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Molecular and Developmental Basis of Adaptation

Frank Chan

Frank Chan

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

Research Interest

Organisms exhibit an enormous diversity of adaptations ranging from molecular machinery to social organization. We are interested in how complex adaptations are encoded in the vertebrate genome. Using the house mouse as our model organism, we aim to uncover the molecular innovations that allow mice and diverse mammals to crawl, swim and fly their way into various adaptive niches.

Advances in genomics and transgenics provide an unprecedented opportunity to investigate the nature of adaptive mutations at the molecular level. We aim to integrate their developmental effects and connect these to evolutionary outcomes at the population (“micro-”) and species (“macro-evolutionary”) level. We have generated genetic mapping resources to investigate the genetic architecture of adaptation in Faroese house mice—a population that exhibits island gigantism and other unique developmental traits, and is a complex hybrid between musculus and domesticus subspecies. Building on our previous work, we will directly compare how adaptation proceeds under natural and artificial selection.

Lineage-specific adaptations can arise through rewiring of gene regulatory networks and, in contrast to protein coding changes, may be particularly important in adaptation. We will test comparative genomic hypotheses of regulatory control by engineering mice to carry specific mutations, and evaluating their impact on long-range gene regulation, genomic organization and developmental phenotypes.

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.
(click to enlarge)
Left, many generations of artificial selection for either high or low bodyweight results in mice that differ significantly in size, similar to “island gigantism” phenotypes observed in the wild (note: apparent body length in wild mice is distorted due to skin preservation methods, which caused considerable stretching). Right, complex gene regulation networks control many polygenic traits, such as body weight in mice. A circular representation of the mouse genome shows how different parts of the genome contribute to body weight variation (inner circle, blue). This corresponds in many cases to accumulated parallel divergence between mice selected for increased body weight (outer plot, red). Comparison of gene expression shows that this may be due to the distributed effect of regulation of gene expression, or trans expression QTL effects (inner circle, curved links: those matching parallel selected regions in red, those lying far from parallel selected regions, yellow). Image credit: Frank Chan

(click to enlarge)
Molecular basis of adaptation via long-range enhancers. Developmental regulator genes like Pitx1 are often controlled by many regulatory elements (grey circles). We have identified the molecular mutations leading to pelvic reduction in several lake forms of sticklebacks. Detailed sequencing and genotyping revealed that multiple deletions remove a shared 484bp region (grey bars; flanking intact DNA represented as blue bars) that controls tissue-specific activation of Pitx1 transcription (red bars). We aim to extend such analysis to understand the developmental consequences of various mammalian adaptations by mouse genetic engineering. Image credit: Frank Chan