1. Introduction

Capsicum is an economic crop cultivated worldwide for spice in a wide array of cuisines, ornamental plants, source of vitamins, minerals, bioactive compounds, biopesticides, components of cosmetics, and other indigenous, medicinal, and industrial uses. The popularity of Capsicum caught the attention of breeders, researchers, and enthusiasts to propagate and develop this wonder crop. The number of Capsicum cultivars and taxonomic varieties is increasing [1, 2]; however, the genus Capsicum has five domesticated species and around 25 identified species [3]. These five Capsicum taxa (C. annum, C. baccatum, C. chinense, C frutescens, and C. pubescens) can be differentiated through their morphological characteristics like bloom and seed color, calyx form, number of flowers per node, and flower orientation [1, 3, 4]. Interestingly, C. annum is considered to have been domesticated from C. annum populations in the wild, while Annum glabriusculum in Mexico was derived from many geographically distinct wild populations [3].

2. Capsicum biology and horticultural characteristics

The CABI Compendium features Capsicum’s biology and horticultural characteristics as follows [5]. Capsicum grows to a height of 0.5–1.5 m, is heavily branched, and has extremely strong taproots. The lateral roots are many, while the stem is uneven and angular, measuring around 1 cm in diameter and measuring about 0.5–1.5 m in length. The stem is normally green to brown-green in color, with purple patches near the node on occasion. The leaf design is alternate, basic, and highly changeable, with petioles up to 10 cm long. The apex is acuminate, and the edge is whole, pale dark green, and subglabrous. The flowers are arranged singly, and the pedicel is around 4 cm long when in bloom. The fruits may grow up to 8 cm in length. The calyx is cup-shaped and with enlarged fruit. Generally, it has five conspicuous teeth, and the white corolla has five to seven lobes. It can develop to five to seven stamens with pale blue to purplish anthers. The ovary is 2–4 locular, style filiform, and has a white or purplish stigma capitate. Fruit is a non-pulpy berry variable in size, shape, color, and degree of pungency [5]. Fruits are relatively conical with up to 30 cm long. The colors tend to be green, yellow, cream, or purplish when it is not yet fully developed. However, it becomes red, orange, yellow, or brown when it matures. The seeds are orbicular and flattened, about 3–4.5 mm in diameter, 1 mm thick, and pale yellow in color. The plant is considered an annual, herbaceous, perennial, seed propagated, shrub, and climber.

Domesticated crop seeds germinate 6–21 days after seeding, with continuous blooming beginning 60–90 days later. The flower is open for 2–3 days, and outcrossing of up to 91% may occur, depending on bee activity and heterostyly, although it is typically considered a self-pollinated crop. Approximately 40–50% of the flowering set fruit matures 4–5 weeks after blooming and can be plucked in 5–7 days intervals under typical conditions. The harvest time is around 4–7 months following the seeding stage [5].

The untamed seed dormancy in wild C. annum seeds is staggered, allowing germination and recruitment to occur when conditions are best in a more unpredictable and uncertain environment [6]. Wild seeds’ testae are thicker than domesticated plants, generating more but smaller seeds, which are better equipped for dispersion [6]. Insect pollinators outcrossed C. annum in the wild at a significant rate were noted [6]. Flowering occurs late in the season, but once it does, it is persistent and prolific, with overlapping stages of flower and fruit development [6]. Capsicum plants may grow as permanent shrubs in a suitable climate, although they are commonly grown as annuals elsewhere [6]. Light, well-manured, limey, and well-drained soil is preferred [1].

Capsicum peppers are day-neutral, warm-season plants; however, certain varieties may exhibit a photoperiodic reactivity [5]. The vegetative cycle may be accelerated by enforcing particular photoperiods [5]. Capsicum peppers can withstand 45% of prevailing sun energy in a shaded environment [5], although shadow might delay flowering.

Capsicum peppers thrive in loam soil with a pH of 5.5–6.8 [5]. They grow at various elevations, with rainfall ranging from 600 to 1250 mm [5]. Cultivars are destroyed by severe floods or drought [5]. The optimum germination temperatures are between 25 and 30°C and can withstand temperatures as low as 15°C at night [5]. The plant can yield fruit, albeit it will be delayed if the temperature drops below 25°C [5]. If the night temperature hits 30°C, flower buds will abort rather than mature [5]. When the temperature reaches 30°C, and below 15°C, the pollen viability is significantly reduced [5].

Capsicum seeds are dispersed in various ways. C. annum is transmitted via the movement of seeds, which are generated in vast quantities and can endure for more than a year [3]. Chilies are the favorite food of many birds in their natural range; they drop seeds while eating the fruits or pass through the digestive tract unharmed [3]. Humans also intentionally spread the species to use its fruits and leaves as food, spice, ornamental, and medicine [1, 7]. It is believed to have escaped cultivation accidentally in Puerto Rico and Finland [8, 9]. Because the species can grow in sandy, coastal environments, it can be spread by both biotic and abiotic vectors [10].

3. Ploidy levels and chromosome structure

Studies of ploidy levels and chromosome structure of Capsicum provide essential data for Capsicum taxonomy, assisting in the identification of cultivated, semi-cultivated, and wild species, as well as contributing to plant variety improvement and conservation [11].

Capsicum species are diploids, and most of them have 24 chromosomes (n = x = 12), but several wild species have 26 chromosomes (n = x = 13) [11, 12]. C. annum has 24 chromosomes; usually, two pairs are acrocentric, and 10 or 11 pairs are metacentric or submetacentric [13]. Its nuclear DNA content has 3.38 picograms (pg) per nucleus, which, in relation to other reports, ranged from 2.76 to 5.07 pg. per nucleus [14]. The chili pepper genome ranged from 1498 cm to 2268 cm and approximately two to three times larger than the tomato genome [15, 16].

In 12 Capsicum accessions, a chromosome number of 2n = 2x = 24 was determined, and this ploidy level is well-documented in several Capsicum species [17]. Capsicum species in the wild, such as C. buforum, has a ploidy level of 2n = 2x = 26 [17]. Two distinct evolutionary lines emerged throughout the history of this genus, marked by a significant separation between wild (base number x = 13) and domesticated (base number x = 12) species [17]. Multiple karyotypic formulae in the same species may occur from genetic variances within populations, which are produced by genomic responses to various environments [17]. Individuals in the same group might have different chromosomal races due to chromosomal polymorphism [17].

Plants with more karyotypic symmetry than other members of the same genus are related to those with less symmetry [18]. Even though most Capsicum species have 2n = 24 and have quite similar chromosomal shapes, the genus exhibits a lot of intraspecific and interspecific karyotypic diversity [18].

Karyotypic asymmetry is linked with considerable changes in TLHB and TCL across individuals of the same or nearly related species due to chromosomal modifications such as Robertsonian translocation, inversion, uneven translocations, deletions, and duplications [18]. Exposure to external elements such as climate, soil, temperature, and moisture may cause these changes [18]. C. annum and C. chinense chromosome modifications like translocations, duplications, and deletions have been identified [18]. The karyotypes of Capsicum in the same genus showed more genetic variability, possibly due to their high asymmetry index [19].

Studies of pepper chromosome number and morphology produce essential data for Capsicum taxonomy, which aid in delineating cultivated, semi-cultivated, and wild species and contribute to plant diversity conservation by providing valuable information for breeding and genetic improvement programs of this crop [20, 21].

The diploid chromosomes (2n = 2x = 24) were confirmed for each of the 12 accessions. This ploidy level is well-documented in several Capsicum species [19, 22, 23, 24, 25, 26]. For some wild Capsicum species, such as C. buforum and C. capylopodiume, 2n = 2x = 26 ploidy level has been reported [24]. Throughout the development of this genus, two separate lines arose, as evidenced by a clear divergence between wild (base number x = 13) and domesticated (base number x = 12) species [24]. It was hypothesized that x = 13 lines are inherited from ancestors of the x-12 plants [24].

The karyotypic formula 11M + 1SM was determined in 11 of the examined accessions, with chromosome 12 categorized as submetacentric [19]. The karyotypic formula 12M was observed in the C. frutescens accessions BGC 37, indicating chromosomal polymorphism compared to the other accessions [19]. For several Venezuelan accessions, the karyotypic formula 11M + 1A was reported [22]. At the same time, the formula 11M + 1A in C. chinense accessions was described through conventional cytogenetics in several Brazilian states [20, 27].

Genetic differences within populations, caused by the genomic response to diverse environments, might result in multiple karyotypic formulae in the same species [25]. Chromosomal polymorphism might change the karyotypic pattern of individuals in the same group, resulting in separate chromosomal races [19].

Variances in the form, size, and number of chromosomes are prevalent in populations of the same species or interspecific taxa. These differences are categorized into cytotypes or chromosomal races [19, 20]. Researchers confirmed that such variations are common in the Capsicum genus, whose cytotypes differ primarily in karyotypic formula and chromosomal size [19]. Secondary constrictions were found in the homologous pairs (1 and 12; 6 and 11) of the BGC 01 and BGC 37 C. frutescens accessions, respectively [19]. Prominent secondary constrictions were found in every Capsicum species, ranging from one to four per karyotype [27]. The average chromosomal size measured in various Capsicum species ranged from 3.29 m (BGC 49) to 7.48 m (BGC 54) [19].

Most of the Capsicum species have similarity (2n = 24), and the genus also exhibited intra- and interspecific karyotypic variability [28]. A higher asymmetry index across karyotypes of species in the same genus is associated with more genetic heterogeneity [20]. Capsicum’s chromosomal analysis at the metaphase stage revealed metacentric, submetacentric, acrocentric, or telocentric chromosomes [22, 29].

Capsicum species had symmetrical chromosomal numbers, so more extensive sampling and detailed characterization of the chromosomes, including heterochromatin distribution and sequence identification by in situ hybridization, must be done to distinguish between species that have the same karyotypic formula [19, 30].

Studies on pepper chromosome number and shape provide essential data for Capsicum taxonomy, assisting in the identification of cultivated, semi-cultivated, and wild species, as well as contributing to plant variety conservation by assisting genetic improvement efforts for this genus [31].

4. Genetic diversity and QTLs

Genetic diversity is crucial for Capsicum development and management. Genetic diversity is correlated with average fitness across populations [18, 32]. The robust genetic diversity of Capsicum populations will enable them to adapt to ever-changing environments, be a resource of valuable alleles and genes in the population, and contribute to ecosystem diversity [18, 32]. To date, there are various estimates as to the number of Capsicum species [20, 21, 22, 23, 24, 33, 34, 35].

Capsicum fruits are diverse and vary in form and characteristics. Fruit form has been examined extensively in the Solanaceae family, including tomato, pepper, and eggplant [36, 37, 38]. On chromosomes 2, 3, 7, 8, and 10, allelic variations in the Sun, Ovate, Fascinated (FAS), and Locule Number (LC) genes determine the form of the tomato fruit [36, 39, 40, 41, 42, 43, 44, 45, 46]. Individual alleles of these genes might account for up to 71% of the particular shape variance in a population [46]. Individual alleles of these genes accounted for up to 71% of the particular shape variation in a broad sample of 368 wild and cultivated tomatoes [46]. Fruit weight was strongly co-localized across tomato and pepper QTLs, and a single fruit shape QTL was co-localized, suggesting that conserved components contribute to one, if not both, of the traits [38, 39, 44, 45, 46, 47, 48, 49, 50, 51]. Multiple QTLs for fruit length, width, and the fruit shape ratio (length: width) have been discovered on chromosomes 1–4, 8, 10, and 11 [39, 44, 48, 50]. Two essential fruit QTLs, fs 3.1 (fruit shape) and fe 10.1 (fruit elongation), were linked to chromosome 3 and 10, respectively, in a BC4F2 population segregating for fruit-shaped [44]. These QTLs accounted for 67, and 44% of the variance in fruit form and elongation found in the population, respectively [44]. Fruit trait inheritance in connection to pericarp form, color thickness, and total soluble solids was also investigated [52].

The round form characteristic was governed by a single gene based on segregation ratios. Five QTLs contributing to fruit form and one QTL for pericarp thickness on chromosomes 1, 2, 4, 10, and 3 were determined. This explains the 4 to 26% of the diversity in the Jalapeno recombinant inbred lines [50]. The expression of a gene that resembled the tomato gene Ovate and discovered substantial variations between round and elongated pepper cultivars was compared [51]. Further study was carried out on five domesticated species [53].

Another QTL analysis in 2012 found that two dominant genes regulated fruit mass length, diameter, form ratio, and flesh thickness, with heritability ranging from 38 to 88% [45, 54]. Fruit width was highly heritable, and fruit weight and width were positively associated while examining a pepper germplasm collection from the Caribbean, which was consistent with the QTL study [44, 48, 54]. The heritability of fruit form and flesh thickness was 80% in another mapping investigation [48]. The INRA characterized the phenotype of almost 1300 pepper accessions in their collection for 12 fruit traits; form and color varied across domesticated species, but wild species often featured tiny, elongated fruit [55]. Despite the large number of studies examining pepper fruit form, the use of subjective visual (e.g., elongate, triangular, square, heart) or manual (length/width ratio) measures to define fruit shape was a shortcoming in all of them [55]. With this, software has been created that allows for more objective and reliable assessments of fruit attributes [33, 41].

Disease resistance is also crucial, even if fruit form is one of the most critical features of a cultivar [30]. Cultivated cultivars frequently lack disease resistance due to breeding bottlenecks [30]. Resistance is frequently found in small-fruited wild species and then adopted into larger-fruited commercial cultivars [56, 57]. Through linkage drag or pleiotropic effects, negative horticultural features such as disease resistance can be passed together with beneficial traits like disease resistance [56, 57]. Recent research on tomatoes found a relationship between resistance to the late blight pathogen (Phytophthora infestans) and unfavorable impacts on maturity, fruit size, yield, and plant architecture [58, 59]. In pepper, a link between fruit features and disease resistance for a single strain of P. capsici, a destructive fungus that causes fruit, foliar, and root rot [50, 55]. In an eggplant germplasm population, fruit form was positively linked with disease susceptibility to P. capsica [48, 50]. Negative associations were found between resistance to the bacterium pathogen Pseudomonas syringae (PV) in Kiwi [60]. When transferring disease resistance into commercial cultivars, it is critical to look for possible correlations, linkage drag, and pleiotropic effects [60].

Since their introduction in Mexico, peppers have been subjected to a substantial selection for fruit forms and sizes [61, 62]. Domesticated pepper fruit has an unlimited variety of phenotypic variability [63, 64, 65, 66]. While cousins and landrace peppers are typically tiny and very pungent, domesticated pepper fruit has an endless array of phenotypic diversity [64, 65, 66]. Various regional preferences exist for pepper consumed in most nations and marketplaces [64]. Regional choices have increased morphological variability among market classes [64].

In addition to Capsicum’s genetic diversity, we also analyzed the phylogenetic relationships of 22 Nicotinamide Adenine Dinucleotide Dehydrogenase (NADH dehydrogenase) sequences of Capsicum from 19 different species. NADH dehydrogenase is a flavoprotein-containing oxidoreductase that catalyzes the conversion of NADH to NAD. The enzyme may be found in eukaryotes as a part of the mitochondrial electron transport complex I and in transferring electrons from photoproduced stromal reductants like NADPH and ferredoxin to the intersystem plastoquinone pool. NADH dehydrogenase is the primary enzyme complex in the electron transport chain in mitochondria. Nicotinamide adenine dinucleotide (NAD) is transformed from its reduced form, NADH, to its oxidized form, NAD+ [67].

Phylogenetic analysis using UPGMA Maximum Composite Likelihood with 1000 bootstrap replications revealed that the C. ciliatum, C. lanceolatum, C. lycianthoides, and C. geminifolium grouped together. More so, C. minutiflorum and C. ceratocalyx were strongly clustered together, the same with C. chinensis and C. frutescens (Figure 1).

Figure 1.
Phylogenetic relationships (UPGMA) of 22 species of Capsicum based on NADH dehydrogenase.

C. pubescens, C. galapagoence, C. chacoense, and C. cardenasi formed a cluster adjacent to C. annuum on top and C. baccatum species below (Figure 1). Other Capsicumspecies like C. eximium, C. coccineum, C. flexuosum, and C. hunzikerianum had distinct branches and separated from other Capsicum taxa (Figure 1).

The phylogenetic study on the waxy gene [2] indicated that C. chinense and C. frutescens were grouped together. More so, a study on the trnC-rpoB intron, trnH-psbA intron, and waxy gene sequence data from seven Capsicum spp. also revealed that C. chinense, C. annuum, and C. frutescens grouped in the same cluster [2]. The above grouping supported our Capsicum’s phylogenetic analysis based on NADH Dehydrogenase (Figure 1).

5. Genome organization

Genome sequence information of hot pepper revealed 37,989 scaffolds with an estimated size of 3.48 Gb [68]. The GC content was 35.03%, and there were 34,903 genes with an average exon and intron length of 286.5 pb and 541.6 bp, respectively [68]. These protein-coding genes of Capsicum were relatively the same as other Solanaceae species—tomato (34,771 genes) and potato (39,031 genes) [69, 70, 71].

The genetic maps of tomato and pepper are nearly comparable in length, with 1275 cm in tomato and 1246 cm in pepper [72]. However, it was determined that the average recombination rate/unit of physical distance in pepper and tomato is not the same [72]. This would happen if recombination were limited to homologous genes, as demonstrated in maize [73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83].

Regarding the number of homologous and segregating loci found by a probe, tomato, and pepper genomes differ, with pepper having a higher copy number [84]. The significant number of probes detecting multiple loci in pepper than in tomato might be related to the detection of more loci per probe in pepper, or it could be suggestive of a higher degree of interspecific polymorphism in Capsicum than in the interspecific cross used to generate the tomato map [84, 85, 86].

In plants, an increase in the amount of repetitive DNA has been identified as a cause of genome expansion [68, 87]. Retrotransposons distributed uniformly across gene-rich and gene-poor sections of the genome are likely to explain differences in nuclear DNA content among Solanaceae species [68, 81, 87]. Concerning transposable elements (TEs), Capsicum’s TEs were predominantly composed of long terminal repeats (LTR). Specifically, most of the LTRs were Gypsy elements [68].

AFLP, SSR, RAPD, isozymes, inter-simple sequence repeat (ISSR), restrictions fragment length polymorphism (RFLP), gene-based makers, expressed sequence tag-simple sequence repeat (SCoT and EST SSR), and single nucleotide polymorphism (SNP) have all been used in the study and characterization of genetic diversity, phylogenetic relationships, genotypic variations, selection of parentals and progenies, cultivar identity, phenotypic characteristics, purity, population studies, and resistance to disease in Capsicum species [88, 89].

Chili peppers have been identified, and their germplasm diversity was evaluated using various molecular markers [90, 91]. Rodriguez discovered diagnostic RAPD (randomly amplified polymorphic DNA) producers for four domesticated species (including C. chacoense) but not for C. frutescens in a review [92]. Primarily, isozymes have been used to measure genetic diversity and define their genetic relationships within the genus [93].

Studies in the Solanaceae family linking the genetic maps of tomato and potato, respectively, sparked the discipline of comparative plant genomics in 1998 [94, 95]. The initial analysis discovered that the main difference between the tomato and potato genomes was paracentric inversions, and further investigations revealed that five inversions separated the two species [69, 86, 96]. It was shown that no map of Capsicum has yet been developed that accomplishes the aim of thoroughly defining and saturating the pepper chromosomes [72].

About 655 of the 1007 markers produced could be examined for divergence from single-locus Mendelian ratios [72]. Slightly more than half of the tested subgroup (337 = 50.7%) indicated variation from predicted ratios (p = 0.01), with p values as low as 2.69 × 10–25 in 81 of them (12.2%) [72].

The pepper tomato comparative map can be used in conjunction with the Capsicum, Lycopersicon, and Solanum phylogeny. It can also be used to identify conserved linkage blocks, reconstruct portions of the genome of these species’ most recent ancestor, and, in some cases, determine lineage rearrangements that occurred [69, 71, 72, 97]. Because the number of ad hoc hypotheses utilizing either condition as the ancestral state is the same for pepper and tomato/potato, only two different arrangements can be provided [72]. It was noted that paracentric, as well as pericentric inversions and translocations, were the most common structural changes [72]. Interestingly, all tomato clones examined were hybridized to pepper DNA [72].

There were differences in tomato and pepper genomes regarding the amount of homologous and segregating loci, with pepper having a larger copy number [72]. The increased number of probes identifying multiple loci in pepper compared to tomato might be due to the detection of more loci per probe in pepper or indicative of a higher degree of interspecific polymorphism with Capsicum [72]. Regardless, the discrepancies in copy numbers across the specifics lacked the patterns consistent with systemic duplication [72].

Increases in the quantity of repetitive DNA have been identified as a source of genome extension in plants. A recent study in the Gramineae has revealed a pattern of retroelement increases between the genes of large-genome species compared to smaller-genome species analysis of repetitive DNA in the pepper genome indicated that 5% of the pepper genome was made up of elements with copy numbers >10,000, 26% with copy numbers >150, and 65% single-copy sequences [81, 85, 98, 99, 100]. The blocks of constitutive heterochromatin (7% of total karyotypic length) detected primarily at the telomers of C. annum cannot explain all of the additional DNA in pepper compared to tomato chromosomes [101]. As a result, differences in nuclear DNA content between tomato and pepper are likely to be explained by retrotransposons interspersed evenly across both gene-rich and gene-poor areas of the genome, as shown in the Gramineae [102].

The genetic maps of tomato and pepper are nearly comparable in length, with 1275 cm in tomato and 1246 cm in pepper [73, 74, 75, 76]. Because of the comparable lengths of the genetic maps and the difference in DNA content, the recombination rate per unit of physical distance in pepper and tomato is not the same [73, 74, 75, 76]. This would happen if recombination were limited to homologous genes, as predicted and demonstrated in maize [73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83].

A map of Capsicum has yet to be established that achieves the goal of properly identifying and saturating the pepper chromosomes [72]. Pepper has similar genetic content to tomato in the tomato-pepper investigation [72]. The fundamental difference between the tomato and potato genomes was identified as paracentric inversions, and subsequent research indicated that five inversions separated the two species [71, 72]. The tomato-pepper study also discovered that pepper and tomato had similar genomic content, as evidenced by the presence of pepper sequences that were complementary to all tomato cDNA tested [86]. However, the pepper genome had been significantly rearranged, with numerous pepper chromosomes that contain discrete tomato segments [72]. It was further discovered that the pepper genome had lost parts homologous to the tomato genome, but this did not change the fact that the homoeologous linkage blocks in the pepper genome had been considerably broken [72].

The number of homologous and segregating loci of tomato and pepper genomes differ, with pepper having a higher copy number [72]. The larger number of probes detecting multiple loci in pepper than in tomato might be related to the detection of more loci per probe in pepper, or it could be suggestive of a higher degree of interspecific polymorphism in Capsicum than in the interspecific cross used to generate the tomato map [72, 103]. The differences in copy quantity across the specificity, on the other hand, lack the patterns associated with systemic duplications [72].

In plants, an increase in the amount of repetitive DNA has been identified as a cause of genome expansion [72]. Retrotransposons are distributed uniformly across both gene-rich and gene-poor sections of the genome and may explain the differences in pepper and tomato nuclear DNA content [72]. Tomato and pepper genetic maps are approximately identical in length, with 1275 cm in tomato and 1246 cm in pepper [72]. The difference in the average recombination rate in pepper and tomato may be due to variable lengths of their genetic maps and differences in DNA content [72].

6. Genes of Capsicum

Annotated gene sequences are crucial for breeding and developing varieties for tolerance and resistance to biotic and abiotic stresses and enhancing Capsicum’s agronomic and nutritional traits. NCBI record during the time of this writing showed a total of 1181 annotated Capsicum genes (duplicate copies are included). Specifically, Capsicum chacoense has 132 annotated genes, followed by Capsicum galapagoense (132), Capsicum eximium (132), Capsicum frutescens (131), Capsicum baccatum var. baccatum (131), Capsicum baccatum var. pendulum (131), Capsicum baccatum var. praetermissum (131), Capsicum pubescens (131), and Capsicum lycianthoides (130).

Boswell [104] looked at the inheritance of 16 phenotypes in pepper and discovered seven gene symbols for purple foliage and stem color, blunt fruit apex, bulged fruit base, pendent fruit position, red mature fruit color, strong purple foliage and stem color, and non-clasping fruit calyx [104, 105]. Data was merged from six different maps from the US, Israel, and France to construct an integrated Capsicum genetic map with six distinct progenies and 2262 genetic markers spanning 1832 cm [105, 106].

The first Capsicum gene nomenclature and symbols were published in 1865 [105]. Lippert and colleagues increased the number of genes on the list to 75 [105]. Daskalov published a gene list in Bulgarian with around 90 genes [105]. Greenleaf developed a gene list for pepper breeding based on Lippert and others’ gene lists and included several extra gene symbols for pepper breeders’ use [105, 107, 108]. This gene list includes morphological features, physiological traits, sterility, resistance to diseases, nematodes, and herbicides among Capsicum’s 292 known genes [105, 108]. The Capsicum and Eggplant Newsletter Editorial Board (CENL) proposed the criteria for Capsicum gene nomenclature in 1994 to help standardize and articulate the gene symbols [105]. A list of known genes using these rules, reallocating some gene symbols, and standardizing confusing symbols were compiled [105, 109]. Ninety-two genes have been added to Daskalov and Poulos’ gene list [105, 109]. The suggested gene symbols complied with the Capsicum gene nomenclature guidelines for those features tested for inheritance according to CENL [105, 109]. An attempt was made to fix inaccuracies in earlier lists’ gene symbols and descriptions [105].

Since Webber (1912) explored the inheritance of various phenotypes of Capsicum genes [105]. The inheritance of 16 features in pepper identifies seven gene symbols for seven distinct phenotypes [104]. Following Boswell’s work, pepper inheritance research grew in popularity, with more essential features connected with the increased global significance of pepper production and more induced or spontaneous mutants being produced [104, 105].

More efforts to tag identical genes with molecular markers have been made since the late 1980s [110]. In addition, efforts were made to clone and describe the genes [110].

7. Applications

Medicinal herbs are essential natural medicines for various illnesses [111, 112, 113, 114]. Higher plant natural products have the potential to provide a new reservoir of therapeutic medicines with unique modes of action [114, 115, 116]. Peppers were shown to have elevated amounts of vitamins C and E and provitamin A, carotenoids, and phenolic compounds, all of which contribute to the plant’s overall antioxidant activity and bioactive qualities [117, 118]. Capsaicinoids (vanillylamine) coupled to a branched-chain fatty acid are the most common phenolic compounds discovered in pepper fruits [117, 118, 119]. Capsaicin and dihydrocapsaicin, for example, are responsible for 90% of pepper pungency [120]. The pungency of Capsicum varies depending on the species and cultivar. The concentrations of these chemicals can range from 0 mg/ 100 g in non-pungent cultivars to 664 mg/100 g in pungent cultivars [121]. Capsicum spp. also includes the capsinoids capsiate and dihydrocapsiate, two non-pungent analogs of capsaicin and dihydrocapsaicin, respectively [119]. Flavonol and flavone glycosides, as well as hydroxycinnamic acids, are other phenolic chemicals [119]. Capsicum spp. has many health advantages, and consumption of Capsicum is a part of a regular diet of diverse people of different ethnicities worldwide [119].

Due to bioactive chemicals, pepper (C. annum L.) has been reported to heal various degenerative human ailments [122, 123]. Bell peppers (sometimes called sweet peppers or peppers) are high in phenolic components such as quercetin, luteolin, and capsaicinoids [111, 124, 125, 126]. These phenolic chemicals protect against cancer, diabetes, oxidative stress, cardiovascular disease, and neurodegenerative illnesses, including Parkinson’s and Alzheimer’s [111, 123, 124].

Capsicum spp. are native to Mexico and Central America and have been utilized in traditional medicinal practices by Aztecs and Mayans from pre-Hispanic times [123]. The most notable is the indigenous medicine man Martin de la Cruz’s Libellus de Medicinabilus Indorum Herbtis (Little Book of the Indians’ Medicinal Herbs) [127]. Capsicum spp. were reported to have approximately 32 different health-related uses by the indigenous Mayan inhabitants of Mesoamerica at the turn of the twentieth century, including treatment for arthritis, rheumatism, stomach aches, skin rashes, and relief from dog and snake bites [128]. On the other hand, Capsicum fruits are not just used in Latin America; their medical benefits, as well as their use and production, have expanded worldwide [128]. As a result, Capsicum fruits are cited in the “Blue Beryll,” a traditional Tibetan medical treatise, to improve the digestive warmth of the stomach and as a treatment for edema, hemorrhoids, parasitic protozoa, and leprosy [1, 128].

Furthermore, they are regarded as antispasmodic in Africa, disinfectants, anti-irritants, and antitussive agents for the lungs [129]. Capsicum fruits are used topically for pain, neuropathy, cluster headaches, migraines, psoriasis, trigeminal neuralgia, and herpes zoster [129, 130, 131]. Dyspepsia, lack of appetite, flatulence, atherosclerosis, stroke, heart disease, and muscular tension have all been treated with it [132]. Today, a fifth of the world’s population regularly consumes fresh or dried fruits as spices, food supplements, and additives [132].

Natural bioingredients are increasingly used in food for preservation, shelf life extension, and microbiological safety [111, 115]. Spices are used in a wide variety of meals due to the various phytochemicals they contain [111, 115]. Spices such as ginger, allspice, pepper, nutmeg, cloves, celery leaves, chives, and pepper are produced worldwide [111, 115]. Capsaicin, the main chemical ingredient in spicy peppers, has been shown to exhibit antibacterial action against Gram-negative and Gram-positive spoilage bacteria, as well as pathogenic bacteria [133].

Carotenoids are phytochemicals found in Capsicum that function as scavengers of singlet molecular oxygen, peroxyl radicals, and reactive nitrogen species (RNS), and they protect cells and tissues from reactive oxygen species (ROS) damage [134]. Despite this, Capsicum spp. has a large amount of total antioxidant activity. It is linked not only to its vitamin and carotenoid levels but also to its phenolic composition [117, 118]. C. annum, C. frutescens, and C. chinense, the antioxidant ingredients (carotenoids, flavonoids, phenolic acids, and ascorbic acid), rise in concentration along with the antioxidant activity measured in vitro as the fruit matures [135]. Furthermore, Capsicum has a more potent antioxidant activity than other veggies [135]. Capsaicin exhibits antioxidant properties similar to butylhydroxyanisole (BHA). It can protect human low-density lipoprotein (LDL) from oxidation, as well as block copper ion-induced lipid peroxidation, and reduce the development of thiobarbituric acid reactive substance (TBARS) [136, 137].

Capsaicin has received much attention because of its ability to cause apoptosis in various cancer cell lines, including pancreatic, colonic, prostatic, liver, esophageal, bladder, skin, leukemia, lung, and endothelium cells, while leaving normal cells unaffected [138]. However, because cancer prevention and promotion have been advocated, its role in carcinogenesis remains contentious [139]. The promotor effect appears to be linked to high consumption of capsaicin in the diet [139]. In this regard, a meta-analysis from 2014 recommended that capsaicin use should be modest [140].

In several investigations, Capsicum has various effects on glucose metabolism in vitro and in vivo [123, 140, 141]. Selected pungent and non-pungent Capsicum cultivars have demonstrated significant antioxidant activity as well as a great inhibitory profile on carbohydrate-degrading enzymes like—glycosidase, which is linked to glucose absorption [123, 140, 141].

Eating hot Capsicum spp. may improve postprandial glucose, insulin, and energy metabolism [85]. Other research has discovered that C. chinense (habanero) has a stronger anti-amylase activity than anti-glucosidase activity [85].

The digestive stimulatory activity of hot Capsicum is thought to be linked to the stimulation of saliva and bile production, as well as pancreatic and small intestine digestive enzyme activities [140, 141, 142]. It also boosts saliva production and salivary amylase activity, which aid in the digestion of starch and mucous membrane development in the mouth, throat, and gastrointestinal system [140, 141]. Hot Capsicum has been shown in animal experiments to improve fat digestion and absorption in high-fat-fed animals by stimulating the liver to release bile rich in bile acids [132].

Natural capsaicinoids from chili peppers have gotten much press as topical pain treatments [130, 131, 143, 144]. Capsaicin’s unique ability has been used with lotions, ointments, and patches to treat a variety of pains, including neuropathic pain [130, 131, 145]. Chili peppers and their contents might be helpful and promising in preventing or treating insulin resistance, hypertension, dyslipidemia, and obesity [123, 140].

When tested in animal models, capsaicinoids and other bioactive chemicals from Capsicum appear to have additional health benefits [123, 140]. Supplementing with capsaicin may enhance physical activities such as grid, strength, and endurance performance by boosting live glycogen content [123, 140]. In animal trials, it can also reduce several exercise-induced tiredness indices [146, 147]. The use of spicy chilies in a regular diet has been linked to improved iron levels in the population [123, 140, 146]. In hamsters fed diets containing capsaicinoids, the capsaicinoids may lower total plasma cholesterol, inhibit the development of atherosclerotic plaque, and relax the aorta artery via increasing fecal excretion of acidic sterols [123, 140, 146]. It may also have a positive vascular function and modify plasma lipids [123, 140, 146]. Capsaicin, taken orally or topically, lowers rheumatoid arthritis pain, inflammatory heat, and unpleasant chemical hyperalgesia, according to research examining several therapies for knee osteoarthritis in elderly individuals [123, 130, 140, 146]. Capsaicin is claimed to alter 5-lipoxygenase, a major enzyme involved in the manufacture of the inflammatory mediators’ leukotrienes, in human polymorphonuclear leukocyte cells [140, 141, 146, 148].

8. Conclusion

Capsicum is a well-diverse shrub commonly grown in different parts of the world. It is genetically diverse, with numerous cultivars and taxonomic derivatives. It has a widely described chromosome number of 2n = 24; however, some wild Capsicum species, such as C. buforum, C. capylopodiume, and C. capylopodiume have a ploidy level of 2n = 26. C. frutescens showed karyotypic formulae for 11M + 1SM + 1A and 11M + 1A. Capsicum has a relatively similar genomic content compared to tomato, as evidenced by the presence of Capsicum sequences complementary to many tomato cDNAs. To date, more than a thousand Capsicum genes have been annotated in the GenBank that will aid future research on improving the yield and biotic and abiotic traits of Capsicum. This comprehensive review is essential in understanding Capsicum’s biology, genetics, and genomics toward improving its horticultural traits and nutritional and medicinal values.

Acknowledgments

The authors would like to thank the reviewers and colleagues who provided their valuable comments. Appreciation to the Department of Biology, College of Science and Technology, Adventist University of the Philippines, for the support.

Conflict of interest

The authors declare no conflict of interest.

Duncan Smith

Chapters authored

Related collaborators

Tian Wang

Nicholas King

Caryn Van Vreden

Rachael Terry

Daniel Getts

Amanda Yeung

Meghann Teague Getts

Ariane Davison

Celine Deffrasnes

Luis Munoz-Erazo