# Directed evolution for cell separation in natural isolates of budding yeast reveals selection to deactivate AMN1 and the Rim101 pathway in haploids and selection in favor of Hawthorne's deletion in diploids

## TL;DR

This study shows how natural yeast populations evolve to separate cells by deactivating specific genes and causing chromosome deletions.

## Contribution

The paper reveals novel roles for the Rim101 pathway and CCH1 in cell separation and quantifies the rate of Hawthorne's deletion.

## Key findings

- Haploid yeast populations show strong selection to deactivate AMN1 and the Rim101 pathway.
- Diploid populations frequently undergo Hawthorne's deletion due to mating type locus fusions.
- A nonsynonymous mutation in CCH1 was found in diploid populations without large deletions.

## Abstract

Natural isolates of the yeast Saccharomyces cerevisiae were evolved under a transfer protocol that selected for cell separation and against clumpy growth. Whole-genome sequencing of haploid populations revealed strong selection to deactivate AMN1, a known regulator of postmitotic cell separation, as well as multiple instances of loss-of-function mutations to genes of the Rim101 pathway, pointing to a previously unknown role of the Rim101 pathway in regulating cell separation. In diploid populations, we observed repeated large partial deletions of chromosome III caused by fusions of the mating type loci MAT and HMR (Hawthorne's deletion) or MAT and HML (Strathern's circle). We measured the spontaneous rate of Hawthorne's deletion and found that it is within an order of magnitude of previously measured rates of whole-chromosome aneuploidy. A diploid population in which neither large deletion was detected instead fixed a heterozygous nonsynonymous mutation to the calcium channel CCH1, also pointing to a novel role for this gene in relation to cell separation.