Most microbes have complex life cycles with multiple modes of reproduction that differ in their effects on DNA sequence variation. Population genomic analyses can therefore be used to estimate the relative frequencies of these different modes in nature. The life cycle of the wild yeast Saccharomyces paradoxus is complex, including clonal reproduction, outcrossing, and two different modes of inbreeding. To quantify these different aspects we analyzed DNA sequence variation in the third chromosome among 20 isolates from two populations. Measures of mutational and recombinational diversity were used to make two independent estimates of the population size. In an obligately sexual population these values should be approximately equal. Instead there is a discrepancy of about three orders of magnitude between our two estimates of population size, indicating that S. paradoxus goes through a sexual cycle approximately once in every 1,000 asexual generations. Chromosome III also contains the mating type locus (MAT), which is the most outbred part in the entire genome, and by comparing recombinational diversity as a function of distance from MAT we estimate the frequency of matings to be Ϸ94% from within the same tetrad, 5% with a clonemate after switching the mating type, and 1% outcrossed. Our study illustrates the utility of population genomic data in quantifying life cycles. mating systems ͉ inbreeding ͉ sex ͉ nucleotide polymorphism ͉ linkage disequilibrium M icrobial life cycles are often difficult to study because the organisms involved are so small. Laboratory studies can reveal what a species is capable of doing, but give little information on the frequencies of different modes of reproduction in nature. Instead, we must look at patterns of DNA sequence variation to infer the reproductive system. Pioneered by studies in bacteria, genealogical analyses have been very fruitful in uncovering sex where sexual stages had not been seen, and cryptic species where only one taxon had been recorded (1-4). Quantifying the different aspects of the life cycle, however, has been difficult. Population genomic data now allow accurate measures of mutational and recombinational diversity, and theory predicts that these parameters can be used to estimate the frequencies of different modes of reproduction in the life cycle, including frequencies of sex, outcrossing, and various forms of inbreeding.The bakers' yeast Saccharomyces cerevisiae has long been a model system in genetics and cell biology; more recently, together with its undomesticated relatives Saccharomyces paradoxus and Saccharomyces cariocanus, it is also becoming a focus of studies in ecology and evolution (5-7). Laboratory studies indicate that when conditions are good the primary mode of reproduction is vegetative budding of diploid cells. Starvation induces meiosis, each diploid cell producing a tetrad of haploid spores of two different mating types (a and ␣), enclosed within an ascus (8). When conditions improve, the spores germinate and are constitutively ready to...