Grain produced from cereal crops is a primary source of human food and animal feed worldwide. To understand the genetic basis of seed-size variation, a grain yield component, we conducted a genome-wide scan to detect evidence of selection in the maize Krug Yellow Dent long-term divergent seed-size selection experiment. Previous studies have documented significant phenotypic divergence between the populations. Allele frequency estimates for 3 million single nucleotide polymorphisms (SNPs) in the base population and selected populations were estimated from pooled whole-genome resequencing of 48 individuals per population. Using F ST values across sliding windows, 94 divergent regions with a median of six genes per region were identified. Additionally, 2729 SNPs that reached fixation in both selected populations with opposing fixed alleles were identified, many of which clustered in two regions of the genome. Copy-number variation was highly prevalent between the selected populations, with 532 total regions identified on the basis of read-depth variation and comparative genome hybridization. Regions important for seed weight in natural variation were identified in the maize nested association mapping population. However, the number of regions that overlapped with the long-term selection experiment did not exceed that expected by chance, possibly indicating unique sources of variation between the two populations. The results of this study provide insights into the genetic elements underlying seed-size variation in maize and could also have applications for other cereal crops.G RAIN produced by cereal crops is a staple food source in many regions of the world in terms of direct human consumption and as an animal feed source. Understanding the molecular mechanisms underlying cereal grain yield and exploiting that knowledge through improved cultivars is essential to providing a stable food source to an ever-growing human population. Yield-component traits are of particular interest, as they generally have a higher heritability than grain yield per se (Austin and Lee 1998). For example, increasing seed size has been hypothesized as one method for increasing grain yield in cereal crops (Odhiambo and Compton 1987;Kesavan et al. 2013), and positive correlations between seed size and grain yield have been shown in maize (Peng et al. 2011) as well as other cereals such as Sorghum bicolor (L.) Moench (Yang et al. 2010). Maize is a prime species with which to explore natural and artificial variation related to grain-yield and yield-component traits in the cereals, as it is the most widely grown cereal crop worldwide and has vast genetic resources for probing the genetic basis of seed traits. The maize seed is composed of the embryo and endosperm that develop from double fertilization, the aleurone, which is an epidermal layer that covers the endosperm, and the maternal pericarp tissue. The endosperm, the primary storage component of the seed in maize, consists primarily of starch, while the embryo is high in oil conte...