Offspring number and size are key traits determining an individual's fitness and a crop's yield. Yet, extensive natural variation within species is observed for these traits. Such variation is typically explained by trade-offs between fecundity and quality, for which an optimal solution is environmentally dependent. Understanding the genetic basis of seed size and number, as well as any possible genetic constraints preventing the maximization of both, is crucial from both an evolutionary and applied perspective. We investigated the genetic basis of natural variation in seed size and number using a set of Arabidopsis thaliana multiparent advanced generation intercross (MAGIC) lines. We also tested whether life history affects seed size, number, and their trade-off. We found that both seed size and seed number are affected by a large number of mostly nonoverlapping QTL, suggesting that seed size and seed number can evolve independently. The allele that increases seed size at most identified QTL is from the same natural accession, indicating past occurrence of directional selection for seed size. Although a significant trade-off between seed size and number is observed, its expression depends on life-history characteristics, and generally explains little variance. We conclude that the trade-off between seed size and number might have a minor role in explaining the maintenance of variation in seed size and number, and that seed size could be a valid target for selection.T HE reproductive output of an organism is a critical lifehistory trait defining its fitness and is the result of both offspring number and quality. In the case of cereal crops, the number and size of seeds are also the main constituents of yield. Thus, understanding the genetic architecture of seed size and number, and any possible genetic constraints to maximizing them, is crucial from both an evolutionary and applied perspective (Sadras 2007;Van Daele et al. 2012;Kesavan et al. 2013). Despite its importance, the genetic basis of natural variation in seed size and number and their interaction with life-history traits remain poorly understood.Previous studies on the genetic basis of seed traits have predominantly used mutant screens and identified genes in key pathways involved in seed development (Garcia et al. 2003;Tzafrir et al. 2004;Adamski et al. 2009;Fang et al. 2012). However, since this approach only allows for the comparison of phenotypic effects of genes that are "on" or "off" (Koornneef et al. 2004), genes' contribution to natural continuous variation in seed size or seed number remain largely uncharacterized. Because the effects of mutants are often dependent on the genetic background (Tonsor et al. 2005;Chou et al. 2011), a QTL mapping approach using multiple parents is ideal to identify genetic factors that can contribute to natural variation in these traits in a heterogeneous genetic background.Identification of genetic factors affecting seed traits is further complicated by potential trade-offs between them. Life-history the...