Across the tree of life, genome size varies by over 6 orders of magnitude. Across this huge range, genome size consistently scales with nuclear size and cell size. An extreme form of genome size increase is called polyploidy, where entire copies of the genome are duplicated. Across many clades including plants, insects and amphibians, polyploidy correlates with innovation of new traits and bursts of speciation. Polyploidy can also occur within a single species, including humans. For example, polyploid cells in our liver, placenta and immune system have specialized functions that are critical for the health of the tissue. Polyploidy can also be drivers of disease–whole genome duplications are highly prevalent in the most untreatable forms of cancers. Our lab is interested in the fundamental question: how do genomes adapt to huge changes in size?
|
|
We take advantage of the naturally polyploid African clawed frog Xenopus. Xenopus species naturally vary 6-fold in ploidy, and we can artificially manipulate the ploidy of a single species. Xenopus are famous for their ability to lay thousands of giant eggs overnight. We use these eggs in the lab to generate embryos as well as cytoplasmic extracts that recapitulate events of early embryogenesis. Video credit: Xenbase
Our goal is to combine biochemistry, quantitative imaging, embryology and genomics to discover new molecular mechanisms that sense and adapt to changes in genome size that occur during embryogenesis and evolution. We envision that our discoveries will provide critical insights for how genomes naturally evolve and will empower new directions for treating diseases such as cancer.
Some questions we are currently excited about:
- Why do mitotic chromosomes shrink during early embryogenesis?
- How are silenced regions of the genome, called heterochromatin, established and maintained in the early embryo? How are these regions dynamically organized within a 3D nucleus as genome size increases?
- How are huge genomes packaged into chromatin?
- How are huge genomes replicated and repaired?