The role of tomato wild relatives in breeding disease-free varieties

Hamid Khazaei; Adithya Madduri

doi:10.46265/genresj.PSES6766

The role of tomato wild relatives in breeding disease-free varieties

Hamid Khazaei ✉ ¹ , Adithya Madduri ¹

1 World Vegetable Center, Shanhua, Taiwan

Abstract

Cultivated tomato (Solanum lycopersicum) is one of the most economically important and widely grown vegetable crops worldwide. However, tomato plants are often affected by biotic and abiotic stresses that reduce yield and affect fruit quality. Phenotypic diversity is evident in cultivated tomatoes, particularly for horticultural traits, but genetic diversity is rather narrow. Major disease resistance genes for different pathogens such as viruses, fungi, bacteria and nematodes are mainly derived from wild tomato species and introgressed into cultivated tomatoes. Here, we list the major disease and insect-pest resistance genes identified in S. pimpinellifolium, S. habrochaites, S. peruvianum, S. chilense, S. pennellii, S. galapagense, S. arcanum and S. neorickii with perspective on the gap between current knowledge on tomato wild relatives and the knowledge that is needed.

Keywords

Tomato, crop wild relatives, disease resistance, genomics, plant genetic resources, plant breeding

Tomato wild relatives

Crop wild relatives (CWRs) are potential sources of allelic variation useful to overcome biotic and abiotic stresses as they often grow and reproduce in marginal habitats (Bohra et al., 2021; Ortiz, 2015). Tomato wild relatives are native to South America, distributed from the coastal region of Ecuador to northern Chile, including the Galápagos Islands (Darwin, Knapp, & Peralta, 2003). These regions have extremely varied environments within short distances due to differences in altitude (Andean geography) and diverse ecological habitats, which led to local adaptation and generation of large genetic diversity among (Figure 1) and within wild tomato species. Solanum section Lycopersicon (Mill.) Wettst. consists of cultivated tomato (S. lycopersicum) and 12 wild relatives (Ramírez-Ojeda et al., 2021). The Tomato Genetics Resource Center (C.M. Rick TGRC, University of California-Davis, USA, https://tgrc.ucdavis.edu/) hosts the largest genetic stocks of wild tomato collections, with over 900 accessions. The largest collection belongs to accessions of S. pimpinellifolium (~300) followed by S. habrochaites (~120), S. peruvianum (~100), S. chilense (~100), and S. pennellii (~50), respectively (Table 1). The World Vegetable Center (WorldVeg, Taiwan https://genebank.worldveg.org/#/) and the United States Department of Agriculture, Agricultural Research Service (USDA-ARS, https://www.ars-grin.gov/) genebanks also maintain the second and third largest wild tomato collections, respectively (Table 1). However, the majority of their wild tomato collection was originally obtained from the TGRC collection. Furthermore, these genebanks harbour an extensive collection of introgression lines derived from different tomato wild species (Ebert & Schafleitner, 2015).

Table 1: Genetic resources of tomato wild relatives maintained by the Tomato Genetics Resource Center (C.M. Rick TGRC), World Vegetable Center (WorldVeg), and the United States Department of Agriculture, Agricultural Research Service (USDA-ARS) genebanks (data accessed on June 23, 2022).

Species	No. of accessions per genebank
	TGRC	WorldVeg	USDA-ARS
S. pimpinellifolium	290	342	338
S. habrochaites	120	139	49
S. peruvianum	69	116	11
S. chilense	115	46	1
S. pennellii	47	59	5
S. corneliomulleri	53	10	12
S. neorickii	47	12	8
S. galapagense	28	27	4
S. arcanum	45	4	3
S. cheesmaniae	12	17	5
S. chmielewskii	16	11	0
S. lycopersicoides	23	5	0
S. sitiens	13	5	2
S. huaylasense	16	0	0
S. ochranthum	7	0	2
S. juglandifolium	5	1	0

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/43bef657-adfd-444f-a4a8-8a97ab330e50/image/c0135f39-b9c8-4f50-815e-6df909ebe5df-ufigure1new.jpg — **Figure 1:** Diversity in fruit colour and leaf shape of some tomato wild relatives. From left to right: *S. pimpinellifolium* (LA1269), *S. peruvianum* (L00887-3), *S. chilense* (LA2737B) and *S. galapagense* (VI063177). The size of the marker is 14cm × 1cm. Photo credit: Hamid Khazaei

Utilization of tomato wild relatives for biotic stress breeding

Domestication has increased the phenotypic diversity of cultivated tomatoes but may have narrowed their resistance to biotic and abiotic constraints as selection ensued (Vu, Das, Tran, Hong, & Kim, 2020). Tomato wild relatives germplasm harbour natural resistance to various diseases and insect pests. Sources of genetic resistance to many of the biotic stresses faced by cultivated tomatoes have been identified in some accessions of wild tomato species that have been historically used to introduce resistance (R) genes into cultivated tomato varieties. It should be noticed that there is genetic diversity for biotic resistance response within tomato wild species, and only a few accessions within each species have been identified as sources of resistance ( (Ebert et al., 2015) and references). We list major R genes found in and introgressed from wild tomato species into cultivated tomatoes in Table 2, along with information about their causal pathogens as footnotes. For example, the R genes/alleles conferring resistance to the begomoviruses that cause tomato yellow leaf curl diseases (called Ty genes), were found in wild tomato species. Most tomato advanced lines grown in tropical and subtropical regions of the world carry at least one source of Ty resistance genes (Ty-1/Ty-3) or multiple Ty genes (Ty-2, ty-5, Ty-6). The pyramiding of Ty genes into one line leads to broad and probably more durable resistance to begomoviruses. Likewise, R genes for late blight (caused by Phytophthora infestans, Ph genes) and fusarium wilt (caused by Fusarium oxysporum, I genes) also originated from wild tomatoes (Table 2). These genes are also frequently present in the modern tomato lines worldwide. Some important major QTLs (quantitative trait locus) such as Bwr and EB, conferring bacterial wilt (caused by Ralstonia spp.) and early blight (caused by Alternaria linariae) resistance, were first introgressed to adapted cultivated tomato cultivars from S. pimpinellifolium and later uncovered and genetically mapped. Some R genes (Rx-1, -2 and -3) for bacterial spot resistance (caused by several species of gram-negative bacteria in the genus Xanthomonas) were also derived from S. pimpinellifolium via cultivated tomato. Several R genes against important pathogens in tomato have mainly been introgressed, from the wild species S. pimpinellifolium, S. habrochaites, S. peruvianum, S. chilense and S. pennellii, into modern tomato varieties (Table 2). However, most tomato breeding programmes focus on S. pimpinellifolium due to its red fruit colour (Figure 1) and its close relationship to cultivated tomato, which allows breeders to easily obtain interspeciﬁc crosses. That is probably why most of the R genes have already been identified in this species.

Table 2: List of major biotic resistance genes incorporated into cultivated tomatoes (Solanum lycopersicum) from wild relatives of tomato and S. lycopersicum var. cerasiforme. Causative agents for the listed diseases are included in footnotes.

Species	R-genes’ contribution	Disease/Insect pest	References
S. pimpinellifolium L.	I and I-2	Fusarium wilt¹	Stall and Walter (1965); reviewed in Chitwood-Brown, Vallad, Lee, and Hutton (2021)
S. pimpinellifolium L.	Ph-1, Ph-2, Ph-3 and Ph-5	Late blight²	Bonde and Murphy (1952); Gallegly and Marvel (1955); (AVRDC, 1994); Foolad, Merk, Ashrafi, and Kinkade (2006)
	EB-5 and EB-9	Early blight^3*	Anderson, Zitter, Jong, Francis, and Mutschler (2021)
	Bwr-6 and Bwr-12	Bacterial wilt^4*	Wang et al. (2013)
	Rx-1, Rx-2 and Rx-3	Bacterial spot^5*	Yu, Wang, Stall, and Vallejos (1995); reviewed in (Adhikari, Adhikari, Louws, & Panthee, 2020)
	Rx-4	Bacterial spot	Robbins, Darrigues, Sim, Masud, and Francis (2009)
	Sm	Gray leaf spot⁶	Parlevliet (2002)
	Cf genes (except Cf-4 and Cf-5)	Leaf mold⁷	Bailey (1950); reviewed in Scott and Gardner (2007)
	Sw-1(a and b), Sw-2, Sw-3 and Sw-4	TSWV⁸	(Finlay, 1953); Roselló, Díez, and Nuez (1998); (Zhu et al., 2017); reviewed in Qi et al. (2021)
	Pto	Bacterial speck⁹	Pitblado and Kerr (1980)
	Cmm genes	Bacterial canker¹⁰	Forster and Echandi (1972); Sotirova, Bogatsevska, and Stamova (1994); Sen, Manrique, Kabaş, and Visser (2021)
S. habrochaites S. Knapp and D. M. Spooner	Ph-4	Late blight	Lough (2003)
S. habrochaites S. Knapp and D. M. Spooner	Cf-4	Leaf mold	Stevens and Rick (1986)
	Ty-2	TYLCV¹¹	Hanson, Green, and Kuo (2006)
	Tm-1	ToMV¹²	(Pelham, 1966)
	Ol-1/Ol-3, and Ol-5	Powdery mildew¹³	(Beek, G, & Lindhout, 1994); Huang, Putte, Meer, Meijer-Dekens, and Lindhout (2000); (Bai et al., 2005)
	Cmm genes	Bacterial canker	Forster et al. (1972); Francis et al. (2001); Coaker and Francis (2004); Sotirova et al. (1994)
	Rbcq genes	Gray mould¹⁴	Have, Berloo, Lindhout, and Kan (2007); (Finkers et al., 2007; Finkers et al., 2007)
S. peruvianum L.	ty-5	TYLCV	Hutton, Scott, and Schuster (2012)
	Sw-5 and Sw-6	TSWV	Giordano, Avila, Charchar, Boiteux, and Ferraz (2000); Rosello, Ricarte, Diez, and Nuez (2001)
	Mi genes	Root-knot nematodes¹⁵	Smith (1944); reviewed in El-Sappah et al. (2019)
	Tm-2, Tm-2 ² and Tm-2a	ToMV	(Soost, 1963); (Ganal & Tanksley, 1996) and Tanksley and Nelson (1996)
	Ve	Verticillium wilt¹⁶	Diwan, Fluhr, Eshed, Zamir, and Tanksley (1999)
	Frl	Fusarium crown¹⁷	Vakalounakis, Laterrot, Moretti, Ligoxigakis, and Smardas (1997)
S. chilense (Dunal) Reiche	Ty-1/Ty-3a, Ty-4, and Ty-6	TYLCV	Zamir et al. (1994); Ji, Schuster, and Scott (2007); Ji, Scott, Schuster, and Maxwell (2009); Gill et al. (2019)
	Sw-7	TSWV	Stevens, Scott, and Gergerich (1994)
	Cmm genes	Bacterial canker	Sotirova et al. (1994)
	Lv	Powdery mildew	Yordanov, Stamova, and Stoyanova (1975); Chunwongse, Doganlar, Crossman, Jiang, and Tanksley (1997)
	-	Gray mould	Have et al. (2007)

Species	R-genes' contribution	Disease/Insect pest	References
S. pennellii Correll	I-3 and I-7	Fusarium wilt	Catanzariti, Lim, and Jones (2015); (Gonzalez-Cendales, Catanzariti, Baker, Mcgrath, & Jones, 2016)
	Asc	Alternaria stem canker¹⁸	Scott et al. (2007)
	Xv-4	Bacterial spot	Astua-Monge et al. (2000)
	Acylsugar-related genes	A wide range of insects	(Leckie et al., 2016; Leckie, Jong, & Mutschler, 2012); Schilmiller, Charbonneau, and Last (2012)
S. galapagense S. C. Darwin and Peralta	Wf-1 and Wf-2	Whiteflies¹⁹	Firdaus et al. (2013); Santegoets, Bovio, Westende, Voorrips, and Vosman (2021)
S. arcanum Peralta	Ol-4	Powdery mildew	(Bai et al., 2005)
	Cmm genes	Bacterial canker	Crinò et al. (1995); Sotirova et al. (1994); Sen et al. (2013)
S. neorickii D. M. Spooner, G. J. Anderson and R. K. Jansen	V2	Verticillium wilt	(Kanagawa Agricultural Technology Center, 1999)
	-	Gray mould	Have et al. (2007); Finkers et al. (2008)
S. l. var. cerasiforme	Cf-5	Leaf mold	Dickinson, Jones, and Jones (1993); Dixon, Hatzixanthis, Jones, Harrison, and Jones (1998)
	ol-2	Powdery mildew	(Ciccarese, Amenduni, Schiavone, & Cirulli, 1998)

¹Fusarium wilt caused by fungal pathogen Fusarium oxysporum (Schlecht. emend. Snyder & Hansen). ²Late blight resistance caused by the oomycete Phytophthora infestans (Mont.) de Bary. ³Early blight is caused by fungal pathogen Alternaria spp. ⁴Bacterial wilt caused by the group of soilborne bacteria in the Ralstonia solanacearum species complex. ⁵Bacterial spot caused by several species belonging to the genus Xanthomonas. It can be caused by Xanthomonas euvesicatoria ex Doidge, X. vesicatoria ex Doidge, X. perforans, and X. gardneri Šutic. ^Early blight, bacterial wilt, and bacterial spot (Rx-1, Rx-2, and Rx-3) resistance genes are most likely derived from S. pimpinellifolium* via cultivated tomato. ⁶Gray leaf spot caused by fungal pathogen Stemphylium lycopersici (S. lycopersici). ⁷Leaf mold caused by fungal pathogen Cladosporium fulvum (syn. Passalora fulva). ⁸TSWV, tomato spotted wilt orthotospovirus (order Bunyavirales, family Tospoviridae, genus Orthotospovirus) is transmitted by Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). ⁹Bacterial speck disease caused by Pseudomonas syringae pv. tomato (Pst). ¹⁰Bacterial canker caused by Clavibacter michiganensis subsp. Michiganesis. ¹¹TYLCV, tomato yellow leaf curl virus disease. TYLCV is caused by whitefly transmitted Geminiviruses (begomoviruses). Ty-1 and Ty-3 are allelic (Verlaan et al., 2013). ¹²ToMV, tomato mosaic virus. ToMV is a member of the family tobamoviridae and belongs to the genus tobamovirus. ¹³Powdery mildew can be caused by three species of biotrophic fungal pathogens; Oidium lycopersici, Oidium neolycopersici (syn. Pseoudoidium neolycopersici), and Leveillula taurica. Ol-1 and Ol-3 are allelic (Huang et al., 2000). ¹⁴Gray mould caused by fungal pathogen Botrytis cinerea (teleomorph: Botryotinia fuckeliana). ¹⁵Root-knot nematodes can be caused by Meloidogyne incognita, M. javanica, and M. arenaria. ¹⁶Verticillium wilt caused by the biotrophic fungus Verticillium dahliae. ¹⁷Fusarium crown rot caused by F. oxysporum f. sp. radicis-lycopersici. ¹⁸Alternaria stem canker caused by fungal pathogen Alternaria alternate. ¹⁹Whitefly (Bemisia tabaci) resistance.

Challenges

The utilization of wild tomatoes in breeding programmes is not without a cost. CWRs generally show poor adaptation beyond their natural distribution range (Bohra et al., 2021). Furthermore, the introgressed gene from a wild relative into advanced lines may disrupt long-accumulated horticultural traits due to linkage drag (Tanksley et al., 1996). For example, S. galapagense has been identified as a source of insect-pest resistance (Rakha, Hanson, & Ramasamy, 2017; Vendemiatti et al., 2021). When it is crossed with cultivated tomatoes, the fruit size and setting reduce significantly, which are undesirable traits. Linkage drag can be removed by conducting backcrosses to the recurrent parents (cultivated tomato). Applications of DNA molecular markers (MAB, marker-assisted backcrossing) allow for the monitoring of the genome around the gene/locus of interest and the genetic background, speeding up the return to the recurrent parent genome (Tourrette, Falque, & Martin, 2021). Genome editing can also be used to remove the undesirable gene without having extensive backcrossing. For example, CRISPR-Cas9-based gene editing was used to overcome a linkage drag in tomato by editing the jointless-2 gene introgressed from S. cheesmaniae (Roldan et al., 2017). The World Vegetable Center is currently testing CRISPR-Cas9 to edit genes implicated with fruit size regulation in interspecific crosses between S. galapagense and cultivated tomato (Schafleitner, Lin, Khazaei, & Tsai, 2022).

Genomics-assisted breeding tools

Tomato wild relatives have more to offer.Bai, Kissoudis, Yan, Visser, and Linden (2018) stated that about 20 pathogens could be genetically controlled by resistance genes derived from a few wild species. The genome of some tomato wild species, including S. pennellii (Bolger, Scossa, Bolger, Lanz, & Maumuset, 2014; Schmidt, Vogel, Dentonet, Istace, & Wormitet, 2017), S. chilense (Stam et al., 2019), S. pimpinellifolium (Gramazio et al., 2020; Razali et al., 2018; Wang, Gao, Jia, Stravoravdis, & Hosmani, 2020) and S. lycopersicoides (Powell, Feder, Li, Schmidt, & Courtney, 2022) along with the pan-genome (Gao, Gonda, & Sun, 2019) have been assembled. These efforts have bolstered our knowledge and understanding of tomato wild species along with the genetics of resistance genes. Recent improvements in genomic resources have enabled us to track and genetically map the wild tomato genes in commercially adapted varieties (Anderson et al., 2021). The tomato community largely benefits from advanced, rich genomic resources (https://solgenomics.net/) and phenotyping tools; however, rapid generation technology (speed breeding) has not yet been developed. Robust DNA markers for major genes derived from wild relatives have been developed and widely applied in private and public breeding programmes worldwide (Foolad & Panthee, 2012; Hanson et al., 2016).

In the past, sources of important disease resistance genes in wild tomato relatives have been intensively investigated. However, the majority of R genes were discovered only in a few species (listed in Table 1). The other wild species that either are not easy to cross with cultivated tomatoes or are self-incompatible or allogamous have not contributed much to this journey (e.g. S. chmielewskii, S. corneliomulleri, S. huaylalloasense, S. juglandifolium, S. ochranthum, S. lycopersicoides and S. sitiens). Regarding these species, the literature only represents a few accessions of S. lycopersicoides being resistant to grey mould (caused by Botrytis cinerea) (Davis et al., 2009) or a few accessions of S. corneliomulleri being resistant to the TYLCV (Yan et al., 2018), but major genes/alleles from these species are yet to be reported. For some of these species, only a few accessions have been collected or are available in genebanks (Table 1). Among these species, some genomic studies were performed on S. sitiens (Chetelat et al., 2019) and S. lycopersicoides (Powell et al., 2022), which are potential sources of genes for adaptation to abiotic stresses (i.e. drought and heat stresses). Introgression lines were also developed from S. chmielewskii to study the accumulation of secondary metabolites in tomato fruit (Ballester et al., 2016).

Conclusions

Now that the scientific community has access to advanced tissue culture techniques, double haploidy protocols, modern phenotyping facilities, and genomic and bioinformatic tools, tomato wild relatives could be explored even more. This may provide new sources of genetic resources and R genes that could be used to pyramid new genes into one variety leading to broad and probably more durable resistance. Furthermore, ongoing advances in sequencing technology can be used to develop reference genome sequences for undiscovered tomato wild relatives, and the development of tomato pan-genomes will be a valuable strategy in harnessing the genetic diversity of these species. Additionally, genome editing enables de novo domestication strategies for the targeted use of tomato relatives (Zsögön et al., 2018). Thus, exploring the variation in tomato wild species could be an interesting topic for future studies.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author contributions

Original draft: Hamid Khazaei; review and editing: Hamid Khazaei and Adithya Madduri. All authors read and agreed to the published version of the manuscript.

Funding

Financial support was provided by the Foreign, Commonwealth and Development Office (UK) and by the long-term strategic donors to the World Vegetable Center, Taiwan: UK aid from the UK Government, the United States Agency for International Development (USAID), the Australian Centre for International Agricultural Research (ACIAR), Germany, Thailand, Philippines, Korea, and Japan. The authors thank Roland Schafleitner, Peter Hanson and Ya-ping Lin for their kind suggestions on the manuscript.

[1] Adhikari, P., Adhikari, T. B., Louws, F. J. and Panthee, D. R. (2020). Advances and challenges in bacterial spot resistance breeding in tomato (Solanum lycopersicum L.) Int. J. Mol. Sci 21, 1734. https://doi.org/10.3390/ijms21051734

[2] Anderson, T. A., Zitter, S. M., Jong, D. M. D., Francis, D. M. and Mutschler, M. A. (2021). Cryptic introgressions contribute to transgressive segregation for early blight resistance in tomato. Theor. Appl. Genet 134, 2561–2575. https://doi.org/10.1007/s00122-021-03842-x

[3] Astua-Monge, G., Minsavage, G. V., Stall, R. E., Davis, M. J., Bonas, U. and Jones, J. B. (2000). Resistance of tomato and pepper to T3 strains of Xanthomonas campestris pv. vesicatoria is specified by a plant-inducible avirulence gene. Mol. Plant-Microbe Interact 13, 911–921. https://doi.org/10.1094/MPMI.2000.13.9.911

[4] AVRDC. (1994). AVRDC 1993 Progress Report (Shanhua, Tainan, Taiwan: Asian Vegetable Research and Development Center), 201-203. https://doi.org/10.22001/wvc.66411

[5] Bailey, D. (1950). Studies in racial trends and constancy in Cladosporium fulvum Cooke. Can. J. Res 28, 535–565. https://doi.org/10.1139/cjr50c-032

[6] Bai, Y., Hulst, R. van der, Bonnema, G., Marcel, T. C., Meijer-Dekens, F., Niks, R. E. and Lindhout, P. (2005). Tomato defense to Oldium neolycopersici: dominant OI genes confer isolate-dependent resistance via a different mechanism than recessive oI-2. Mol. Plant Microbe. Interact 18(4), 354–362. doi: https://doi.org/10.1094/MPMI-18-0354

[7] Bai, Y., Kissoudis, C., Yan, Z., Visser, R. G. F. V. and Linden, G. V. D. (2018). Plant behaviour under combined stress: tomato responses to combined salinity and pathogen stress. Plant J 93, 781–793. https://doi.org/10.1111/tpj.13800

[8] Ballester, A.-R., Tikunov, Y., Molthoff, J., Grandillo, S., Viquez-Zamora, M., Vos, R. D., Maagd, R. A. D., Heusden, S. V. and Bovy, A. G. (2016). Identification of loci affecting accumulation of secondary metabolites in tomato fruit of a Solanum lycopersicum × Solanum chmielewskii introgression line population. Front Plant. Sci 7, 1428. https://doi.org/10.3389/fpls.2016.01428

[9] Beek, J. G. van der, G, P. and Lindhout, P. (1994). Resistance to powdery mildew (Oidium lycopersicum) in Lycopersicon hirsutum is controlled by an incompletely-dominant gene Ol-1 on chromosome 6. Theor. Appl. Genetics 89, 467–473. https://doi.org/10.1007/BF00225382

[10] Bohra, A., Kilian, B., Sivasankar, S., Caccamo, M., Mba, C., Mccouch, S. R. and Varshney, R. K. (2021). Reap the crop wild relatives for breeding future crops. Trends Biotech 40, 412–431. https://doi.org/10.1016/j.tibtech.2021.08.009

[11] Bolger, A., Scossa, F., Bolger, M. E., Lanz, C. and Maumuset, F. (2014). The genome of the stress-tolerant wild tomato species Solanum pennellii. Nat Genet 46, 1034–1038. https://doi.org/10.1038/ng.3046

[12] Bonde, R. and Murphy, E. F. (1952). Resistance of certain tomato varieties and crosses to late blight. Maine Agric. Exp. Stn. Bull 497, 5–15.

[13] Catanzariti, A. M., Lim, G. T. and Jones, D. A. (2015). The tomato I-3 gene: a novel gene for resistance to Fusarium wilt disease. New Phytol 207, 106–118. https://doi.org/10.1111/nph.13348

[14] Chetelat, R. T., Qin, X., Tan, M., Burkart-Waco, D., Moritama, Y., Huo, X., Wills, T. and Pertuzé, R. (2019). Introgression lines of Solanum sitiens, a wild nightshade of the Atacama Desert, in the genome of cultivated tomato. Plant J 100, 836–850. https://doi.org/10.1111/tpj.14460

[15] Chitwood-Brown, J., Vallad, G. E., Lee, T. G. and Hutton, S. F. (2021). Breeding for resistance to fusarium wilt of tomato: A Review. Genes 12, 1673. https://doi.org/10.3390/genes12111673

[16] Chunwongse, J., Doganlar, S., Crossman, C., Jiang, J. and Tanksley, S. D. (1997). High-resolution genetic map of the Lv resistance locus in tomato. Theor. Appl. Genet 95, 220–223. https://doi.org/10.1007/s001220050551

[17] Ciccarese, F., Amenduni, M., Schiavone, D. and Cirulli, M. (1998). Occurrence and inheritance of resistance to powdery mildew (Oidium lycopersici) in Lycopersicon species. Plant Pathol 47, 417–419. https://doi.org/10.1046/j.1365-3059.1998.00254.x

[18] Coaker, G. L. and Francis, D. M. (2004). Mapping, genetic effects, and epistatic interaction of two bacterial canker resistance QTLs from Lycopersicon hirsutum. Theor. Appl. Genet 108, 1047–1055. https://doi.org/10.1007/s00122-003-1531-6

[19] Crinò, P., Veroness, P., Stamigna, C., Chiaretti, D., Lai, A., Bitti, M. E. and Saccardo, F. (1995). Breeding for resistance to bacterial canker in Italian tomatoes for fresh market. Acta Hort 412, 539–545. https://doi.org/10.17660/ActaHortic.1995.412.65

[20] Darwin, S., Knapp, S. and Peralta, I. (2003). Taxonomy of tomatoes in the Galápagos Islands: Native and introduced species of Solanum section Lycopersicon (Solanaceae) System Biodivers 1, 29–53. https://doi.org/10.1017/S1477200003001026

[21] Davis, J., Yu, D., Evans, W., Gokirmak, T., Chetelat, R. T. and Stotz, H. U. (2009). Mapping of loci from Solanum lycopersicoides conferring resistance or susceptibility to Botrytis cinerea in tomato. Theor. Appl. Genet 119, 305–314. https://doi.org/10.1007/s00122-009-1039-9

[22] Dickinson, M., Jones, D. A. and Jones, J. D. G. (1993). Close linkage between the Cf-2/Cf-5 and Mi resistance loci in tomato. Mol. Plant-Microbe Interact 6, 341–347. https://doi.org/10.1094/mpmi-6-341

[23] Diwan, N., Fluhr, R., Eshed, Y., Zamir, D. and Tanksley, S. D. (1999). Mapping of Ve in tomato: a gene conferring resistance to the broad-spectrum pathogen, Verticillium dahlia race 1. Theor. Appl. Genet 98, 315–319. https://doi.org/10.1007/s001220051075

[24] Dixon, M. S., Hatzixanthis, K., Jones, D. A., Harrison, K. and Jones, J. D. G. (1998). The tomato Cf-5 disease resistance gene and six homologs show pronounced allelic variation in leucine-rich repeat copy number. Plant Cell 10, 1915–1925. https://doi.org/10.1105/tpc.10.11.1915

[25] Ebert, A. W. and Schafleitner, R. (2015). Utilization of wild relatives in the breeding of tomato and other major vegetables. In Crop Wild Relatives and Climate Change ( Redden, R, Yadav, S S, Maxted, N, Dulloo, M E, Guarino, L and Smith, P , Eds. ) (Hoboken, NJ, USA: John Wiley & Sons, Inc), 141-172. https://doi.org/10.1002/9781118854396.ch9

[26] El-Sappah, A. H., Islam, M. M., El-Awady, H. H., Yan, S., Qi, S., Liu, J., Cheng, G.-T. and Liang, Y. (2019). Tomato natural resistance genes in controlling the root-knot nematode. Genes 10, 925. https://doi.org/10.3390/genes10110925

[27] Finkers, R., Bai, Y., Berg, P. . van den, Berloo, R. V., Meijer-Dekens, F., Have, A. T., Kan, J. V., Lindhout, P. and Heusden, A. W. V. (2008). Quantitative resistance to Botrytis cinerea from Solanum neorickii. Euphytica 159, 83–92. https://doi.org/10.1007/s10681-007-9460-0

[28] Finkers, R., Berg, . P. van den, Berloo, R. V., Have, A. T., Heusden, A. W. van, Kan, J. A. van and Lindhout, P. (2007). Three QTLs for Botrytis cinerea resistance in tomato. Theor. Appl. Genet 114, 585–593. https://doi.org/10.1007/s00122-006-0458-0

[29] Finlay, K. W. (1953). Inheritance of spotted wilt resistance in tomato. II.Five genes controlling spotted wilt resistance in four tomato types. Aust. J. Biol. Sci 6, 153–163.

[30] Firdaus, S., Heusden, A. W. V., Hidayati, N., Supena, E. D. J., Mumm, R., Vos, R. C. H. D., Visser, R. G. F. and Vosman, B. (2013). Identification and QTL mapping of whitefly resistance components in Solanum galapagense. Theor. Appl. Genet 126, 1487–1501. https://doi.org/10.1007/s00122-013-2067-z

[31] Foolad, M. R., Merk, H. L., Ashrafi, H. and Kinkade, M. P. (2006). Identification of new sources of late blight resistance in tomato and mapping of a new resistance gene. In 21st Annual Tomato Disease Workshop, North Carolina State University, Fletcher, NC, USA , 4-7.

[32] Foolad, M. R. and Panthee, D. R. (2012). Marker-assisted selection in tomato breeding. Crit. Rev. Plant Sci 31, 93–123. https://doi.org/10.1080/07352689.2011.616057

[33] Forster, R. L. and Echandi, E. (1972). Relation of age of plants, temperature, and inoculum concentration to bacterial canker development in resistant and susceptible. Phytopathology 63, 773–777.

[34] Francis, D. M., Kabelka, E., Bell, J., Franchino, B., St, and Clair, D. (2001). Resistance to bacterial canker in tomato (Lycopersicon hirsutum LA407) and its progeny derived from crosses to L. esculentum. Plant Dis 85, 1171–1176. https://doi.org/10.1094/PDIS.2001.85.11.1171

[35] Gallegly, M. E. and Marvel, M. E. (1955). Inheritance of resistance to tomato race-0 of Phytophthora infestans. J. Phytopathol 45, 103–109.

[36] Ganal, M. W. and Tanksley, S. D. (1996). Recombination around the Tm2a and Mi resistance genes in different crosses of Lycopersicon peruvianum. Theor. Appl. Genet 92, 101–108. https://doi.org/10.1007/BF00222958

[37] Gao, L., Gonda, I. and Sun, H. (2019). The tomato pan-genome uncovers new genes and a rare allele regulating fruit flavor. Nat. Genet 51, 1044–1051. https://doi.org/10.1038/s41588-019-0410-2

[38] Gill, U., Scott, J. W., Shekasteband, R., Ogundiwin, E., Schuit, C., Francis, D. M., Sim, S.-C., Smith, H. and Hutton, S. F. (2019). Ty-6, a major begomovirus resistance gene on chromosome 10, is effective against tomato yellow leaf curl virus and tomato mottle virus. Theor. Appl. Genet 132, 1543–1554. https://doi.org/10.1007/s00122-019-03298-0

[39] Giordano, L. D., Avila, A. C. D., Charchar, J. M., Boiteux, L. S. and Ferraz, E. (2000). ‘Viradoro’: A tospovirus-resistant processing tomato cultivar adapted to tropical environments. Hortscience 35, 1368–1370. https://doi.org/10.21273/HORTSCI.35.7.1368

[40] Gonzalez-Cendales, Y., Catanzariti, A. M., Baker, B., Mcgrath, D. J. and Jones, D. A. (2016). Identification of I-7 expands the repertoire of genes for resistance to Fusarium wilt in tomato to three resistance gene classes. Mol. Plant. Pathol 17, 448–463. https://doi.org/10.1111/mpp.12294

[41] Gramazio, P., Pereira-Dias, L., Vilanova, S., Prohens, J., Soler, S., Esteras, J., Garmendia, A. and Díez, M. J. (2020). Morphoagronomic characterization and whole-genome resequencing of eight highly diverse wild and weedy S. pimpinellifolium and S. lycopersicum var. cerasiforme accessions used for the first interspecific tomato MAGIC population. Hort. Res 7, 174. https://doi.org/10.1038/s41438-020-00395-w

[42] Hanson, P., Green, S. and Kuo, G. (2006). Ty-2, a gene on chromosome 11 conditioning geminivirus resistance in tomato. Tomato Genet. Coop. Rep 56, 17–18. Retrieved from https://tgc.ifas.ufl.edu/vol56/html/vol56hanson.htm

[43] Hanson, P., Lu, S.-F., Wang, J.-F., Chen, W., Kenyon, L., Tan, C.-W., Tee, K. L., Wang, Y.-Y., Hsu, Y.-C., Schafleitner, R., Ledesma, D. and Yang, R.-Y. (2016). Conventional and molecular marker-assisted selection and pyramiding of genes for multiple disease resistance in tomato. Sci. Hort 201, 346–354. https://doi.org/10.1016/j.scienta.2016.02.020

[44] Have, A. t., Berloo, R. V., Lindhout, P. and Kan, J. A. L. V. (2007). Partial stem and leaf resistance against the fungal pathogen Botrytis cinerea in wild relatives of tomato. Eur. J. Plant. Pathol 117, 153–166. https://doi.org/10.1007/s10658-006-9081-9

[45] Huang, C. C., Putte, P.-H.-V.-D., Meer, J.-H.-V.-D., Meijer-Dekens, F. and Lindhout, P. (2000). Characterization and mapping of resistance to Oidium lycopersicum in two Lycopersicon hirsutum accessions: evidence for close linkage of two Ol-genes on chromosome 6 of tomato. Heredity 85, 511–520. https://doi.org/10.1046/j.1365-2540.2000.00770.x

[46] Hutton, S. F., Scott, J. W. and Schuster, D. J. (2012). Recessive resistance to tomato yellow leaf curl virus from the tomato cultivar Tyking is located in the same region as Ty-5 on chromosome 4. HortScience 47, 324–327. https://doi.org/10.21273/HORTSCI.47.3.324

[47] Ji, Y., Schuster, D. J. and Scott, J. W. (2007). Ty-3, a begomovirus resistance locus near the tomato yellow leaf curl virus resistance locus Ty-1 on chromosome 6 of tomato. Mol. Breed 20, 271–284. https://doi.org/10.1007/s11032-007-9089-7

[48] Ji, Y., Scott, J. W., Schuster, D. J. and Maxwell, D. P. (2009). Molecular mapping of Ty-4, a new tomato yellow leaf curl virus resistance locus on chromosome 3 of tomato. J. Am. Soc. Hortic. Sci 134, 281–288. https://doi.org/10.21273/JASHS.134.2.281

[49] Kanagawa Agricultural Technology Center. (1999). Online report (accessed 23 June 2022) Retrieved from http://www.pref.kanagawa.jp/docs/cf7/cnt/f70030/

[50] Leckie, B. M., D'Ambrosio, D. A., Chappell, T. M., Halitschke, R., Jong, D. M. D., Kessler, A., Kennedy, G. G. and Mutschler, M. A. (2016). Differential and synergistic functionality of acylsugars in suppressing oviposition by insect herbivores. PLoS ONE 11(4), e0153345. https://doi.org/10.1371/journal.pone.0153345

[51] Leckie, B. M., Jong, D. M. D. and Mutschler, M. A. (2012). Quantitative trait loci increasing acylsugars in tomato breeding lines and their impacts on silverleaf whiteflies. Mol. Breed 30, 1621–1634. https://doi.org/10.1007/s11032-012-9746-3

[52] Lough, R. C. (2003). Inheritance of tomato late blight resistance in Lycopersicon hirsutum LA1033. North Carolina State University thesis

[53] Ortiz, R. (2015). The importance of crop wild relatives, diversity, and genetic potential for adaptation to abiotic stress-prone environments. In Crop Wild Relatives and Climate Change ( Redden R, Yadav SS, Maxted N, Dulloo ME and Smith P , Eds. ) (Hoboken, NJ, USA: John Wiley & Sons, Inc), 80-87. https://doi.org/10.1002/9781118854396.ch5

[54] Parlevliet, J. E. (2002). Durability of resistance against fungal, bacterial and viral pathogens; present situation. Euphytica 124, 147–156. https://doi.org/10.1023/A:1015601731446

[55] Pelham, J. (1966). Resistance in tomato to tobacco mosaic virus. Euphytica 15, 258–267. https://doi.org/10.1007/BF00022331

[56] Pitblado, R. E. and Kerr, E. A. (1980). Resistance to bacterial speck (Pseudomonas tomato) in tomato. Acta Hort 100, 379–382. https://doi.org/10.17660/ActaHortic.1980.100.40

[57] Powell, A. F., Feder, A., Li, J., Schmidt, M. H. W. and Courtney, L. (2022). A Solanum lycopersicoides reference genome facilitates insights into tomato specialized metabolism and immunity. Plant J 110, 1791–1810. https://doi.org/10.1111/tpj.15770

[58] Qi, S., Zhang, S., Islam, M. M., El-Sappah, A. H., Zhang, F. and Liang, Y. (2021). Natural resources resistance to tomato spotted wilt virus (TSWV) in tomato (Solanum lycopersicum) Int. J. Mol. Sci 22, 10978. https://doi.org/10.3390/ijms222010978

[59] Rakha, M., Hanson, P. and Ramasamy, S. (2017). Identification of resistance to Bemisia tabaci Genn. in closely related wild relatives of cultivated tomato based on trichome type analysis and choice and no-choice assays. Genet. Resour. Crop. Evol 64, 247–260. https://doi.org/10.1007/s10722-015-0347-y

[60] Ramírez-Ojeda, G., Peralta, I. E., Rodríguez-Guzmán, E., Sahagún-Castellanos, J., Chávez-Servia, J. L., Medina-Hinostroza, T. C., Rijalba-Vela, J. R., Vásquez-Núñez, L. P. and Rodríguez-Pérez, J. E. (2021). Edaphoclimatic descriptors of wild tomato species (Solanum Sect. Lycopersicon) and closely related species (Solanum Sect. Juglandifolia and Sect. Lycopersicoides) in South America. Front. Genet 12, 748979. https://doi.org/10.3389/fgene.2021.748979

[61] Razali, R., Bougouffa, S., Morton, M. J. L., Lightfoot, D. J., Alam, I., Essack, M., Arold, S. T., Kamau, A. A., Schmöckel, S. M., Pailles, Y., Shahid, M., Michell, C. T., Al-Babili, S., Ho, Y. S., Tester, M., Bajic, V. B. and Negrão, S. (2018). The genome sequence of the wild tomato Solanum pimpinellifolium provides insights into salinity tolerance. Front. Plant. Sci 9, 1402. https://doi.org/10.3389/fpls.2018.01402

[62] Robbins, M. D., Darrigues, A., Sim, S. C., Masud, M. A. T. and Francis, D. M. (2009). Characterization of hypersensitive resistance to bacterial spot race T3 (Xanthomonas perforans) from tomato accession PI 128216. Phytopathology 99, 1037–1044. https://doi.org/10.1094/PHYTO-99-9-1037

[63] Roldan, M. V. G., Perilleux, C., Morin, H., Huerga-Fernandez, S., Latrasse, D. and Benhamed, M. (2017). Natural and induced loss of function mutations in SlMBP21 MADS-box gene led to jointless-2 phenotype in tomato. Sci. Rep 7, 4402. https://doi.org/10.1038/s41598-017-04556-1

[64] Roselló, S., Díez, M. J. and Nuez, F. (1998). Genetics of Tomato spotted wilt virus resistance coming from Lycopersicon peruvianum. Eur. J. Plant. Pathol 104, 499–509. https://doi.org/10.1023/A:1008622128504

[65] Rosello, S., Ricarte, B., Diez, M. J. and Nuez, F. (2001). Resistance to tomato spotted wilt virus introgressed from Lycopersicon peruvianum in line UPV 1 may be allelic to Sw-5 and can be used to enhance the resistance of hybrids cultivars. Euphytica 119, 357–367. https://doi.org/10.1023/A:1017506213974

[66] Santegoets, J., Bovio, M., Westende, W. V., Voorrips, R. E. and Vosman, B. (2021). A novel non-trichome based whitefly resistance QTL in Solanum galapagense. Euphytica 217, 43. https://doi.org/10.1007/s10681-021-02770-7

[67] Schafleitner, R., Lin, C.-Y., Khazaei, H. and Tsai, Y.-C. (2022). Manipulating fruit size in tomato by gene editing. Asian Solanaceous Round Table (ASRT-4), 11-13 May 2022. Bangalore, India.

[68] Schilmiller, A. L., Charbonneau, A. L. and Last, R. L. (2012). Identification of a BAHD acetyltransferase that produces protective acyl sugars in tomato trichomes. Proc. Natl. Acad. Sci. U.S.A 109, 16377–16382. https://doi.org/10.1073/pnas.1207906109

[69] Schmidt, M. H. W., Vogel, A., Dentonet, A. K., Istace, B. and Wormitet, A. (2017). De novo assembly of a new Solanum pennellii accession using nanopore sequencing. Plant Cell 29, 2336–2348. https://doi.org/10.1105/tpc.17.00521

[70] Scott, J. W. and Gardner, R. G. (2007). Breeding for resistance to fungal pathogens. In Genetic Improvement of Solanaceous Crops. Tomato ( M K Razdan and A K Mattoo , Eds. ) (Vol. 2), 421-456. https://doi.org/10.1201/b10744

[71] Sen, Y., Feng, Z., Vandenbroucke, H., Wolf, J. V. D., Visser, R. G. and Heusden, A. W. V. (2013). Screening for new sources of resistance to Clavibacter michiganensis subsp. michiganensis (Cmm) in tomato. Euphytica 190, 309–317. https://doi.org/10.1007/s10681-012-0802-1

[72] Sen, Y., Manrique, M. J., Kabaş, A. and Visser, R. G. (2021). Qtl Mapping of Clavibacter Michiganensis Subsp. Michiganensis (cmm) Resistance Originating from Solanum Pimpinellifolium g1.1554. PREPRINT (Version 1) . https://doi.org/10.21203/rs.3.rs-292564/v1

[73] Smith, P. G. (1944). Embryo culture of a tomato species hybrid. Proc. Am. Soc. Hort. Sci 44, 413–416.

[74] Soost, R. K. (1963). Hybrid tomato resistant to tobacco mosaic virus. J. Hered 54, 241–244. https://doi.org/10.1093/oxfordjournals.jhered.a107258

[75] Sotirova, V., Bogatsevska, N. and Stamova, L. (1994). Sources of resistance to bacterial diseases in tomato wild species. Acta Hort 376, 353–360. https://doi.org/10.17660/ActaHortic.1994.376.49

[76] Stall, R. and Walter, J. (1965). Selection and inheritance of resistance in tomato to isolates of races 1 and 2 of Fusarium wilt organism. Phytopathology 55, 1213–1215.

[77] Stam, R., Nosenko, T., Hörger, A. C., Stephan, W., Seidel, M., Kuhn, J. M. M., Haberer, G. and Tellier, A. (2019). The de novo reference genome and transcriptome assemblies of the wild tomato species Solanum chilense highlights birth and death of NLR genes between tomato species. G3 9, 3933–3941. https://doi.org/10.1534/g3.119.400529

[78] Stevens, M. and Rick, C. M. (1986). Genetics and breeding. In The Tomato Crop. A Scientific Basis for Improvement ( Atherton JG and Rudich J , Eds. ) ( Chapman & Hall), 35-109.

[79] Stevens, M. R., Scott, S. J. and Gergerich, R. C. (1994). Evaluation of seven Lycopersicon species for resistance to tomato spotted wilt virus (TVSW) Euphytica 80, 79–84. https://doi.org/10.1007/BF00039301

[80] Tanksley, S. D. and Nelson, J. C. (1996). Advanced backcross QTL analysis: a method for the simultaneous discovery and transfer of valuable QTLs from unadapted germplasm into elite breeding lines. Theor. Appl. Genet 92, 191–203. https://doi.org/10.1007/BF00223376

[81] Tourrette, E., Falque, M. and Martin, O. C. (2021). Enhancing backcross programs through increased recombination. Genet. Sel. Evol 53, 25. https://doi.org/10.1186/s12711-021-00619-0

[82] Vakalounakis, D. J., Laterrot, H., Moretti, A., Ligoxigakis, E. K. and Smardas, K. (1997). Linkage between Frl (Fusarium oxysporum f sp radicis-lycopersici resistance) and Tm-2 (tobacco mosaic virus resistance-2) loci in tomato (Lycopersicon esculentum) Ann. Appl. Biol 130, 319–323. https://doi.org/10.1111/j.1744-7348.1997.tb06835.x

[83] Vendemiatti, E., Therezan, R., Vicente, M. H., Pinto, M. D. S., Bergau, N., Yang, L., Bernardi, W. F., Alencar, S. M. D., Zsögön, A., Tissier, A., Benedito, V. A. and Peres, L. E. P. (2021). Introgression of type-IV glandular trichomes from Solanum galapagense to cultivated tomato reveals genetic complexity for the development of acylsugar-based insect resistance. bioRxiv 2021.06.18.448858. . https://doi.org/10.1101/2021.06.18.448858

[84] Verlaan, M. G., Hutton, S. F., Ibrahem, R. M., Kormelink, R., Visser, R. G., Scott, J. W., Edwards, J. D. and Bai, Y. (2013). The tomato yellow leaf curl virus resistance genes Ty-1 and Ty-3 are allelic and code for DFDGD-class RNA-dependent RNA polymerases. PLoS Genet 9 (3), e1003399. https://doi.org/10.1371/journal.pgen.1003399

[85] Vu, T. V., Das, S., Tran, M. T., Hong, J. C. and Kim, J.-Y. (2020). Precision genome engineering for the breeding of tomatoes: recent progress and future perspectives. Front. Genome Ed 2, 612137. https://doi.org/10.3389/fgeed.2020.612137

[86] Wang, J.-F., Ho, F.-I., Truong, H. T. H., Huang, S.-M., Balatero, C. H., Dittapongpitch, V. and Hidayati, N. (2013). Identification of major QTLs associated with stable resistance of tomato cultivar ‘Hawaii 7996’ to Ralstonia solanacearum. Euphytica 190, 241–252. https://doi.org/10.1007/s10681-012-0830-x

[87] Wang, X., Gao, L., Jia, C., Stravoravdis, S. and Hosmani, P. S. (2020). Genome of Solanum pimpinellifolium provides insights into structural variants during tomato breeding. Nat. Commun 11, 5817. https://doi.org/10.1038/s41467-020-19682-0

[88] Yan, Z., Pérez-De-Castro, A., Díez, M. J., Hutton, S. F., Visser, R. G. F., Wolters, A.-M.-A., Bai, Y. and Li, J. (2018). Resistance to tomato yellow leaf curl virus in tomato germplasm. Front. Plant Sci 9, 1198. https://doi.org/10.3389/fpls.2018.01198

[89] Yordanov, M., Stamova, L. and Stoyanova, Z. (1975). Leveillula taurica resistance in the tomato. TGC Rep 25, 24.

[90] Yu, Z. H., Wang, J. F., Stall, R. E. and Vallejos, C. E. (1995). Genomic localization of tomato genes that control a hypersensitive reaction to Xanthomonas-campestris pv. vesicatoria (Doidge) dye. Genetics 141, 675–682. https://doi.org/10.1093/genetics/141.2.675

[91] Zamir, D., Ekstein-Michelson, I., Zakay, Y., Navot, N., Zeidan, M., Sarfatti, M., Eshed, Y., Harel, E., Pleban, T., Van-Oss, H., Kedar, N., Rabinowitch, H. D. and Czosnek, H. (1994). Mapping and introgression of a tomato yellow leaf curl virus tolerance gene, TY-1. Theor. Appl. Genet 88, 141–146. https://doi.org/10.1007/BF00225889

[92] Zhu, M., Jiang, L., Bai, B., Zhao, W., Chen, X., Li, J., Liu, Y., Chen, Z., Wang, B., Wang, C., Wu, Q., Shen, Q., Dinesh-Kumar, S. P. and Tao, X. (2017). The intracellular immune receptor sw-5b confers broad-spectrum resistance to tospoviruses through recognition of a conserved 21-amino acid viral effector epitope. Plant Cell 29, 2214–2232. https://doi.org/10.1105/tpc.17.00180

[93] Zsögön, A., Čermák, T., Naves, E., Notini, M. M., Edel, K. H., Weinl, S., Freschi, L., Voytas, D. F., Kudla, J. and Peres, L. E. P. (2018). De novo domestication of wild tomato using genome editing. Nat. Biotechnol 36, 1211–1216. https://doi.org/10.1038/nbt.4272