Evolutionary Developmental Basis of Adaptation

Frank Chan

FrankChanNov2012-05 crop2
  • PhD in the Department of Developmental Biology, Stanford University, 2003-09
  • Postdoctoral training, Max Planck Institute for Evolutionary Biology, Plön, 2009-12
  • Max Planck Research Group Leader at the FML since 2012

Research Interest

The genome is in constant evolution. Despite this on-going change, the genome also has to maintain essential functions. Discovering the evolutionary process underlying genome evolution is thus a central goal not only in evolutionary genetics, but also in medicine. Using the house mouse as our model organism, we aim to connect molecular mutations to their phenotype consequences and track their fate through evolution.

Selection experiments represents some of the most powerful tools to directly observe evolution in action. We have an on-going collaboration with Dr. Campbell Rolian at the Univ. of Calgary to study his “Longshanks” selection lines. By subjecting mouse to twenty generations of strong selection for increased tibia length, he was able to generate mice with 16% longer tibia in two replicated selection lines than their random-bred relatives. We have sequenced the entire selection experiment (>2000 individuals), in order to reconstruct the population genomics response to selection with unprecedented resolution. Together with Dr. Nick Barton at IST Austria, we will study the selection response from multiple angles, ranging from trait mapping, population genomics, theory to developmental genetics. The Longshanks selection experiment combines quantitative, developmental and population genetics and offers a unique opportunity to study how the genome responds to strong selection in a model paradigm.

Taking our approach beyond intra-specific variations, we have pioneered an innovative system to directly perform genetic mapping between species in vitro using mouse embryonic stem cells (“HybridMiX”). By creating interspecific hybrids between mice with increasing divergence, we can study how traits evolve between rodent species. Our in vitro cross approach creates “Impossible Hybrids” – advanced recombinant cell lines that circumvent conventional species barriers. This project uses the latest functional genomics techniques like RNA/ChIP-seq and chromosome conformation capture, as well as microfluidics and tissue engineering approaches to address fundamental evolutionary genetics questions.

The ultimate goal of our research is to understand how evolution has shaped gene regulatory networks to be tightly interwoven, yet still allow flexible response to allow rapid adaptation.

  • Frank chan Fig 1 2016
    click to enlarge

Evolution in action. The Rolian Lab has performed selective breeding in a Longshanks line for 20 generations, leading to a dramatic increase of 16% in tibia length. By sequencing the entire pedigree of the selection experiment, we will reconstruct how individual alleles spread through the population and how the genome change in response to selection. Data: Campbell Rolian and Frank Chan

  • Frank Chan Fig2 2016 01
    click to enlarge

HybridMiX: for the first time we can now directly study the genetic changes between species by performing “in vitro crosses” between evolutionarily distant mouse species. By studying these “impossible hybrid” cell lines using genomics, organ-on-a-chip and organoid techniques we aim to reveal how gene regulatory networks change through six million years of evolution.

Available PhD Projects

Project 1: Longshanks mice: population genomics of response to selection in an “evolve and resequence” experiment.

Project 2: Impossible hybrids: dissecting the genetic basis of species differences using in vitro crosses in the mouse.

Selected Reading

1) Chan YF, Jones FC, McConnell E, Bryk J, Bünger L, Tautz D (2012) Parallel selection mapping using artificially selected mice reveals body weight control loci. Current Biology 22, 794-800.

2) Jones FC*, Grabherr MG*, Chan YF*, Russell P* et al. (2012) The genomic basis of adaptive evolution in threespine sticklebacks. Nature 484, 55-61. *equal contribution

3) Chan YF, Marks ME, Jones FC, Villarreal Jr G et al. (2010) Adaptive evolution of pelvic reduction in sticklebacks by recurrent deletion of a Pitx1 enhancer. Science 327, 302-305.