The hourglass and the early conservation models--co-existing patterns of developmental constraints in vertebrates

PLoS Genet. 2013 Apr;9(4):e1003476. doi: 10.1371/journal.pgen.1003476. Epub 2013 Apr 25.

Abstract

Developmental constraints have been postulated to limit the space of feasible phenotypes and thus shape animal evolution. These constraints have been suggested to be the strongest during either early or mid-embryogenesis, which corresponds to the early conservation model or the hourglass model, respectively. Conflicting results have been reported, but in recent studies of animal transcriptomes the hourglass model has been favored. Studies usually report descriptive statistics calculated for all genes over all developmental time points. This introduces dependencies between the sets of compared genes and may lead to biased results. Here we overcome this problem using an alternative modular analysis. We used the Iterative Signature Algorithm to identify distinct modules of genes co-expressed specifically in consecutive stages of zebrafish development. We then performed a detailed comparison of several gene properties between modules, allowing for a less biased and more powerful analysis. Notably, our analysis corroborated the hourglass pattern at the regulatory level, with sequences of regulatory regions being most conserved for genes expressed in mid-development but not at the level of gene sequence, age, or expression, in contrast to some previous studies. The early conservation model was supported with gene duplication and birth that were the most rare for genes expressed in early development. Finally, for all gene properties, we observed the least conservation for genes expressed in late development or adult, consistent with both models. Overall, with the modular approach, we showed that different levels of molecular evolution follow different patterns of developmental constraints. Thus both models are valid, but with respect to different genomic features.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution
  • Evolution, Molecular*
  • Gene Duplication
  • Gene Expression Regulation, Developmental*
  • Genome
  • Phylogeny
  • Zebrafish / genetics

Grants and funding

We acknowledge funding from Etat de Vaud and the Swiss National Science Foundation (ProDoc grant 1206624/1); in addition, SB was supported by the Swiss National Science Foundation (grant 31003A 130691/1) and the Swiss Institute of Bioinformatics. MR-R was supported by the Swiss National Science Foundation (grant 31003A 133011/1) and the Swiss Institute of Bioinformatics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.