Domestication of many plants has correlated with dramatic increases in fruit size. In tomato, one quantitative trait locus (QTL), fw2.2, was responsible for a large step in this process. When transformed into large-fruited cultivars, a cosmid derived from the fw2.2 region of a small-fruited wild species reduced fruit size by the predicted amount and had the gene action expected for fw2.2. The cause of the QTL effect is a single gene, ORFX, that is expressed early in floral development, controls carpel cell number, and has a sequence suggesting structural similarity to the human oncogene c-H-ras p21. Alterations in fruit size, imparted by fw2.2 alleles, are most likely due to changes in regulation rather than in the sequence and structure of the encoded protein.In natural populations, most phenotypic variation is continuous and is effected by alleles at multiple loci. Although this quantitative variation fuels evolutionary change and has been exploited in the domestication and genetic improvement of plants and animals, the identification and isolation of the genes underlying this variation have been difficult.Conspicuous and important quantitative traits in plant agriculture are associated with domestication (1). Dramatic, relatively rapid evolution of fruit size has accompanied the domestication of virtually all fruit-bearing crop species (2). For example, the progenitor of the domesticated tomato (Lycopersicon esculentum) most likely had fruit less than 1 cm in diameter and only a few grams in weight (3). Such fruit was large enough to contain hundreds of seeds and yet small enough to be dispersed by small rodents or birds. In contrast, modern tomatoes can weigh as much as 1000 grams and can exceed 15 cm in diameter (Fig. 1A). Tomato fruit size is quantitatively controlled [for example, (4)]; however, the molecular basis of this transition has been unknown.Most of the loci involved in the evolution and domestication of tomato from small berries to large fruit have been genetically mapped (5, 6). One of these QTLs, fw2.2, changes fruit weight by up to 30% and appears to have been responsible for a key transition during domestication: All wild Lycopersicon species examined thus far contain small-fruit alleles at this locus, whereas modern cultivars have large-fruit alleles (7). By applying a map-based approach, we have cloned and sequenced a 19-kb segment of DNA containing this QTL and have identified the gene responsible for the QTL effect.Genetic complementation with fw2.2. A yeast artificial chromosome (YAC) containing fw2.2 was isolated (8) and used to screen a cDNA library (constructed from the small-fruited genotype, L. pennellii LA716). About 100 positive cDNA clones were identified that represent four unique transcripts (cDNA27, cDNA38, cDNA44, and cDNA70) that were derived from genes in the fw2.2 YAC contig. A high-resolution map was created of the four transcripts on 3472 F 2 individuals derived from a cross between two nearly isogenic lines (NILs) differing for alleles at fw2.2 ( Fig. 2A) (8). The fo...