Extant species have wildly different chromosome numbers, even among taxa with relatively similar genome size. This raises the interesting question: how well can a species tolerate a change in “n” without significant changes to genome content? In this project we have successfully fused yeast chromosomes using CRISPR-Cas9, generating a near-isogenic series of strains with progressively fewer chromosomes ranging from n=16 to n=2. A strain carrying only two ~6 Mb long chromosomes exhibited only modest transcriptomic changes and strikingly, grows without major defects compared to the n=16 strain. Datasets for WGS and RNA-seq for selected strains with various values of n are provided.