It has long been suggested that organ-ismal evolution is limited by con-straints on embryonic development that prevent certain changes from being tolerated. A new study using zebrafish and mice has explored how developmental constraints deter-mine which genetic changes can be tolerated and therefore contribute to evolution.

Previous studies have examined developmental constraints on evolu-tionary genetic change in vertebrates. However, these studies might not give a reliable picture of the pattern of constraint because of issues such as coarse divisions of developmental stages into simply ‘early’ and ‘late’, and small sample sizes in terms of the number of genes analysed.

Roux and Robinson-Rechavi first built up gene expression profiles for 26 mouse and 14 zebrafish

developmental stages using existing data on thousands of genes from EST counts and microarray analyses, respectively. They then examined the likelihood that two types of genetic change — loss of function and duplication — are tolerated for genes expressed at each stage.

In terms of loss of function, severe phenotypes reported from mutagenesis and morpholino studies were used to indicate probable evolu-tionary constraint. In the case of gene duplication, the expression of gene duplicates that have been retained following ancestral genome duplica-tion was examined; the retention of a duplicate suggests that doubling the gene dose has been tolerated during evolution. For both species, a clear trend was seen in which the early stages of development are the least tolerant of mutations.

Following this early peak, constraint seems to decline steadily throughout the rest of development.

Notably, these findings contrast with the ‘hourglass’ model that is often used to describe vertebrate developmental constraint that is seen at the morphological level. Here, maximal constraint is seen at a mid- developmental time point, before and after which evolution has greater flex-ibility to act. As the authors point out, our ability to make sense of differences in timing of constraint at the two levels will require an increased understand-ing of how mutation gives rise to ontogenic change during evolution.

Louisa Flintoft

Original research PaPer Roux, J. & Robinson-Rechavi, M. Developmental constraints on vertebrate genome evolution. PLoS Genet. 4, e100031 (2008)

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NATuRE REvIEwS | Genetics volumE 10 | FEbRuARy 2009

Nature Reviews Genetics | AoP, published online 13 January 2009; doi:10.1038/nrg2530

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