From human genetics to microbial pathogenesis, much of biology is concerned with how genes, environment and random chance combine to create differences between individuals. In the Siegal Lab, we use large-scale microscopy and DNA sequencing to study the genetics and evolution of complex traits. We focus most of our experiments on the model organism Saccharomyces cerevisiae (budding yeast), because it enables massive sample sizes for understanding cell-to-cell variation in quantitative detail.

Loss of HTZ1, a histone variant, causes otherwise genetically identical cells to have more diverse shapes and sizes, and also modifies the impacts of genetic differences on cell shape and size.

Genes that control the amount of variation in cellular traits

Genetically identical yeast cells, grown in the same benign environment, differ in their rates of growth, their gene expression (here TSL1-GFP), and their susceptibility to sudden heat stress.

Variability in growth and survival without genetic differences

Bulk-segregant analysis (BSA) powerfully identifies individual gene variants contributing to trait differences. Chromosome substitution enables BSA to identify genetic interactions.

Genetic basis of differences in complex traits

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