BackgroundWith the urgent need to reduce carbon emissions, and the dwindling reserves of easily exploitable fossil fuel, microalgae-based biofuels that can be used for transport systems and CO2abatement have attracted great attention worldwide in recent years. One useful characteristic of microalgae is their ability to accumulate high levels of lipid content, in particular under conditions of nitrogen deprivation, with numerous species identified so far. However, a trade-off between levels of lipid accumulation and biomass productivity hinders the commercial applicability of lipids from microalgae. Here, we sequenced the genomes ofVischeriasp. CAUP H4302 andVischeria stellataSAG 33.83, which can accumulate high content of lipids rich in nutraceutical fatty acids and with excellent biomass yield in nitrogen-limiting culture.ResultsA whole-genome duplication (WGD) event was revealed inV. sp. CAUP H4302, which is a rare event in unicellular microalgae. Comparative genomic analyses showed that a battery of genes encoding pivotal enzymes involved in fatty acids and triacylglycerol biosynthesis, storage polysaccharide hydrolysis, and nitrogen and amino acid-related metabolisms are expanded in the genusVischeriaor only inV. sp. CAUP H4302. The most highlighted is the expansion of cyanate lyase genes in the genusVischeria, which may enhance their detoxification ability against the toxic cyanate by decomposing cyanate to NH3and CO2, especially under nitrogen-limiting conditions, resulting in better growth performance and sustained accumulation of biomass under the aforementioned stress conditions.ConclusionsThis study presents a WGD event in microalgae, providing new insights into the genetic and regulatory mechanism underpinning hyper-accumulation of lipids and offering potentially valuable targets for future improvements in oleaginous microalgae by metabolic engineering.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12915-023-01618-x.