In recent years, molecular studies have proved that interspecific hybridisation and introgression are central processes in the evolution of Vitis genus ^[6]. Introgression is considered a process mediated by the transfer of genes through repeated backcrosses and when occurring from crops to its wild relatives can have deleterious consequences on the genetic structure and conservation of populations. On the other hand, the inverse process of introgression from wild to crop may be considered a rapid method for the crop to adapt to new environments. The admixture between perennial crops and wild progenitors has hardly been studied and genetic analysis was not always able to trace the gene flow, especially if an elevated number of generations have elapsed. Recent molecular studies have shown that the role of introgression appears to have been fundamental in grapevine [13,14,15]. Today, little is known about the effect of introgression, but the continuing extinction of sylvestris plants with a significant reduction in gene diversity and heterozygosity of populations in respect to vinifera, is causing a serious demographic decline of wild grapevine. An increasing number of studies have proposed that the maintenance and the conservation of wild populations should be a primary aim in Europe because these plants are a unique and fundamental genetic resource for the improvement of the cultivated grapevine in the future [16,17]. Some molecular studies have been proposed recently with the aim of studying genomic divergence between the two subspecies, but greater efforts should be made to explore the real level of introgression. Moreover, some urgent issues which are still pending should be examined such as the effective direction and intensity of gene flow between wild and domesticated forms as well as the accurate estimation of admixture times. Future works should be directed to identify which genomic regions are involved in gene flow. For example, signals of introgression might not be diffused in the entire genome but localised in specific chromosomes.

A limit of the research aimed to investigate the origin of grapevine domestication is, undoubtedly, the interpretation of the past through the study of modern cultivars. An important contribution in dealing with this issue comes from archaeological remains. So far, the most common method used to study the diversity of archaeological pips has been based on morphometric analysis. Wild and domesticated grapevine seeds can be distinguished based on seed shape, contributing greatly to connecting past to present diversity. Basically, sylvestris seeds are spherical with a small beak, while the vinifera seeds are pyriform-shaped with a well-developed beak. Thanks to morphological analysis of archaeological seeds, new insight on secondary domestication centre has been suggested, such as a domestication centres in the Languedoc region in France ^[7], and an early local grapevine domestication in prehistoric Greece ^[8]. The combination of seed morphological and genetic characterisation should allow a better understanding of the grapevine domestication process. Nevertheless, if the genetic characterisation of modern varieties had a great impact among researchers with very successful results, the same could not be said about the study of ancient DNA (aDNA). The first results on genetic diversity of grapevine aDNA were not completely satisfactory  for several reasons. First, aDNA from archaeobotanical specimens must be correctly preserved and only charring and waterlogging samples are a good source for DNA amplification. Secondly, aDNA should not be contaminated by exogenous DNA. Thirdly, a high amount of template DNA is needed. The next-generation sequencing techniques provide a significant boost to aDNA studies. Indeed, short read length makes this new technology ideal for aDNA research, guaranteeing reliable results. Wales et al. ^[9], for the first time, have high-throughput sequenced aDNA from archaeological grape specimens coming from Armenia, England, Israel, Italy and Turkey, dating ca. 4000 BCE–1500 CE. 

Moreover, all genetic variations, that ranging from SNPs to large genomic structural variants (SVs) such as duplications, inversions and transpositions, are the result of selection through time. The origin of SVs in plants is relatively poorly understood as are the mechanisms that govern the gene gain and loss, even though many important agronomic traits may be determined by these changes [21]. Due to domestication, the grapevine has experienced a bottleneck and vegetative reproduction led to the accumulation of recessive deleterious mutations. On the other hand, the stability of phenotype has made the clonal propagation attractive in agriculture. Grapevine is an ideal candidate to study genetic variations in clonal systems and, over the last few years, many resequencing studies focus on the effects of SVs throughout domestication. Zhou et al. ^[10] showed that domesticated grapevine, compared with its wild dioecious progenitor, has accumulated SVs and suggest that these modifications are a major driving force in the domestication process. In the future, comprehensive evolutionary studies need to resequence an extensive number of genomes including wild relatives of crops. Unfortunately, a part of genetic diversity included in the wild grapevine lineages may be lost due to climate changes that occurred in the past or the anthropogenic pressures in the recent times. Accessions which originate from different geographical regions or that show different phenotypes, should be collected to maximise the diversity. Moreover, to acquire full knowledge of genetic diversity and to gain full understanding of genomic variations, the pan-genome of grapes should be planned. Generally, the pan-genome refers to a full complement of genes of a species, but in grapes the concept could be expanded to the clade that includes the wild species of Vitis genus. Recent studies propose to produce a super-pan-genome for each crop, using at least one de novo assembly from each species. In this way, it is possible to reduce the bias that could be produced mapping the sequencing data from genetically distant species. The Vitis genus counts around 60–70 taxa widespread throughout Eurasia and Northern America and several of them are inter-fertile. Wild grapes are adapted to a wide range of climatic conditions and harbour genes resistant or tolerant towards both biotic and abiotic stresses, and several taxa are used today, as in the past, to produce rootstocks resistant to pathogens and pests, to drought and salinity, as well as cultivars characterised by a good quality of fruit and suitable for winemaking. Thus, the genetic material conserved in wild grapes is a source of resistance to several stresses useful to improve the cultivars by traditional agronomic strategies or modern genomic editing methodologies.

Over the last two decades, an increasing number of studies aimed to examine the genetic resources of grapevine and to investigate its ancestries. Several studies proposed that the main domestication occurred in the Southern regions of Caucasus, but recent insight suggests that a primo-domestication centre could be extended to Central Asian countries. In these areas, the grapevine has suffered from a history of protracted cultivation, thus, the pre-domestication phase may have begun earlier than previously thought. Even if these results fit well with the protracted model of crop domestication, successive studies are needed to define the times of transition between different domestication phases. Grapevine cultivars were introduced to the Mediterranean basin only successively, but secondary centres of domestication and diversification are also highly debated. Several years of breeding seem to have obfuscated the signatures of the secondary domestication processes and recent molecular studies have shown that the role of introgression appears to be fundamental. Introgression from sylvestris to vinifera aided by human activity have contributed to the domestication processes. Wild populations have had enough time to adapt to local environments and they harbour desirable traits useful for the improvement of the varieties. On the other hand, gene flow from vinifera to sylvestirs has been widely detected and it can have a significant impact on the conservation of wild populations. On the basis of data reported, the introgression is far from uncommon, thus, we propose that a detailed screening of gene flow which occurred between sylvestris and vinifera germplasms should be conducted urgently. Today the grapevine domestication process is a challenge which is far from being completely solved and some issues remain pending. We argue that the realisation of a pan-genome of grapes could be a useful resource to track the change of genes which have occurred during different phases of domestication. In the future, whole-genome resequencing analysis will make it possible to explore a large portion of the variabilities in grapevine and some of the above mentioned pending issues are expected to be solved. However, we are also aware that only by increasing the sampling of landraces and wild populations distributed in remote regions and particularly in Central Asian countries, will it be possible to increase the chance to obtain a complete picture of genetic relationships and go back to the roots of the domestication process.