Selection of highly productive algal strains is crucial for establishing economically viable biomass and bioproduct cultivation systems. Characterization of algal genomes, including understanding strain-specific differences in genome content and architecture is a critical step in this process. Using genomic analyses, we demonstrate significant differences between three strains of Chlorella sorokiniana (strain 1228, UTEX 1230, and DOE1412). We found that unique, strain-specific genes comprise a substantial proportion of each genome, and genomic regions with >
80% local nucleotide identity constitute <
15% of each genome among the strains, indicating substantial strain specific evolution. Furthermore, cataloging of meiosis and other sex-related genes in C. sorokiniana strains suggests strategic breeding could be utilized to improve biomass and bioproduct yields if a sexual cycle can be characterized. Finally, preliminary investigation of epigenetic machinery suggests the presence of potentially unique transcriptional regulation in each strain. Our data demonstrate that these three C. sorokiniana strains represent significantly different genomic content. Based on these findings, we propose individualized assessment of each strain for potential performance in cultivation systems.