microarrays, ESTs, or in situ hybridizations; and mutants from directed KO, transgenic insertions, point mutations, or morpholinos. We determine the pattern of these constraints, which differs from the model used to describe vertebrate morphological conservation (“hourglass” model). While morphological constraints reach a maximum at mid-development (the “phylotypic” stage), genomic constraints appear to decrease in a monotonous manner over developmental time. Because embryonic development must proceed correctly for an animal to survive, changes in evolution are constrained according to their effects on development. Changes that disrupt development too dramatically are thus rare in evolution. While this has been long observed at the morphological level, it has been more difficult to characterize the impact of such constraints on the genome. In this study, we investigate the effect of gene expression over vertebrate developmental time (from early to late development) on two main features: the gravity of mutation effects (i.e., is removal of the gene lethal?) and the propensity of the gene to remain in double copy after a duplication. We see that both features are consistent, in both zebrafish and mouse, in indicating a strong effect of constraints, which are progressively weaker towards late development, in early development on the genome.