Fruit Development and Ripening

PP64CH10-Seymour ARI 23 March 2013 14:57

Graham B. Seymour,1 Lars Østergaard,2 Natalie H. Chapman,1 Sandra Knapp,4 and Cathie Martin3

1Plant and Crop Science Division, School of Biosciences, University of Nottingham, Loughborough LE12 5RD, United Kingdom; email: [email protected], [email protected] 2Department of Crop Genetics and 3Department of Metabolic Biology, John Innes Center, Norwich NR4 7UH, United Kingdom; email: [email protected], [email protected] 4Department of Life Sciences, Natural History Museum, London SW7 5BD, United Kingdom; email: [email protected]

Annu. Rev. Plant Biol. 2013. 64:219–41 Keywords First published online as a Review in Advance on Arabidopsis, tomato, diet, gene regulation, epigenetics February 4, 2013 The Annual Review of Plant Biology is online at Abstract plant.annualreviews.org Fruiting structures in the angiosperms range from completely dry to This article’s doi: highly ﬂeshy organs and provide many of our major crop products, by Universidad Veracruzana on 01/08/14. For personal use only. 10.1146/annurev-arplant-050312-120057 including grains. In the model plant Arabidopsis, which has dry fruits, Copyright c 2013 by Annual Reviews. a high-level regulatory network of transcription factors controlling All rights reserved

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org fruit development has been revealed. Studies on rare nonripening mutations in tomato, a model for fleshy fruits, have provided new insights into the networks responsible for the control of ripening. It is apparent that there are strong similarities between dry and fleshy fruits in the molecular circuits governing development and maturation. Translation of information from tomato to other fleshy-fruited species indicates that regulatory networks are conserved across a wide spectrum of angiosperm fruit morphologies. Fruits are an essential part of the human diet, and recent developments in the sequencing of angiosperm genomes have provided the foundation for a step change in crop improvement through the understanding and harnessing of genome-wide genetic and epigenetic variation.

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in land plants other than angiosperms; some Contents Carboniferous seed ferns had fleshy structures that are thought to have been eaten by reptiles INTRODUCTION...... 220 (148), and the seed of the “living fossil” Ginkgo NOMENCLATURE, EVOLUTION, biloba is enveloped in a soft fleshy covering DIVERSITY...... 220 called the sarcotesta. These propagules are not FRUIT DEVELOPMENT AND considered true fruits despite their functional RIPENING...... 222 similarities. True fruits are derived from the TheFruitingStructure...... 222 flower gynoecium (see Fruit Development and Hormonal and Genetic Ripening, below). Regulation...... 223 Fertilization...... 224 Fruit Development...... 225 NOMENCLATURE, EVOLUTION, Hormonal and Genetic Regulation DIVERSITY of Maturation and Dehiscence The myriad of fruit types recognized in an- inDryFruits...... 227 giosperms can be simplified using combinations Hormonal and Genetic Regulation of the following characteristics: dehiscence or of Maturation and Ripening indehiscence, dry or fleshy exterior, and free inFleshyFruits...... 228 (apocarpous) or fused (syncarpous) carpels. FRUITS AND THE HUMAN Capsules (Figure 1c) and the siliques of DIET...... 232 Arabidopsis relatives (Figure 1a) are dehis- CROP IMPROVEMENT ...... 233 cent, dry, and syncarpous; achenes and nuts (Figure 1e,g,h) are indehiscent, dry, and unicarpellate; and berries (Figure 1b,d)are indehiscent, fleshy, and syncarpous. A drupe INTRODUCTION is an indehiscent, fleshy, single-seeded fruit True fruits are found only in the angiosperms, where the seed is enclosed in a hard endocarp, or flowering plants; the name angiosperm like a peach pit (Figure 1f ). Syncarpy occurs Gynoecium: the carpels or female means hidden seed. Flowering plants comprise in 83% of extant angiosperm species and has reproductive organs of some 250,000–400,000 species in four major been interpreted as facilitating pollen tube flowering plants, clades (10) that are the dominant component competition and thus fitness (36); it has arisen consisting of an ovary of vegetation in most tropical, subtropical, and independently in both the monocots and the harboring the ovules, temperate zones worldwide. The angiosperms eudicots (37). Apocarpy is rarer but can be by Universidad Veracruzana on 01/08/14. For personal use only. stigmatic tissue for pollen reception at the comprise tiny herbs to large canopy trees, oc- seen in the fruits of magnolias, with clusters of top, and a gynophore cupy terrestrial and aquatic (including marine) separate carpels termed follicles. Endress (36)

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org at the base connecting habitats, and are the source of all major crop has suggested that syncarpy might facilitate the gynoecium to the plants. As such, humans have a long and inti- adaptive radiation in fruit type by increasing plant mate association with angiosperms, particularly the possibility of developing fleshiness and/or Apocarpous: having with their fruits and seeds. dehiscence mechanisms. free carpels Fruits are often defined as structures derived Darwin thought that the recent origin and Syncarpous: having from a mature ovary containing seeds (48), but rapid diversification of the angiosperms was fused carpels many structures we might define as fruit are “an abominable mystery” (44). The angiosperm Nut: indehiscent fruit in fact composed of a variety of tissue types fossil record extends back to the Early Cre- with a hard shell (Figure 1). Van der Pijl (155) used the concept taceous period, and the earliest unambiguous Berry: fleshy fruit of the dispersal unit as his definition of a fruit; fossils (65) are dated conservatively to approx- produced from a single this links fruits to their role in the ecology of imately 132 Mya. Angiosperms were common ovary, often with many seeds the plant life cycle as the mechanism by which and diverse by the mid-Cretaceous, indicating seeds are dispersed. Dispersal units also occur either that their first major diversification and

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Figure 1

by Universidad Veracruzana on 01/08/14. For personal use only. Fruit diversity. (a) Lunaria annua L. (Brassicaceae), cultivated, United Kingdom: dehiscent siliques that dry and shatter irregularly with age, releasing the seeds. (b) Mandragora ofﬁcinalis L. (Solanaceae), Andalucıa,´ Spain: indehiscent berries with ﬂeshy, brightly colored mesocarp and many seeds. (c) Nicotiana sylvestris

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org Speg. & Comes (Solanaceae), Apurımac,´ Peru: dehiscent capsules opening along suture lines. The seed-bearing placentae are visible as columns in the center of the capsule. (d ) Ribes cereum Douglas (Grossulariaceae), New Mexico, United States: indehiscent berries from an inferior gynoecium. The remnants of the flower are clearly visible. (e) Corylus sp. (Betulaceae), cultivated, United Kingdom: indehiscent, single-seeded nuts. ( f ) Rhus trilobata Nutt. (Anacardiaceae), New Mexico, United States: indehiscent, single-seeded drupes with fleshy mesocarp. ( g) Fallugia paradoxa (D. Don) Endl. (Rosaceae), New Mexico, United States: indehiscent, single-seeded achenes with long plumes to aid dispersal. Drupe: indehiscent × (h) Fragaria ananassa Duchesne ex Rozier (Rosaceae), cultivated, United Kingdom: tiny, single-seeded fruit with fleshy outer achenes on the surface of an expanded, brightly colored receptacle. All photos by Sandra Knapp. pericarp layers (exocarp and ecological radiation occurred over a relatively taceous angiosperms were mostly very small mesocarp) but a hard short time frame or that they originated and (45), with fruit volumes between 0.1 and inner pericarp layer diversified earlier than was previously thought. 8.3 mm3 (the size of a small cherry) and seed vol- (endocarp) surrounding the seed The reproductive structures of these Early Cre- umes between 0.02 and 6.9 mm3 (39). Diverse

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fruit types are represented in Early Cretaceous It is tempting to assume that fruit diversity fossils; the vast majority are either indehiscent, is the result of adaptation to frugivores; adapta- single-seeded nuts or drupes with one or a few tionist scenarios about tight obligate relation- seeds, but some dehiscent, apocarpous fruits ships between fruits and their dispersers abound have been found, as have many fruits with fleshy in the literature, but they have been shown to outer layers (45). One-quarter of all fruits found be less compelling than originally thought. The at one site were fleshy drupes or berries (40). strong role of habitat and climate in the ori- Lorts et al. (91) mapped crude fruit type gin and evolution of fruit characteristics such categories (dry dehiscent, dry indehiscent, and as fleshiness (39) has been clearly demonstrated fleshy) onto the orders of extant angiosperms in both the fossil record and through correla- and found no association (assessed visually) be- tion studies with extant angiosperms. Syncarpy tween fruit type and major clade. This suggests may represent a key innovation for angiosperm that there is no phylogenetic constraint on fruits in that it facilitated pollen competition fruit type evolution across the major lineages and pollen tube protection (37). Fruit color is (orders) of angiosperms, with most orders another characteristic that on its face seems to having all three broadly defined fruit types be adaptive for frugivore attraction, but studies (see figure 1 of Reference 91). Fruit and seed examining color as a signal have demonstrated size both increased in the Tertiary (39), with that, like the evolution of other fruit character- a drastic change at the Cretaceous–Tertiary istics, the evolution of fruit color is mediated boundary (147, 162). It has been suggested through diffuse interactions between plants, an- that the origin of fleshiness was initially related tagonists (such as microbial predators), and mu- to defense against pathogens and only later tualists (128). Fleshy-fruit evolution has clearly co-opted for biotic dispersal (93, 149). been an important and continually recurring Size change in both fruits and seeds through theme throughout flowering plant evolution, the fossil record has been attributed to co- and assumptions with respect to the adaptive evolution with seed-dispersing animals (147), value of particular fruit traits must be carefully with this mutualistic relationship then driving examined. the development of closed, forested habitats (large seeds are characteristic of closed plant communities). An alternative hypothesis is that FRUIT DEVELOPMENT AND changes in habitat through climate change, per- RIPENING haps coupled with the demise of large herbi- The Fruiting Structure vores (e.g., dinosaurs), drove the evolution of by Universidad Veracruzana on 01/08/14. For personal use only. larger fruits and seeds, and the availability of The gynoecium is derived from the fusion of seed dispersers reinforced this trend (39). Dis- carpels and forms in the center of the flower.

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org persers thus tracked, rather than led, changes Many regulators of carpel development identi- in fruit size and morphology. Distinguishing fied in Arabidopsis also have roles during leaf de- between these two hypotheses is difficult ow- velopment, thereby confirming the evolution- ing to bias in the fossil record (39) and un- ary origin of carpels as modified leaves (41, 129). certainty over ecological dynamics in the past The main patterning events of the Arabidopsis (149), but a series of studies using both ex- gynoecium take place before fertilization and tant and fossil fruits have strongly supported occur along three axes: apical-basal, mediolat- the latter hypothesis. The significant correla- eral, and abaxial-adaxial (dorsoventral). Stig- tions between fruit type and habitat conditions matic tissue (Figure 2) that mediates pollen in a broad set of extant flowering plants (8) sug- germination develops at the apical (distal) end. gest that the evolution of fleshiness is related After germination, the pollen tube grows down to changes in vegetation from open to closed through the transmitting tract and enters the habitats. ovules through the micropyle, a small opening

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in the integument layers (90). A solid style with a b d radial symmetry supports the segment of the transmitting tract just below the stigma and is SStiStStigmatiggmama required for efficient fertilization (Figure 2). StyleStySSttytylee The ovary is formed from the carpels as a lon- gitudinal cylinder with mediolateral symmetry ValveValve 50 µm Transmitting that reflects its origin as two fused leaflike or- ValveValve tract gans (Figure 2). It is composed of two com- marginmargin Septum partments divided by a septum and placenta ReplumReplum c from which ovules arise. The carpel walls exhibit abaxial-adaxial asymmetry with an exocarp layer of large cells interspersed with stomata, three or four layers of mesocarp cells, and two 50 µm Ovule innermost layers of endocarp cell layers. The GynophoreGynophore Arabidopsis gynoecium is connected at its base 220000 µµmm 200 µm to the pedicel and the rest of the plant via a gynophore. Figure 2 Arabidopsis gynoecium patterning. (a) False-colored scanning electron micrograph (SEM) of a stage-13 gynoecium, showing the stigma ( yellow), style Hormonal and Genetic Regulation (blue), valves ( green), replum (red ), valve margins (turquoise), and gynophore The plant hormone auxin has been estab- ( purple). (b) Cross section of a radial symmetric style with a transmitting tract (orange). (c) Cross section of an ovary with bilateral symmetry. Color lished as an important component for pat- coding is identical to that in panels a and b, with the addition of the septum terning along the different axes of polarity (dark blue) and ovules ( gray). (d ) False-colored SEM of an ind spt in the Arabidopsis gynoecium. In the apical- double-mutant stage-13 gynoecium that completely lacks the stigmatic tissue basal orientation, auxin synthesis at the apex and radial style. The surface of the cells at the very apical part of the valves is required for specification of the style and suggests that they have retained style identity. stigma (137). Auxin biosynthesis at the apex is promoted through the activity of transcrip- observed in spt mutant gynoecia were observed tion factors such as STYLISH1 (STY1), STY2, in multiple combinations of mutations in the and NGATHA3, which induce expression of bHLH-encoding HECATE (HEC) genes, and YUCCA auxin biosynthesis genes (2, 15, 34, protein-protein interactions between SPT and 137, 153). Exogenous application of auxin res- HEC proteins in yeast two-hybrid experiments cues the split style of the sty1/2 mutant (141). suggest that these factors may jointly regulate by Universidad Veracruzana on 01/08/14. For personal use only. The basic helix-loop-helix (bHLH) pro- downstream targets (55). Loss-of-function teins are a large family of transcription factors mutations in the ETTIN (ETT ) gene, which

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org found in all eukaryotic organisms (99, 115). encodes AUXIN RESPONSE FACTOR3 Several members of this family have functions (ARF3), exhibit enlarged apical and basal during gynoecium development or later in regions at the expense of the ovary (132). fruit development. For example, mutations Because ETT negatively regulates SPT/HEC in the SPATULA (SPT ) gene lead to early genes in the ovary, it has been suggested that defects in the development of carpel marginal ETT regulates ovary size, perhaps in response tissues such as the stigma, style, septum, and to local auxin dynamics (61, 108, 144). transmitting tract (3, 61). SPT activity promot- Further connections between gynoecium ing carpel development was recruited during patterning and auxin were made when it the evolution of ﬂowering plants from light- appeared that mutations in another bHLH- regulated processes such as those involved in factor-encoding gene, INDEHISCENT (IND), shade-avoidance responses in vegetative organs strongly enhanced the phenotype of the spt (120). Phenotypic defects similar to those single mutant (51) (Figure 2d ). IND and SPT

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heterodimerize in plant cells and regulate a DELLAs are characterized by a conserved common set of target genes (51, 139), and a DELLA motif in the N-terminal domain and a number of their direct targets are involved in SCARECROW-like C-terminal domain (113, Parthenocarpic: producing fruit controlling the direction of auxin transport 136). According to the “relief of restraint” without fertilization; (51, 139). IND belongs to the same clade model (58), GA-mediated DELLA degradation the resulting fruits are in the Arabidopsis bHLH family as the three is required to overcome the growth-repressing seedless HEC genes (115). Loss of all three HEC genes DELLA activity. In agreement with their gives rise to a split-style phenotype with no function as growth repressors, reduction in stigmatic tissue, identical to the ind spt mutant DELLA activity can promote parthenocarpic gynoecium (55), and it is therefore likely that fruit growth in both dry dehiscent fruits HEC proteins also interact with SPT in planta. and fleshy fruits (32, 97). GA treatment of Tissue identity factor activity and auxin dy- gynoecia in a della loss-of-function mutant namics are at the center of gynoecium pat- has revealed the existence of a GA-dependent terning control. With the development of tools but DELLA-independent pathway that con- to study auxin transport and signaling in Ara- tributes to fruit growth in Arabidopsis (46). bidopsis, data are now emerging to provide an This newly identified DELLA-independent overview of how auxin is distributed during gy- pathway provides additional opportunities for noecium development. For example, the auxin fine-tuning fruit growth. signaling reporter DR5::GFP shows a strong ARFs and Aux/IAA proteins also function green fluorescent protein (GFP) signal accu- during fruit initiation. In Arabidopsis and mulating in a ring at the distal end of the tomato, expression of aberrant forms of ARF8 gynoecium prior to stigma formation (51). In results in parthenocarpic fruit development the spt single mutant and the ind spt double (53, 54), as does silencing of IAA9 in tomato mutant, this ring is not formed; instead, the (160). It is not clear by what mechanism ARF8 GFP signal accumulates in two foci at the dis- regulation occurs, but based on the model for tal end. Because both IND and SPT are ex- auxin signal transduction, it has been suggested pressed in this distal region, it is likely that they that ARF8 and the Aux/IAA protein IAA9 may are responsible for lateral auxin distribution form a transcriptional repressor complex that is to create a continuous ring and ensure proper destabilized by the aberrant forms of ARF8 to development. allow transcription of auxin-responsive genes (53). In tomato, pollination causes upregulation Fertilization of ARF9 and downregulation of ARF7. Silenc- by Universidad Veracruzana on 01/08/14. For personal use only. The developmental switch that turns a gynoe- ing of the SlARF7 gene in transgenic plants cium into a growing fruit depends on the fertil- (cv. Moneymaker) results in parthenocarpic

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org ization of ovules that form along the placenta. In fruit development, suggesting that SlARF7 most angiosperms, the gynoecium senesces and is a negative regulator of fruit set. Silencing dies if not fertilized. The fruit initiation proof SlARF7 also results in strong upregulation cess has traditionally been thought to involve of SlGH3, which encodes an IAA–amido phytohormone activities (49). Upon fertiliza- synthetase that may be induced to compensate tion, a seed-originating auxin signal is gener- for excessive auxin (25, 26). Differences in cell ated (32, 104, 126) that is thought to upregulate size between SlARF7-silenced lines and the biosynthesis of another hormone, gibberellin wild type become apparent 6 days postanthesis (GA). This leads to activation of GA signaling in (DPA), with signiﬁcant cell size increase in the the ovules and valves, thereby stimulating fruit mesocarp and endocarp layers, and so it has growth (32, 111, 131, 156). been concluded that downregulation of SlARF7 Degradation of the growth-repressing deregulates cell division and upregulates cell DELLA proteins is central to GA signaling. expansion (26). In addition, there is evidence in

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tomato that early photosynthesis is important tissues, but without the lignification phase for proper seed set (92). found in dry fruit. In the miniature tomato (cv. Micro-Tom) (112), cell division starts at 2 Quantitative trait DPA, when the ovary is 1 mm in diameter with Fruit Development loci: DNA regions 10 cell layers (Figure 3). Cell divisions are both associated with a Upon fertilization, Arabidopsis fruit enters a periclinal and anticlinal, and by 4 DPA the fruit phenotype that is stage in which ovary growth and maturation is 1.5 mm in diameter and has 30 cell layers. controlled by two or are tightly coordinated with seed develop- Cell division continues at 7–8 DPA, but then more genes ment. During this process, a number of fruit cell expansion becomes apparent and the cell MADS-box genes: tissues develop, including valves (derived from layer number increases to 35 at the apex of the transcription factors detected in nearly all the carpel walls), a central replum, a false fruit and 20 at the equator. Cell division stops eukaryotes; in plants, septum, and valve margins that form at the by 10–13 DPA, and cell expansion progresses they are commonly valve/replum borders. Late in development, at a dramatic rate until approximately 30 DPA, associated with floral the valve margins differentiate into dehiscence when the fruit reaches a diameter of 1.5–2 cm development zones, where fruit opening will take place. (Figure 3). The layers of cells that undergo Although these individual tissues were specified division after anthesis are the mesocarp col- prior to fertilization, their distinct appearance lenchyma. Cell expansion is responsible for becomes more striking after fertilization, the increase in fleshy-fruit size (Figure 3), forming sharp boundaries, particularly along with cell sizes in tomato reaching 0.5 mm in the valve margin (125). diameter in the pericarps of some varieties (16). As described above, the valves (carpel walls) Fruit size in tomato is controlled by nearly exhibit abaxial-adaxial asymmetry and are com- 30 quantitative trait loci. The Fw2.2 gene posed of an outermost (abaxial) epidermal layer is responsible for approximately 30% of the with long, broad cells interspersed with guard variation, and encodes a plant-specific and cells (stomata). Underneath the epidermal fruit-specific protein that negatively regulates layer, three to six layers of mesophyll cells fol- mitosis and is possibly part of the cell cycle low (Figure 3). Two specialized adaxial cell lay- signal transduction pathway (20). Pericarp ers form in the valves: The innermost endocarp cell number in tomato is also linked to the A layer (valve margins) is composed of large expression of the MADS-box gene TOMATO cells that undergo cell death before the fruit has AGAMOUS (TAG)–LIKE1 (TAGL1), which completely matured, whereas cells in the endo- is an ortholog of the Arabidopsis SHATTER- carp B layer remain small and develop lignified PROOF (SHP) genes (158). TAGL1 is expressed cell walls (Figure 3) whose rigidity may assist in floral organs and young tomato fruit as well as by Universidad Veracruzana on 01/08/14. For personal use only. in the process of fruit opening by providing sig- during ripening. It is one of the most abundant nificant tension in the mature fruit (140). The MADS-box genes expressed in tissues of young

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org replum is connected to the septum and contains fruits (100), and in RNAi::TAGL1 tomato fruits the main vascular bundles. At the valve margin, there is a reduction in pericarp thickness from a narrow file of dehiscence zone cells differen- 25 to 15 layers measured at 28 and 38 DPA, re- tiates along the entire length of the fruit late spectively, and the inner pericarp appears to be in development, allowing the valves to detach absent. from the replum, which causes seed dispersal Four genes that control shape in tomato to occur by a shattering mechanism. The valve have been cloned: SUN and OVATE, which margins consist of two distinct cell layers: a sep- control fruit elongation shape; FASCIATED, aration layer, where cell separation will take which is associated with flat-shaped fruit; and place, and a layer of lignified cells, whose rigid- LOCULE NUMBER, which regulates fruit ity may promote the opening process (140). locule number. SUN encodes an IQD family Development of fleshy fruit such as tomato protein that is thought to alter hormone or involves cell division and expansion of the ovary secondary metabolite levels (164), whereas

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ab Exocarp Exocarp

Mesocarp Mesocarp

Endocarp

Exocarp

Mesocarp

Endocarp

200 µm 500 µm e 2 DPA 4 DPA 8 DPA 24 DPA

Exocarp

Mesocarp

50 µm 50 µm by Universidad Veracruzana on 01/08/14. For personal use only. 240 µm Endocarp

200 µm Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org Figure 3 Changes in fruit anatomy during development. (a) Pericarp layers characteristic of dry fruits (e.g., capsules). (b) Pericarp layers characteristic of ﬂeshy fruits. (c) Transverse section of entire mature Brassica pod. (d ) Transverse section of Brassica pod valve wall. (e) Transverse section of Solanum lycopersicum cv. Micro-Tom fruit at different days postanthesis (DPA), showing pericarp layers and illustrating cell division and cell expansion phases. Panels a, b,ande courtesy of Pabon-Mora´ & Litt (112).

OVATE encodes a negative growth regulator, linked to two single-nucleotide polymor- presumably by acting as a repressor of tran- phisms (SNPs) located approximately 1,200 scription and thereby reducing fruit length. base pairs downstream of the stop codon of a FASCIATED encodes a YABBY transcription gene encoding a WUSCHEL homeodomain factor (19). LOCULE NUMBER was recently protein, members of which regulate plant stem

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cell fate. Alleles of these genes appear to have in the replum, and combining rpl mutants with, played a critical role in forging the shape of for example, the shp double or ind single mutant domesticated tomato fruits (123). rescues the replum defect (122, 124). Species of Brassica produce fruits that are morphologically very similar to those of Arabidopsis, but they lack Hormonal and Genetic Regulation an outer replum, suggesting that brassicas have of Maturation and Dehiscence lost the RPL function in the fruit. Replum tis- in Dry Fruits sue was, however, produced in Brassica rapa with Formation of the valve margin region depends a strong ind mutant allele (52). Lack of RPL on several transcription factor activities. activity in Brassica fruits was demonstrated to Upstream in the hierarchy, two closely related result from reduced RPL gene expression due MADS-box transcription factor–encoding to a SNP in a cis-element located ∼3 kb up- genes, SHP1 and SHP2, positively regulate stream from the RPL-encoding region (5). In the IND gene described above as well as rice, the same SNP in the same cis-element in ALCATRAZ (ALC), which encodes another an RPL homolog is responsible for preventing bHLH transcription factor (83, 84, 118). seed shattering in domesticated rice (76), re- Although none of the shp single mutants have vealing a remarkable example in which the same any detectable phenotype on their own, the nucleotide position in a regulatory element ex- combined shp1 shp2 double mutant produces plains developmental variation in seed dispersal indehiscent fruit devoid of valve margin structures in widely diverged species (5). differentiation (83). Despite the role of IND in In recent years more elements of the core gynoecium formation, the most pronounced genetic network of Arabidopsis fruit patterning phenotypic defect of ind mutants and loss of have been identified, including genes involved IND function is a loss of valve margin identity in leaf development, such as ASYMMET- that affects both the lignified and separation RIC LEAVES1, ASYMMETRIC LEAVES2,and layers (84). In contrast, fruits from alc mutants BREVIPEDICELLUS (1). The network has also produce lignified cells at the valve margin, but expanded upstream to include a combination the separation layer cells fail to develop (118). of genes, including JAGGED, NUBBIN, FILA- The FRUITFULL (FUL) gene encodes a MENTOUS FLOWER,andYABBY3 (29, 30). MADS-box transcription factor that is required The floral homeotic gene APETALA2 (AP2) for maintaining valve identity (57). The valves has been demonstrated to repress replum de- developed in ful mutant fruits adopt a partial velopment (122). A thorough description of all change of identity into valve margin cells with these interactions is not the purpose of this re- by Universidad Veracruzana on 01/08/14. For personal use only. ectopic lignification. In these mutant valves, view and can be obtained at least partly else- SHP1, SHP2,andIND become ectopically ex- where (6, 110, 125). Therefore, here we con-

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org pressed, and the phenotype can be almost en- centrate on the core network and its interaction tirely rescued by combining the ful mutant with with hormonal activities. mutations in valve margin identity genes. FUL The core and extended genetic network of thus speciﬁes valve cell fate at least in part by re- Arabidopsis fruit development consists entirely pressing the expression of valve margin identity of interactions among transcription factors. genes in valve tissue (42, 84). The three genes encoding polygalacturonases The homeodomain-containing transcrip- (PGs) required for dehiscence downstream of tion factor REPLUMLESS (RPL) is a key reg- IND are functionally redundant (109). This ulator of the replum tissue on the medial side makes sense, as PGs have cell wall–degrading of the valve margins. As the name implies, rpl activities and secretion of PGs from dehiscence loss-of-function mutants fail to develop a re- zone cells has been demonstrated (114). plum. Similar to the activity of FUL, RPL re- Hormonal distribution and biosynthesis are presses valve margin identity gene expression emerging as immediate downstream outputs

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from the core genetic network. In Brassica na- IAA by IAA–amido synthetase, and this enzyme pus, direct measurements of auxin levels in valve is encoded by the GH3 gene. Two GH3 genes margin tissue revealed an abrupt decrease in the associated with the onset of ripening in tomato auxin content of these cells immediately prior to are upregulated (77), and tomato fruits over- fruit opening. This drop correlated exactly with expressing the pepper GH3 gene ripen early an increase in the activity of cell wall–degrading (88). These observations are consistent with enzymes (14), raising the possibility that auxin a role for endogenous IAA in controlling the depletion from the valve margin tissue is a re- onset of ripening and modulation of its levels quirement for dehiscence. Work in Arabidopsis by amino acid conjugation (9). GH3 expression confirmed this hypothesis, demonstrating that may be partially under the control of abscisic IND ensures formation of an auxin minimum in acid (ABA), another plant hormone that pro- the valve margins at maturity by regulating the motes ripening (9). direction of auxin transport (139); a subsequent There is evidence that ABA acts as a study showed that IND most likely interacts promoter of ripening in tomato. Suppres- with SPT to mediate this process (51). sion of the SlNCED1 gene (encoding 9-cis- As described earlier, GA promotes fruit epoxycarotenoid dioxygenase), which catalyzes growth in Arabidopsis following fertilization. a key step in ABA biosynthesis, results in down- This is in line with the general perception of GA regulation in the transcription of several major as a growth-promoting hormone, which func- ripening-related cell wall enzymes, including tions by promoting degradation of the growth- PG and pectin methylesterase; enhanced fruit repressing DELLA proteins (58). GA has now shelf life; and slower softening (143). Retarda- also been identified as having a role in tissue tion of ripening is also apparent in strawberry specification during Arabidopsis fruit develop- fruits with reduced levels of NCED (71). ABA is ment. The GA4 gene is a direct target of IND, also a positive regulator of ripening in grape (9). and the ga4 mutant has a defect in specifying The mechanism of ABA action is not known, the separation layer of the valve margin similar but in grape it can increase GH3 expression, to that seen in alc mutants (4). GA4 encodes a and a promoter scan identified ABRE-like ele- GA3 oxidase, which mediates the last step in the ments potentially involved in ABA signaling in biosynthesis of active GAs (17, 145). Genetic the GH3 promoter (9). analysis demonstrated that GA production at The role of ethylene in fruit ripening has the valve margin is required to degrade DELLA been reviewed many times (most recently in proteins. In the absence of GA, DELLA pro- References 74 and 56) and is therefore covered teins would otherwise interact with ALC pro- only briefly here. Fleshy fruits have historically by Universidad Veracruzana on 01/08/14. For personal use only. teins to inhibit ALC from regulating its target been divided into two classes: climacteric genes (4). (e.g., tomato, apples, and banana) and noncli-

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org macteric (e.g., grape, strawberry, and citrus). Climacteric fruits show a burst of respiration at Hormonal and Genetic Regulation the onset of ripening along with a large rise in of Maturation and Ripening ethylene production. Ripening in climacteric in Fleshy Fruits fruits can also be initiated by exposure to In tomato and grape, levels of free IAA, the exogenous ethylene. In nonclimacteric fruits, most abundant auxin, decline prior to the on- the respiratory increase is absent and ethylene set of ripening, and at the same time levels of does not appear to be critical for the ripening the “inactive” IAA–amino acid conjugate IAA- process. Direct evidence that ethylene is critical Asp increase substantially. Similar proﬁles of for the induction of ripening in climacteric fruit free IAA and IAA conjugates have also been came from work with tomato, where antisense reported in pepper, banana, muskmelon, and genes were used to suppress the expression of strawberry (9). The IAA-Asp is generated from ACO1 and ACS2, which encode ACC oxidase

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(ACO) and ACC synthase (ACS), respectively, (rin), nonripening (nor), and Colorless nonripening the major enzymes involved in ethylene (Cnr). These mutant loci all harbor transcrip- biosynthesis (56). Autocatalytic ethylene tion factors. RIN is encoded by a member of biosynthesis (system-2 ethylene biosynthesis; the SEPALLATA4 (SEP4) clade of MADS-box see 74) is operational during ripening; this genes (159), NOR is a member of the NAC- involves new forms of ACO and ACS that domain transcription factor family (50), and produce much higher levels of ethylene and CNR is encoded by an SBP-box gene, targets of are not subject to autoinhibition. Ethylene is which are likely to include the promoters of the then perceived by a family of copper-binding SQUAMOSA clade of MADS-box genes (95). membrane-associated receptors, several of The MADS-RIN gene is necessary for ripen- which—tomato ETHYLENE RESPONSE4 ing in tomato (159) and the rin mutation im- (LeETR4), LeETR6, and NR [which results pacts virtually all ripening pathways, which in the phenotype of the Never-ripe (Nr) supports its role as a master regulator of the tomato mutant]—show signiﬁcantly increased ripening process (96). Chromatin immunopre- expression at the onset of ripening (74). The cipitation experiments indicate that MADS- receptors interact with a Raf kinase–like pro- RIN directly controls the expression of a wide tein, constitutive triple response1 (CTR1), and range of other ripening-related genes, target- repress ethylene responses. When the recep- ing the promoters of genes involved in (a)the tors bind ethylene, this inhibition is relieved biosynthesis and perception of ethylene, such and a signaling process leads to the ethylene as LeACS2, LeACS4, NR,andE8;(b) cell wall response (56, 74). This involves activation of metabolism, such as polygalacturonase (PG), the ETHYLENE INSENSITIVE3 (EIN3) galactanase (TBG4), and expansins (LeEXP1); and EIN3-like (EIL) transcription factors by (c) carotenoid formation, such as phytoene syn- EIN2. In the nonclimacteric pepper fruit, thase (PSY1); (d ) aroma biosynthesis, such as EIL-like genes are induced during ripening lipoxygenase (Tomlox C), alcohol dehydroge- (81), suggesting common systems for down- nase (ADH2), and hydroperoxidelyase (HPL); stream signal transduction in climacteric and and (e) the generation of ATP, such as phos- nonclimacteric fruits, which in the latter occurs phoglycerate kinase (PGK) and the promoter in the absence of ethylene biosynthesis. In of MADS-RIN itself (47, 96, 117). MADS-RIN climacteric fruit, at least, ethylene production is also involved in suppressing the expression enhances the expression of some regulatory of most ARF genes (78) and therefore auxin- and structural genes. related gene expression. Ethylene does not act to regulate ripening In tomato, MADS-RIN is involved in by Universidad Veracruzana on 01/08/14. For personal use only. in isolation, but rather acts in concert with switching on system-2 ethylene through the in- other plant hormones. Lin et al. (85) identi- duction of LeACS2, which encodes ACS (96).

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org ﬁed a tetratricopeptide (TPR) repeat protein, The conversion of ACC to ethylene, however, SlTPR1, from tomato that interacts with the requires ACO1. The ACO1 gene does not ap- ethylene receptors LeETR1 and NR. Overex- pear to be under the direct control of MADS- pression of SlTPR1 in tomato enhances ethy- RIN, but its expression is governed by LeHB1, lene responses while causing reduced expres- a gene encoding a tomato homeobox protein. sion of the early auxin-responsive gene IAA9. LeHB1 stimulates ethylene synthesis by acti- vating the transcription of ACO1. Inhibition Transcriptional regulators of ripening in of LeHB1 using virus-induced gene silencing tomato. A major breakthrough in dissecting (VIGS) inhibits ripening and greatly reduces the transcriptional control of tomato ripening ACO1 levels. The LeHB1 gene is expressed at was the identiﬁcation of genes underlying rare higher levels in developing fruits, and the levels mutations that completely abolish the normal of expression decrease at the onset of ripening ripening process, including ripening inhibitor (86).

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MADS-RIN binding to promoter targets gene expression. A study of the expression of occurs throughout ripening (96). The action ARF genes during fruit development in the of MADS-RIN to induce the transcription of rin mutant and wild-type fruits indicated that ripening-related genes is also dependent on the MADS-RIN normally suppresses the expres- presence of the CNR gene product or a CNR- sion of most ARFs (78). These data point to regulated gene product (96). The promoters of a control system involving the removal of auxin the NOR, CNR, HB1,andTDR4 genes are also by conjugation and then repression of ARFsby targets for MADS-RIN, and MADS-RIN can the presence of MADS-RIN. form heterodimers with other MADS-box tran- Unraveling the transcriptome network con- scription factors such as TAGL1 and TAG1 of trolling fruit ripening in tomato has revealed the AGAMOUS (AG) clade and TDR4 of the some striking parallels with the regulatory cir- SQUAMOSA clade (158). This indicates that cuits in dry fruit (Figure 4). Similar MADS-box MADS-RIN exerts its control over ripening in transcription factors play a central role in both cooperation with a range of other regulatory fruit types, and in some cases they seem to be di- factors. TAGL1 is upregulated during tomato rectly orthologous (e.g., SHP1/2 and TAGL1). ripening, and its suppression inhibits normal There are also some major differences between ripening. This occurs partly through inhibi- the molecular events. In dry fruits, lignification tion of ethylene biosynthesis, and in TAGL1- follows cell division, whereas in fleshy fruits, silenced lines it appears to occur predominantly cell expansion is observed. Also, in Arabidop- through direct ACS2 suppression. Indeed, tran- sis there does not appear to be a fruit-related sient promoter-binding studies indicate direct MADS-RIN ortholog. interactions with ACS2. TAGL1 needs RIN for lycopene accumulation, with LYC-B and CYC- Control of color and texture changes. A B upregulated in TAGL1 RNAi lines. Addition- systems biology approach to the tomato tran- ally, TAGL1 appears to regulate some cell wall scriptome and metabolome during ripening has activities in a RIN-independent manner. It also led to the identification of a putative carotenoid appears to be linked to the phenyl propanoid modulator, SlERF6 (80). Reduced expression pathway and activates the flavonoid pathway. of SlERF6 by RNAi enhanced both carotenoid TAGL1 RNAi fruit also have thin pericarps, and and ethylene levels during ripening. The upregulation produces fleshy ripening sepals. majority of genes substantially influenced by This implicates TAGL1 in not only ripening SlERF6 repression were upregulated, indicat- but also the development of fleshiness in tomato ing that the primary function of SlERF6 occurs (68, 158). via negative regulation. SlERF6 was responsive by Universidad Veracruzana on 01/08/14. For personal use only. RNAi suppression of AP2—which belongs to ethylene and may be a component of a to the AP2/ETHYLENE RESPONSE FAC- feedback restriction in ethylene production

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org TOR (ERF) family of transcription factors (18, during ripening, similar to SlAP2 (80). A 72) and acts downstream of RIN, NOR, and small number of fruit high-pigment mutants CNR—results in rapid softening and earlier have been described in tomato, including high ripening. Evidence indicates that AP2 is a neg- pigment1 (hp1) [a lesion in UV-DAMAGED ative regulator of ripening in tomato (18) that DNA BINDING PROTEIN1 (DDB1) (89)] and operates in a negative-feedback loop with CNR, hp2 [a mutation in tomato DE-ETIOLATED1 as illustrated by the observation that in the (DET1)] (107). These genes are involved in the pericarps of AP2 RNAi fruits, mRNA levels of suppression of light responses in the absence CNR were elevated. In addition, it has been of light, and for DET1, suppression occurs by demonstrated that CNR can bind to the pro- a molecular mechanism involving chromatin moter of AP2 in vitro (72). Interestingly, AP2 remodeling (24). Coordinated upregulation of RNAi fruits show enhanced GH3 gene expres- core metabolic processes is responsible for the sion (72), likely linking AP2 to auxin-related high-pigment phenotype in the DET1 lines

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a ening. Modulation of genes encoding two ripening-specific N-glycoprotein-modifying enzymes—α-mannosidase and β-D-N- acetylhexosaminidase—reduces the rate of softening and enhances fruit shelf life (102). More than 50 cell wall structure–related genes TDR4 AP2 TAGL1 PSY1 (SHP) (FUL) show expression changes in ripening tomato LOXC fruits (151), and texture involves complex RIN NOR CNR (SEP4) EXP quantitative trait loci (13). Shelf life is also related to water loss from the mature fruits. PG HB1 Cuticle properties are critical for maintain- ACS ing fruit integrity postharvest. Delayed Fruit ACO Ethylene Deterioration (DFD) mutant tomato fruits show remarkably prolonged resistance to Activation Repression postharvest desiccation and remain firm for b many months after harvest (127), and analyses of cutin-deficient tomato mutants indicate the AP2 SHP importance of waxes (67; see also 64). FUL RPL IND Tomato as a model for understanding ripening in other fleshy-fruited species. PG In banana—which, like tomato, is a climacteric fruit—SEP3-class MADS-box genes show ripening-related expression (35) and are prob- ably necessary for normal ripening. In straw- 20 µm berry, a nonclimacteric fruit, a SEP1/2-class Figure 4 gene is needed for normal development and ripening (133). VmTDR4, the bilberry ortholog Ripening network in fleshy fruits and comparison with events in the dehiscence of dry fruits. (a)Major of the TDR4 gene in tomato, is involved in the known regulators of ripening in tomato. The blue regulation of anthocyanin biosynthesis in the circles are transcription factors; the yellow labels are fruit flesh (69), and in apple, MADS2 expression genes where orthologs are also found in dry is associated with fruit firmness (12). MADS- dehiscent fruits. Downstream effectors are shown in box and NAC transcription factors are associ- by Universidad Veracruzana on 01/08/14. For personal use only. white boxes. Precisely how the gene products of NOR, CNR,andRIN interact is unknown, so dashed ated with the ripening process in the drupe of green lines are shown between those. (b) Brassica pod the oil palm (152).

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org and dehiscence zone, illustrating a dry-fruit network using information obtained in Arabidopsis. Image of Epigenetics. The lesion responsible for the tomato fruit with ripening inhibited by silver Cnr mutation is due to an epigenetic change thiosulfate on the left side kindly provided by Don Grierson and Kevin Davies. leading to hypermethylation of the CNR promoter and inhibition of gene expression and (38). Upregulation of a Golden 2–like transcrip- ripening in the mutant (95). Additionally, in tion factor in tomato has also been shown to normal fruit development, at least in the tomato Epigenetics: the elevate levels of chlorophyll and carotenoids, cultivar Liberto, the promoter of CNR appears study of heritable and a lesion in this gene is responsible for the to be demethylated in a speciﬁc region just prior variation involving uniform-ripening phenotype (116). to the onset of ripening. mechanisms other than changes in the Shelf life is important in tomato and A further level of regulation controlling fruit DNA sequence of an other fruits. This trait is inﬂuenced by many ripening occurs through the presence of small organism processes, including the rate of fruit soft- RNAs (sRNAs). These include microRNAs

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(miRNAs) and other sRNAs of unknown func- global human diet) and to selective breeding tion. The CNR 3 untranslated-region sequence (161). For these reasons, most modern dietary contains a miRNA binding site that is comple- recommendations include increased consump- mentary to miR156 /157 (23). Deep sequencing tion of fresh or whole fruits and vegetables. The of the sRNAome of developing tomato fruits, role of plants in human health is the subject of covering the period between closed flowers and another review (98), but what is beneficial about ripened fruits through the profiling of sRNAs fruit consumption? at 10 time points, has revealed that thousands of Fruits such as eggplant, mango, and okra are non-miRNA sRNAs are differentially expressed good sources of soluble fiber, which has been during fruit development and ripening (106). shown experimentally to lower the glycemic Some of these sRNAs are derived from trans- index of foods and to have beneficial effects posons, but many map to regions in protein- on type 2 diabetes, cardiovascular disease, and coding genes, including well-defined areas of obesity (66, 73, 79, 103). Fruits are also rich the noncoding regulatory regions (151). Spe- in fructose (which constitutes 20–40% of the cific classes of sRNAs seem more abundant at available carbohydrates in wild fruit) and in- certain stages of development, e.g., 24-mers trinsic sugars; these are not subject to restric- during ripening. The function of these changes tions in dietary recommendations because their in sRNA patterns is not known, but they may concentrations are not high enough to have ad- play an important role in the ripening process. verse health outcomes (94). Fruits generally also contain high levels of phytonutrients, and include carotenoids, polyphenols (flavonoids, stil- FRUITS AND THE HUMAN DIET benes), plant sterols, vitamins, and polyunsatu- The human genome evolved in the context rated fatty acids. of the diet prevailing before the introduction Some fruits are rich in carotenoids, which of agriculture and animal husbandry approxi- are thought to attract animals as dispersers mately 10,000 years ago, when humans were through their bright colors (for example, hunter-gatherers; diets were rich in fruits, veg- lycopene in tomato; capsanthin, β-carotene, etables, and protein and low in fats and starches lutein, and violaxanthin in red pepper; ly- (33). For primates such as chimpanzees and copene and β-carotene in red grapefruit; orangutans, more than 75% of their diet by and β-carotene, α-carotene, and lutein in weight is fresh fruit, and the assumption is that mangoes). Lycopene is a methyl-branched our primate ancestors had similar diets. Fruit carotenoid that has no provitamin A activity. It is also common in the diet of modern hunter- is a potent lipophilic antioxidant, with greater by Universidad Veracruzana on 01/08/14. For personal use only. gatherers. antioxidant activity than other carotenoids, The 10,000 years (∼360 generations) since and has been shown to be protective against

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org the first cultivation of cereals has not been cardiovascular disease and prostate cancer (43). enough time for humans to adapt to starchier, Intervention and epidemiological studies have cereal-based diets with much higher amounts linked β-carotene consumption to enhanced of fat and lower amounts of fresh fruit and veg- protection against cardiovascular disease, etables, and it has been suggested that many including cerebral infarction, and resistance chronic diseases result from our evolutionary to low-density lipoprotein oxidation, ischemic discordance with modern diets (21). Levels stroke, and carotid atherosclerosis (7, 43, of phytonutrients—compounds in plant-based 121). foods that play potentially beneficial roles in Fruits are rich sources of polyphenols that the prevention and treatment of disease—in the have gained significant recognition recently as diet have dropped significantly owing to a re- being important phytonutrients, reducing the duced variety of plants consumed (currently, risk of chronic diseases such as cardiovascu- just 17 plant species constitute 90% of the lar disease, metabolic syndrome, cancer, and

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obesity. Anthocyanins represent a subset of replacing calorie-dense food) helps maintain a flavonoids with particularly high antioxidant ca- healthy weight and reduce the risk of a wide pacity and strong health-promoting effects. As range of cancers (150, 163) and cardiovascu- High-throughput part of the human diet, they offer protection lar disease (59, 60, 82). Consequently, dietary sequencing against cancer, inhibiting both the initiation improvement by increasing fruit consumption technologies: and progression stages of tumor development or by improving fruit to contain higher lev- methods that involve (154), reducing inflammatory inducers of tumor els of fiber or phytonutrients should have a producing millions of initiation, suppressing angiogenesis, and min- positive impact on the incidence and progres- sequences from DNA samples in a parallel imizing cancer-induced DNA damage in ani- sion of chronic disease. Such improvement of process mal disease models. Anthocyanins also protect fruit crops could be carried out through genetic against cardiovascular disease and age-related modification (11) or marker-assisted selection degenerative diseases associated with metabolic using existing variation. syndrome (63, 119), have anti-inflammatory activity (134), promote visual acuity (101), and hinder obesity and diabetes (154). Inverse cor- CROP IMPROVEMENT relations between consumption of flavonol-rich High-throughput sequencing technologies diets and the occurrence of cardiovascular dis- have provided a powerful new set of tools ease, certain cancers, and age-related degener- to reveal genetic and epigenetic variation ative diseases (62, 75, 105, 130, 138) have been on a genome-wide scale and therefore new shown in human epidemiological studies as well insights into the evolution of genomes and trait as by data from cell-based assays and feeding variation. Fruit crop genomes that have been trials with animals. sequenced include grapevine (Vitis vinifera) Another important group of plant-based (70), apple (Malus × domestica) (157), diploid bioactive polyphenols is the hydroxycinnamic strawberry (Fragaria vesca) (135), tomato acid esters, of which chlorogenic acid is the (Solanum lycopersicum) (151), and banana (Musa major soluble phenolic in solanaceous species acuminata) (28). These resources will underpin such as potato, tomato, and eggplant as well as advances in the breeding of fruit crops by (a) in coffee. Chlorogenic acid is one of the most greatly facilitating marker-assisted selection abundant polyphenols in the human diet and is and allowing efficient cloning of genes under- the major antioxidant in the average developed- pinning quantitative trait loci, (b) providing world diet. It has significant antioxidant activ- the reference genomes for rapid allele mining ity, and consumption can limit glucose absorp- in crop wild relatives (87), (c) providing a tion and possibly weight gain (146). guide for direct sequencing of monogenic by Universidad Veracruzana on 01/08/14. For personal use only. Epicatechins are the major polyphenolic mutants, and (d ) maximizing opportunities compounds in green tea, and the most sig- to optimize reverse-genetics tools such as

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org nificant active component is thought to be targeting-induced local lesions in genomes epigallocatechin gallate. Cell, animal, and hu- (TILLING) for gene functional studies (142). man studies have shown that green tea ex- Genome-wide information also allows rapid tract/epicatechins prevent cancer development, analyses of gene structure, binding-site motifs, particularly prostate cancer (22, 31). Similar ef- and gene regulatory regions. fects may be gained by consumption of fleshy In the future, high-throughput sequencing fruits such as cranberry, blueberry, and grape or technologies will allow routine screening by consumption of berry-juice products; these of crop epigenomes and therefore permit have relatively high levels of catechins and epi- detection of epigenetic variation that impacts catechins, which also protect against cardiovas- phenotypes. Additionally, translational biology cular disease (27). from models to crop species has clear utility Dietary intervention studies support the in enhancing important crop traits; e.g., view that consumption of fruit (especially when fine-tuning the expression of the value margin

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identity gene IND in Brassica gives a potentially combination with direct genetic modiﬁcation useful partial dehiscence phenotype (52). provides a powerful route for a massive step Harnessing variation in crop wild relatives in change in crop improvement.

SUMMARY POINTS 1. True fruits are found only in the angiosperms, or flowering plants. They are often defined as structures derived from a mature ovary containing seeds, but many structures we call fruit are composed of a variety of tissues. Fruit structures can be dehiscent or indehiscent, can have a dry or fleshy exterior, and include grains, nuts, capsules, and berries. 2. Recent work on the model plant Arabidopsis and on tomato nonripening mutants has uncovered the complex high-level regulatory network controlling fruit maturation and ripening. Striking parallels have been revealed between the molecular circuits in dry fruits and those in fleshy fruits. In both types, similar MADS-box transcription factors play a central role, and in some cases they seem to be directly orthologous. 3. Tomato is a good model for understanding aspects of the molecular framework controlling ripening in other fleshy fruits. Classes of transcription factors controlling tomato ripening have been shown to govern this process in other fleshy-fruit-bearing species. 4. The human genome evolved in the context of the diet prevailing before the introduction of agriculture and animal husbandry approximately 10,000 years ago, when humans were hunter-gatherers; diets were rich in fruits, vegetables, and protein and low in fats and starches. Fruits provide vitamins, minerals, and phytochemicals that are essential for human health. 5. The genomes of a variety of fleshy-fruited species have been sequenced and provide guides for revealing previously hidden genetic and epigenetic variation that will open a new frontier for crop improvement.

FUTURE ISSUES by Universidad Veracruzana on 01/08/14. For personal use only. 1. Can predictive models of the ripening regulatory network be generated for tomato and other ﬂeshy- and dry-fruited species? And can major ripening processes—e.g., texture

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org and color development—be separated to allow better control over the process? 2. Is it possible to modify regulatory networks to easily transition from a dry- to ﬂeshy-fruit phenotype or vice versa? 3. One of the best-characterized natural epigenetic mutations was discovered in tomato. To what extent is epigenetic variation responsible for controlling important quality traits in crops and crop wild relatives?

DISCLOSURE STATEMENT C.M. is a director of Norfolk Plant Sciences, an SME for the development of phytonutrient- enriched fruits and vegetables.

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ACKNOWLEDGMENTS We wish to acknowledge the support of the UK Biotechnology and Biological Sciences Research Council to G.B.S. (BB/G02491X) and the US National Science Foundation Planetary Biodiversity Initiative to S.K. (DEB-0316614).

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Annual Review of Plant Biology Contents Volume 64, 2013

Benefits of an Inclusive US Education System Elisabeth Gantt pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp1 Plants, Diet, and Health Cathie Martin, Yang Zhang, Chiara Tonelli, and Katia Petroni ppppppppppppppppppppppppp19 A Bountiful Harvest: Genomic Insights into Crop Domestication Phenotypes Kenneth M. Olsen and Jonathan F. Wendel pppppppppppppppppppppppppppppppppppppppppppppppp47 Progress Toward Understanding Heterosis in Crop Plants Patrick S. Schnable and Nathan M. Springer pppppppppppppppppppppppppppppppppppppppppppppp71 Tapping the Promise of Genomics in Species with Complex, Nonmodel Genomes Candice N. Hirsch and C. Robin Buell pppppppppppppppppppppppppppppppppppppppppppppppppppppp89 Understanding Reproductive Isolation Based on the Rice Model Yidan Ouyang and Qifa Zhang pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp111 Classification and Comparison of Small RNAs from Plants Michael J. Axtell pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp137 Plant Protein Interactomes by Universidad Veracruzana on 01/08/14. For personal use only. Pascal Braun, Sébastien Aubourg, Jelle Van Leene, Geert De Jaeger, and Claire Lurin ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp161

Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org Seed-Development Programs: A Systems Biology–Based Comparison Between Dicots and Monocots Nese Sreenivasulu and Ulrich Wobus ppppppppppppppppppppppppppppppppppppppppppppppppppppp189 Fruit Development and Ripening Graham B. Seymour, Lars Østergaard, Natalie H. Chapman, Sandra Knapp, and Cathie Martin ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp219 Growth Mechanisms in Tip-Growing Plant Cells Caleb M. Rounds and Magdalena Bezanilla pppppppppppppppppppppppppppppppppppppppppppppp243 Future Scenarios for Plant Phenotyping Fabio Fiorani and Ulrich Schurr pppppppppppppppppppppppppppppppppppppppppppppppppppppppppp267

v PP64-frontmatter ARI 25 March 2013 10:21

Microgenomics: Genome-Scale, Cell-Specific Monitoring of Multiple Gene Regulation Tiers J. Bailey-Serres ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp293 Plant Genome Engineering with Sequence-Specific Nucleases Daniel F. Voytas pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp327 Smaller, Faster, Brighter: Advances in Optical Imaging of Living Plant Cells Sidney L. Shaw and David W. Ehrhardt ppppppppppppppppppppppppppppppppppppppppppppppppp351 Phytochrome Cytoplasmic Signaling Jon Hughes pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp377 Photoreceptor Signaling Networks in Plant Responses to Shade Jorge J. Casal ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp403 ROS-Mediated Lipid Peroxidation and RES-Activated Signaling Edward E. Farmer and Martin J. Mueller ppppppppppppppppppppppppppppppppppppppppppppppp429 Potassium Transport and Signaling in Higher Plants Yi Wang and Wei-Hua Wu ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp451 Endoplasmic Reticulum Stress Responses in Plants Stephen H. Howell pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp477 Membrane Microdomains, Rafts, and Detergent-Resistant Membranes in Plants and Fungi Jan Malinsky, Miroslava Opekarová, Guido Grossmann, and Widmar Tanner ppppppp501 The Endodermis Niko Geldner pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp531 Intracellular Signaling from Plastid to Nucleus Wei Chi, Xuwu Sun, and Lixin Zhang ppppppppppppppppppppppppppppppppppppppppppppppppppp559

by Universidad Veracruzana on 01/08/14. For personal use only. The Number, Speed, and Impact of Plastid Endosymbioses in Eukaryotic Evolution Patrick J. Keeling ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp583 Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org Photosystem II Assembly: From Cyanobacteria to Plants J¨org Nickelsen and Birgit Rengstl pppppppppppppppppppppppppppppppppppppppppppppppppppppppppp609 Unraveling the Heater: New Insights into the Structure of the Alternative Oxidase Anthony L. Moore, Tomoo Shiba, Luke Young, Shigeharu Harada, Kiyoshi Kita, and Kikukatsu Ito ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp637 Network Analysis of the MVA and MEP Pathways for Isoprenoid Synthesis Eva Vranov´a, Diana Coman, and Wilhelm Gruissem ppppppppppppppppppppppppppppppppppp665

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Toward Cool C4 Crops Stephen P. Long and Ashley K. Spence pppppppppppppppppppppppppppppppppppppppppppppppppppp701 The Spatial Organization of Metabolism Within the Plant Cell Lee J. Sweetlove and Alisdair R. Fernie ppppppppppppppppppppppppppppppppppppppppppppppppppp723 Evolving Views of Pectin Biosynthesis Melani A. Atmodjo, Zhangying Hao, and Debra Mohnen ppppppppppppppppppppppppppppppp747 Transport and Metabolism in Legume-Rhizobia Symbioses Michael Udvardi and Philip S. Poole pppppppppppppppppppppppppppppppppppppppppppppppppppppp781 Structure and Functions of the Bacterial Microbiota of Plants Davide Bulgarelli, Klaus Schlaeppi, Stijn Spaepen, Emiel Ver Loren van Themaat, and Paul Schulze-Lefert ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp807 Systemic Acquired Resistance: Turning Local Infection into Global Defense Zheng Qing Fu and Xinnian Dong pppppppppppppppppppppppppppppppppppppppppppppppppppppppp839

Indexes

Cumulative Index of Contributing Authors, Volumes 55–64 ppppppppppppppppppppppppppp865 Cumulative Index of Article Titles, Volumes 55–64 ppppppppppppppppppppppppppppppppppppp871

Errata

An online log of corrections to Annual Review of Plant Biology articles may be found at http://www.annualreviews.org/errata/arplant by Universidad Veracruzana on 01/08/14. For personal use only. Annu. Rev. Plant Biol. 2013.64:219-241. Downloaded from www.annualreviews.org

Contents vii