Gabriel Alonso de Herrera (Talavera de la Reina, Toledo, 1470–1539) wrote his Agricultura general (General Agriculture) at the request of Cardinal Cisneros [1]. First published in Alcalá de Henares in 1530 by the Imprenta de Brocar, the work went through several editions and was translated into Latin, Italian and French. Spanning 230 pages, it is dedicated to viticulture and describes the main characteristics of several varieties cultivated in Castile in the 15th century that are still grown today, including Torrontés, Moscatel, Cigüente, Jaén and Hebén. Hebén is described as a white grape variety producing large, sparse bunches of grapes with large seeds. Possibly originating in North Africa, the Hebén variety is female and, through crosses with other varieties between the 9th and 12th centuries, has produced many descendants, representing the genetic contribution of the Iberian Peninsula to modern Vitis cultivars [2–4].

In The Gardeners’ Dictionary (1752) [5], Philip Miller (1691–1771) mentions several varieties of Vitis, in addition to V. sylvestris Labrusca, including V. praecox columellae, V. corinthiaca, V. laciniatis foliis and V. subhirsuta. Some of these varieties correspond to actual cultivars; for example, V. uva perampla corresponds to Chasselas Blanc, a cultivar of unknown origin [6] that gives the wines of Valais in Switzerland.

The Royal Botanical Garden of Madrid conserves the ampelographic material (leaves and shoots) collected and preserved by Simón de Rojas Clemente y Rubio (Titaguas, Valencia, 1777-Madrid, 1827), the author of Variedades de la vid común que vegetan en Andalucía (Varieties of the common vine that grow in Andalusia) [7]. His herbarium, the oldest vine herbarium in existence, is still used for studies of phenotypic and genetic diversity, molecular characterisation and wine history, providing a unique insight into vine cultivation in the early 19th century (the pre-phylloxera era). Due to his herbarium and writings, which were translated into French, Simón de Rojas Clemente is often regarded as the father of modern ampelography.

Modern clonal selection began around 1876. The first registered “grapevine clone” was of V. vinifera cv. Silvaner variety [8]. Hermann Müller (1850–1927), who worked at the Geisenheim Grape Breeding Institute, created the Müller-Thurgau grape variety (a cross between Riesling and Madeleine Royale) and reported the inheritance of traits such as early ripening and yield using phenotypic selection [9].

The Grapes of New York (Hedrick, 1870–1951; [10]) describes the ampelographic characteristics of Vitis cultivars and species, and in the article entitled A Century of American Viticulture, Read and Gu [11] outlined the key topics covered in articles published over the course of a century in the journal Proc. Amer. Soc. Hort. Sci., including chromosome counts, self-fertility, parthenocarpy and seed abortion, fruiting habit, and disease resistance. Preliminary breeding results were reported, and examples of trait inheritance, including sex determination, fruit colors, resistance to pathogens, and dioecy and dimorphism, were given [12–21]. For centuries, the main objectives of viticulture have been related with adaptation to changing environmental conditions, including biotic (salinity, temperature, drought, …), and abiotic (pests and pathogens) factors, as well as the optimization of biochemical characters (quality) and yield (Fig. 1). This review summarises how recent developments can affect our understanding of, and improvements to, these aspects. Optimising viticultural possibilities requires knowledge of the genetic composition of Vitis species and cultivars. While some varieties are reported to be direct selections from wild types (e.g., Traminer, [22,23]), others are known to be crosses between existing cultivated varieties (e.g., Cabernet Sauvignon, which is a cross between Sauvignon Blanc and Cabernet Franc, [24]). Crosses between wild types and varieties also exist: Riesling, for example, is a cross between Gouais and a Traminer × V. silvestris hybrid [22,25,26]. Similar to Hebén in Spain and Heunisch in Germany, Gouais is the parent of dozens of cultivars [6].

Classical genetic maps were based on phenotypic markers. The inheritance of traits was observed in the progeny (F1, F2 or backcross generations) and linkage was estimated by calculating the frequencies of recombination between traits. To include genes in maps, the traits had to follow a Mendelian pattern and be controlled by single genes with clear dominant/recessive characteristics. This classical analysis, which was based on phenotypic observations, controlled crosses and Mendelian principles, was first developed in Drosophila [27] and worked well in other small organisms with rapid life cycles, such as Arabidopsis [28]. However, this approach encountered difficulties in Vitis, an organism with a long generation time, high heterozygosity and a complex genome comprising 19 chromosomes (2n = 38). These characteristics made linkage analysis of observable traits challenging. Thanks to the development of the Polymerase Chain Reaction (PCR) and the application of molecular markers, the prospect changed at the end of the 20th century. Usage of Microsatellites [29] and other PCR-based markers, such as amplified fragment length polymorphism (AFLPs) [30], greatly reduced the time required to create genetic linkage maps. These DNA markers are useful for germplasm characterisation, marker-assisted selection, marker-assisted introgression and genomic selection. Vezzulli et al. and Tympakianakis et al. [31,32] review genetic markers and the development of genetic maps in grapes.

Lodhi et al. [33] used a two-way pseudo testcross between Cayuga White and Aurora to cover 1176 and 1477 cM, respectively, using 422 RAPD markers and 16 AFLP and isozyme markers. Further research by different groups expanded the range of available markers. Findings on co-dominant microsatellite-based markers provided good coverage of the Vitis genome. Doligez et al. mapped 1002 cM using 250 AFLP and 44 SSR markers [34], while Grando et al. developed 1639 cM using 338 AFLP microsatellite markers for the wine cultivar Moscato Bianco (Vitis vinifera L.), defining the 19 linkage groups of the Vitis riparia Michx. paternal map with 429 loci covering 1518 cM [35]. Doligez et al. used Carthagene to map 1647 cM Kosambi with 502 SSRs and 13 other types of PCR-based markers in Vitis vinifera L. [34]. Recognition of the importance of these maps came with the establishment of the Vitis Microsatellite Consortium (VMC) to develop a map based on a set of 371 microsatellite (SSR) markers [36,37]. Maps in Vitis rupestris and Vitis arizonica were developed to identify the loci responsible for the resistance to infections caused by the nematode Xiphinema index and the bacterium Xylella fastidiosa [38].

Wang et al. reviewed the advances in the field of Vitis genomics and its applications [39]. The first two Vitis genomes were published in 2007: one was a Pinot Noir clone (ENTAV115), which is grown in various soils for producing red and sparkling wines and is not self-pollinating [40]; the other was a highly homozygous V. vinifera genotype (PN40024) [41]. The PN40024 originated from the Helfensteiner genotype, resulting from a cross between Pinot Noir and Schiava Grossa in 1931. It was then bred to almost full homozygosity through successive self-pollinations [42]. A 474 Mb sequence revealed evidence of an ancient hexaploidization event and contained a set of 30,434 protein-coding genes across 19 chromosomes, with an average of 372 codons and five exons per gene. This number was significantly lower than the one observed in poplar (Populus trichocarpa Torr. & A.Gray ex Hook.), which has a similar genome size of 485 Mb, or rice (Oryza sativa L.), with a smaller genome size of 389 Mb [43,44]. However, Vitis showed a number of 3000 protein-coding genes more than the reported for Arabidopsis thaliana, despite its genome size being 3.5 times smaller at 135 Mb [45]. A summary of advances in Vitis genomics is shown in Table 1.

Different approaches revealed an average of 41.4% repetitive DNA/transposable elements in the grapevine genome. This is a slightly higher proportion than that identified in the rice genome (33%–38%). New genomic sequences of PN40024 demonstrated that this cultivar resulted from nine selfings of cv. ‘Helfensteiner’ (a cross between ‘Pinot noir’ and ‘Schiava grossa’), rather than a single ‘Pinot noir’ cultivar. This data led to an improved version of the reference sequence called PN40024.v4 [42]. Updates to the genome include rootstocks from crosses between V. vinifera, V. riparia, V. rupestris, and V. berlandieri, as well as alternative spliced isoforms [68]. A gap-free, telomere-to-telomere reference genome for the PN40024 cultivar was published in 2023 [66]. This genome is 69 Mb longer than previous versions and contains 67% repetitive sequences, 19 centromeres, 36 telomeres, and 9018 additional genes. A summary of the published grape genomes consists of 16 for V. vinifera subsp. vinifera, 21 for wild Vitis species and nine for interspecific hybrids [39].

Additional data from the Amur grape (Vitis amurensis Rupr.), V. riparia and V. labrusca [53,57,63] as well as from cultivars such as Chardonnay, Shiraz, Shine and Muscat [50,60,64] has improved our understanding of plant-pathogen interactions, cold resistance and the influence of domestication on sex determination as well as the metabolism of phenols. For example, salt-tolerant loci were identified using a pangenomic-GWAS approach based on methods of pairwise whole-genome alignment [61]. Studies on the genomics of berry related traits and other quality aspects involve those of Guo et al. [61] and others.

The genomes of modern cultivars are insufficient for investigating changes during domestication. To this end, the genome of Vitis vinifera subsp. sylvestris has been analysed in several studies [51,69,70]. Contrasting results from these studies led to a new project involving the analysis of 3186 new sequences [3]. This work provides new insights into the origins and relationships between Vitis sylvestris and cultivars, supporting the theory of a dual origin of V. vinifera. The study defines six groups of pure or nearly pure ancestries among cultivated vines: Western Asian table grapevines (CG1); Caucasian wine grapevines (CG2); muscat grapevines (CG3); Balkan wine grapevines (CG4); Iberian wine grapevines (CG5); and Western European wine grapevines (CG6), and describes selective sweep genes in 132 regions for CG1 and 887 genes in 137 regions for CG2. CG5 is well represented by Hebén, a female cultivar that is the progenitor of many other cultivars in Spain and Portugal [2–4].

Traditional genomic sequences are linear representations of an organism’s DNA, usually assembled as a reference genome from a consensus of multiple individuals or sequencing reads. In diploid organisms, the two homologous chromosomes—each inherited from one parent—are typically collapsed into a single composite sequence. While this simplification facilitates general analyses, it masks the physical linkage of variants and fails to capture how alleles are inherited together. In contrast, haplotype-resolved sequences provide a more accurate picture by distinguishing between the two chromosome copies, enabling the identification of how specific alleles are linked across loci. This approach is particularly important for studying highly heterozygous species and genomic regions with reduced recombination. Haplotype research identifies genetic variations within populations that can be linked to functional traits like cold tolerance, berry size, or sugar composition.

In clonally propagated plants such as grapevine (Fig. 2), somatic mutations accumulate over time, further increasing intra-varietal diversity. Studies have shown transposable elements significant contribution to somatic polymorphism in Vitis [71], and such mutations occur more frequently in intergenic regions than in coding sequences [55]. As a result, different clonal lines of the same cultivar can carry varying levels of heterozygous structural variants (SVs). Many horticultural species, including Vitis, are outbreeding and consequently exhibit high levels of heterozygosity. For instance, SNP-level heterozygosity has been estimated at 1.02% in pear (Pyrus communis L.) [72] and 2.27% in lychee (Litchi chinensis) [73], while in Vitis, it ranges from as low as 0.01% in the inbred PN40024 line to 0.20%–0.40% in more diverse genotypes [74]. These high levels of heterozygosity and structural variation complicate genome assembly and gene mapping, requiring haplotype-resolved diploid genomes for precise allele identification and QTL analysis. Thanks to recent advances in long-read sequencing and assembly technologies [75,76], fully phased diploid genomes have been generated in multiple species [77], including several Vitis cultivars [50,52,70,75,78–80].

Reproductive strategies in Vitis play a crucial role in shaping genome structure. While wild Vitis species are typically dioecious and outcrossing, domesticated grapes have predominantly vegetative propagation, with occasional hybridization events. Each reproduction mode—outcrossing, selfing, or clonal propagation—has distinct genomic consequences. Clonal propagation leads to the accumulation of somatic mutations and increased heterozygosity [74]; in contrast, self-fertilization reduces heterozygosity, purging deleterious alleles and increasing homozygosity. Cross-breeding and clonal propagation, on the other hand, tend to mask such mutations. To understand the genomic consequences of these reproductive modes, researchers compared a haplotype-resolved genome of PN40024 with two haplotypes (PN1 and PN2) derived from a different Pinot Noir clone. This comparison revealed extensive haplotypic diversity, including unique gene families and structural variations [74]. Resequencing data from 38 Vitis vinifera samples—comprising 18 PN clones, 20 wild grapevines, and 3 muscadine grapes as outgroups—further enabled the detection of selection signatures in PN clones, particularly in chromosomes 1, 3, 4, 5, and 18, and introgression signals from European populations in chromosomes 1, 2, 3, and 19.

Admixture analysis clarified the genetic relationships among clones. PN40024 clones showed genetic independence compared to other genotypes such as HE (Helfensteiner), GB (Gouais Blanc), and CD (Chardonnay), which retained mixed genotypes from their parentals. For example, HE derives from PN and SG (Schiava Grossa), while CD and GN (Gamay Noir) originate from crosses between PN and GB. Among these, the PN40024 clones exhibited the lowest levels of nucleotide diversity and heterozygosity, consistent with the effects of prolonged self-fertilization. To further explore how recombination affects genetic load, researchers used SIFT (Sorting Intolerant From Tolerant) to identify deleterious SNPs (dSNPs). Clonal groups (PN, SG, GB, CD, GN, HE) exhibited a significant higher genetic burden than wild outcrossing groups from Europe (EU) and the Middle East (ME). Notably, selfed PN40024 carried the highest recessive burden and the lowest heterozygous burden. Across 167 examined combinations, the genotypes were often heterozygous in PN, SG, or HE, but homozygous in PN40024, illustrating how selfing unmasks deleterious variants. Interestingly, in the GB sub-lineage—including GB, CD, and GN—many mutations remained in a heterozygous state due to close linkage of deleterious and structural variants in repulsion, which can maintain heterozygosity even after successive selfings [74].

Overall, these findings underscore how breeding practices and reproductive modes in grapevine—whether clonal propagation, selfing, or crossing—profoundly shape genome heterozygosity, structural variation, and the accumulation of deleterious mutations. Haplotype-resolved genomic analysis emerges as an indispensable tool for unraveling these complex patterns in grapevine evolution and improvement.

Dioecy, the condition in which male and female reproductive structures are found on separate individuals, is relatively rare, affecting only about 6%–8% of angiosperms. It is often associated with traits such as monoecy, wind pollination, and climbing growth [81], and occurs in a number of agronomically important species, including Carica papaya L., Actinidia chinensis Planch., Fragaria vesca L. [82–84], and various species of Silene and Rumex [85–89]. Within the Vitaceae family, dioecy is observed in Vitis and Tetrastigma, and has been the focus of comparative studies across these genera [90]. During grapevine domestication, a significant reproductive shift occurred—from dioecy to hermaphroditism—enabling self-pollination and increased breeding control.

Early genetic models attempted to explain this transition. Oberle [91] proposed a two-gene system, with dominant alleles So and Sp controlling ovule suppression and pollen development, respectively; males were heterozygous at both loci, while females were homozygous recessive. Recombination between these genes could yield hermaphrodites. Levadoux [92] later suggested a single locus with three alleles (M > H > F) controlling the development of male, hermaphrodite, and female flowers. These hypotheses laid the groundwork for later studies that mapped sex determination to a ~150-kb region on chromosome 2, now known as the Sex Determining Region (SDR) [93,94].

Detailed molecular analysis of the SDR has uncovered a suite of candidate genes implicated in floral sex determination. Fechter et al. [93] identified genes involved in cytokinin metabolism (e.g., a flavin-containing monooxygenase and an adenine phosphoribosyltransferase) as well as markers capable of distinguishing between male, female, and hermaphrodite plants. Experimental work supported these roles; for instance, Negi and Olmo [95] demonstrated that exogenous application of cytokinins could induce hermaphroditic flowers from male plants. Additional candidate genes—such as trehalose-6-phosphate phosphatase (TPP), WRKY transcription factors, and ETO1, involved in ethylene metabolism—have also been proposed [56,96].

This ~400-kb SDR, extending from 4.90 to 5.33 Mb on chromosome 2, marks a region of strong divergence between wild and cultivated grapevines [97]. Allele frequency analyses revealed two peaks of divergence, with 13 and 32 genes, respectively. In one peak, six genes were significantly overexpressed in female (F) versus male (M) and hermaphrodite (H) flowers, including VviFSEX, a candidate male sterility gene. Male individuals are typically heterozygous (M/f), females homozygous recessive (f/f), and recombination in this region is nearly absent, preserving sex haplotypes. Genome-wide resequencing of 556 accessions from Europe, East Asia, and North America confirmed that the SDR and its boundaries are conserved across the Vitis genus [97]. Strong linkage disequilibrium is observed in wild species, while recombination patterns along the H haplotypes of cultivated accessions revealed two distinct forms: H1 and H2.

Subsequent studies have narrowed the genetic elements of the SDR. Coito et al. [98] identified VviAPRT3 as a key gene associated with male fertility and found ten genes carrying female-specific SNPs, including INAPERTURATE POLLEN 1 (INP1), a strong candidate for male promotion. Badouin et al. [99] compared SDR haplotypes (X, Y, Yh) between wild and cultivated Vitis, revealing that the Yh haplotype derives from Y, and carries more transposable elements. They further identified a conserved 93-kb segment essential for the male phenotype, present as either XYh or YhYh in the 5^′ part of the locus, and never as YhYh in the 3^′ end. Among 13 cultivars examined, six showed recombinant haplotypes, suggesting structural rearrangements within the SDR are common. Massonnet et al. [56], analyzing twenty haplotypes, confirmed sex-linked regions, identified a candidate male sterility mutation in VviINP1, and proposed that VviYABBY3 may underlie female sterility. Their findings support the hypothesis that domesticated grapevines became hermaphroditic due to a rare recombination between male and female SDR haplotypes.

Finally, recent transcriptomic data add another layer of complexity. Nunhes-Ramos et al. [100] analyzed three developmental stages across all three flower types in Vitis, uncovering transcriptional activity in intergenic and unannotated regions, hinting at the presence of novel sex-related genes. These findings suggest that even after extensive mapping, important components of the SDR may remain unidentified.

Together, these genetic, genomic, and transcriptomic studies provide a comprehensive picture of how sex determination in Vitis is controlled and how its evolution during domestication led to the stable hermaphroditism observed in modern cultivars. The SDR stands as a key locus of both fundamental biological interest and practical relevance in grapevine breeding.

Epigenetic modifications—such as DNA methylation, histone modifications, and chromatin remodeling—play essential roles in regulating gene expression without altering the underlying DNA sequence. These modifications are modulated by environmental conditions and the changes are inherited. In plants, DNA methylation in promoters typically represses gene activity, whereas gene body methylation may influence processes like alternative splicing [101]. In grapevine (Vitis vinifera), these mechanisms are crucial for development, stress responses, and environmental adaptation, particularly in the context of vegetative propagation [102,103].

Domesticated grapevines exhibit higher levels of DNA methylation compared to wild relatives, especially at genes related to stress responses, hormone signaling, and secondary metabolism [104]. Methylation divergence has been associated with selection during domestication and adaptation to clonal propagation. Vineyard populations show terroir-driven epigenetic structuring, with methylation patterns clustering geographically even when genetic diversity is low [103]. Moreover, somatic stress memory may persist over seasons: Tan et al. [105] found that drought/heat-primed vines retained altered DNA methylation and stronger transcriptional responses to stress even a year after priming, suggesting long-term epigenetic memory in perennials. Histone modifications offer additional regulatory complexity. Wang et al. [106] identified 117 histone-modifying genes in grapevine, with functions in seed development, powdery mildew resistance, and hormonal responses. Zuo et al. [107] identified three H3K27 methyltransferase genes—VvH3K27-1/2/3—which were downregulated during berry development and repressed under H₂O₂ treatment, linking histone methylation to ripening control. Similarly, Zhu et al. [108] showed dynamic H3K27me3 redistribution in response to cold stress, suggesting transient chromatin regulation under abiotic stress. The application of iron oxide nanoparticles has also been linked to changes in antioxidant profiles and gene expression patterns related to stress responses, potentially involving epigenetic mechanisms [109].

Postharvest quality and metabolic stability in grape berries can be significantly altered by organic treatments and nutrient supplementation, with evidence pointing to underlying epigenetic regulation of phenolic biosynthesis. Recent studies have highlighted the relevance of epigenetic regulation postharvest. Jia et al. [110] demonstrated that treatment with 5-azacytidine (a DNA demethylating agent) and trichostatin A (a histone deacetylase inhibitor) altered sugar, acid, and aroma profiles in ‘Shine Muscat’ berries. Notably, VvHDA15 emerged as a key histone deacetylase regulating postharvest quality traits, connecting acetylation to VOC composition and flavour. At the proteomic level, Pei et al. [111] mapped 822 lysine methylation sites in ripening berries, implicating epigenetic marks in energy metabolism and fruit quality. Similarly, Battilana et al. [112] found histone mark differences at the VvOMT3 locus between skin and flesh tissues, showing epigenetic control of methoxypyrazine production. Methoxypyrazines are chemical compounds in wine that produce herbaceous or vegetal aromas and they are particularly prominent in grape varieties such as Sauvignon Blanc and Cabernet Sauvignon.

Plant-pathogen interaction represents the third major focus for epigenetic analysis. Pereira et al. [113] reviewed the multifaceted epigenetic landscape in grapevine–pathogen interactions, underscoring the importance of chromatin remodeling and small RNAs in defence priming.

Altogether, the expanding field of grapevine epigenetics points to a multilayered regulatory network that modulates traits from development to postharvest quality [114]. These mechanisms provide a promising frontier for biotechnology and breeding aimed at improving grapevine resilience, yield, and wine quality under global climate challenges.