Friedrich Miescher Laboratory

  • Molecular basis and evolution of complex traits

“Nothing in biology makes sense except in the light of evolution” - Dobzhansky

We aim to track how species evolve by linking DNA basepairs to traits under selection.

Adaptation occurs all around us. Our DNA is the product of millions of years of evolution. Our group aims to connect genetic variation with its phenotypic and evolutionary impact. We want to understand how the genome encodes for robust development, and yet retains ample flexibility to respond rapidly to selection. To do so, we leverage uniquely informative systems like hybrid mice and selection experiments and apply (or invent!) cutting-edge genomic and stem cell techniques to chart the genetic circuitry of the genome as an dynamic system.

To track how selection operates in the genome, we sequence more than a thousand mice from the “Longshanks selection experiment” to make mice with longer legs. To map mouse species differences we developed in vitro recombination to circumvent the species barrier. To understand what makes Bloom Syndrome patient prone to cancer we used haplotagging to directly detect mitotic recombination events. By integrating these results, our goal is to understand how an organism works and evolves.

We aim to:

Retrace the steps of evolution by mapping and tracking genes and alleles important to selection. Can we uncover the rules and dynamics behind evolutionary change?

Sidestep barriers between species and directly recreate hybrid mosaic genomes in culture to better understand how gene networks produce organismal traits.

Capture what makes a single molecule, or a single cell, unique. Apply the power of genomics and molecular barcoding to reconstruct molecular events.

Integrate across molecular mechanisms and evolutionary outcomes. Can we find smart ways to quantify and distill data to reveal essential features from large datasets?

Natural selection is a mechanism for generating an exceedingly high degree of improbability.

R.A. Fisher

 

Key Publications

  1. 2021 Meier, J.I.*, Salazar, P.A.*, Kučka, M.*, Davies, R.W., Dréau, A., Aldás, I., Box-Power, O., Nadeau, N., Bridle, J.R., McMillan, W.O., Rolian, C.P., Jiggins, C.D.†, Chan, Y.F.† Haplotype tagging reveals parallel formation of hybrid races in two butterfly species. (* co-first authors; † co-last authors). PNAS, doi: 10.1073/pnas.2015005118.
  2. 2019 Castro, J.P.L.*, Yancoskie, M.N.*, Marchini, M., Belohlavy S., Hiramatsu, L., Kučka, M., Beluch, W.H., Naumann R., Barton, N.H., Rolian, C.†, Chan, Y.F†. An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. eLife, (8):e42014. doi: 10.7554/eLife.42014. * co-first authors; † co-last authors;
  3. 2018 Lazzarano, S., Kučka, M., Castro, J.P.L., Naumann, R., Medina, P., Fletcher, M.N-C., Wombacher, R., Gribnau, J., Hochepied, T., Van Montagu M., Libert C., Chan, Y.F. Genetic mapping of species differences via “in vitro crosses” in mouse embryonic stem cells. PNAS 115 (14) 3680-3685; Online Early. doi: 10.1073/pnas.1717474115.
  4. 2012 Chan, Y.F., Jones, F.C., McConnell, E., Bryk, J., Bünger, L., Tautz, D. 2012. Parallel selection mapping using artificially selected mice reveals bodyweight control loci. Current Biology. 22 (9): 794-800.
  5. 2010 Chan, Y.F., Marks, M.E., Jones, F.C., Villarreal G. Jr., Shapiro, M.D., Brady, S.D., Southwick, A.M., Absher, D.M., Grimwood, J., Schmutz, J., Myers, R.M., Petrov, D., Jónsson, B., Schluter, D., Bell, M.A., Kingsley D.MAdaptive evolution of pelvic reduction in sticklebacks by recurrent deletion of a Pitx1 enhancer. Science (Article) 327 (5963): 302-305.

see full publication list here

Watch

How genomes evolve? DSSS seminar 04.Jun.2021.