Research

The forces influencing evolutionary adaptations are undoubtedly governed by historic constraints: an organism’s past constrains its future. To what degree, however, do prior mutations and ancestral phenotypes shape future evolutionary pathways? Did life in the past function or evolve similarly to life today? Did the biology of ancestral organisms, the functions of their proteins or other factors inherently limit their ability to evolve into modern forms? To attempt to overcome these historical limitations we set up experimental systems by combining tools drawn from phylogenetics, synthetic biology, experimental evolution, whole-genome sequencing and biochemistry. The key questions that drive our research are:

  • How do proteins evolve their functions?
  • How do genes and genomes co-adapt?
  • How does an ancient component evolve within a modern host?
  • How does a lineage’s prior history shape its future evolutionary trajectories, and are there deterministic paths along these trajectories?
  • Are there evolutionary design principles that can be accessed by monitoring co-adaptation of an ancient protein and the modern genome?
  • Can we map the phenotype of an ancient component onto a modern genotype?

Our ability to reconstruct the historical steps of evolution is limited by our ability to directly and reliably access evolutionary history. Our current understanding of the historical record of evolution comes primarily from fossil and phylogenetic inferences, which often have considerable uncertainties. The fossil record provides insightful morphological evidence and benchmarked time points for large-scale, evolutionarily significant events, but its radical incompleteness and reliance upon extant organisms or microfossils as morphological interpretive guides limit its usefulness (Losos 2011Bapst 2013). Phylogeny provides another source for reconstructing evolutionary histories through inference (Felsenstein 1981Hedges 2009). Paleogenetics, or ancestral gene resurrection, is a phylogenetic method in which Bayesian inferences of extant sequence data permit reconstruction of putative ancestral gene and protein sequences (Benner 1995; Pauling 1965; Thornton 2004). Paleogenetic methods may be extended to test hypotheses related to the deep evolutionary past or to identify historically significant mutation sites for genes and proteins, providing insights into the mutational basis of evolutionary innovations (Harms 2013; Voordeckers 2012) and sequence and structural level protein evolution through billions of years of evolutionary time (Akanuma 2013; Gaucher 2008), and more (Wilson 2015). However, paleogenetics as it is currently practiced falls short of providing insights into how the inferred sequences functioned in the cellular environment(s) of the ancestral organisms themselves (Kacar 2013).

In its simplest form, our approach allows us to infer ancestral gene and protein sequences through phylogeny, followed by synthesis and evolution of these sequences in the laboratory and empirically testing hypotheses about how proteins evolved into their specific function. One of our primary goals is to identify how ancestral states of a protein affect cellular behavior by directly engineering an ancient gene inside a modern genome. We then identify the evolutionary steps of these ancient-modern hybrid organisms by subjecting them to laboratory evolution, and directly monitoring any resulting changes within the integrated ancient gene and the rest of the host genome.

We conduct our research activities under two themes:

  1. Molecular Mechanisms of Cellular Evolution
  2. Reconstructing Ancient Phenotypes

Feel free to email us for further information. We always welcome collaboration ideas!

Update: We are hiring, please see Opportunities