Genomic research and genetic improvement of orphan crops: novel strategies for addressing global food security challenges

The United Nations' Sustainable Development Goal to end hunger, achieve food security, and improve nutrition while promoting sustainable agriculture has driven substantial global efforts since the 20^th century, resulting in significant progress, though challenges and uneven advancements persist^[1]. Among the approximately 390,000 known plant species, only 5,000–7,000 are cultivated for food, with just 250 fully domesticated. Notably, 30 crop species provide around 95% of human food and energy needs, leading to increasingly homogenized diets that are high in carbohydrates but low in proteins and micronutrients, undermining nutritional security^[2−6]. Traditional agricultural practices including selective breeding, enhanced cultivation techniques, and fertilization are insufficient to meet the food demands of a growing global population^[7]. To address these challenges, it is imperative to transform and diversify food systems. In this context, the development and utilization of orphan crops, species that have been historically neglected in research and development, have emerged as effective strategies to enhance global agricultural productivity and food security^[8]. Orphan crops serve as a vital complement to conventional staple crops, exhibiting distinct nutritional profiles with unique advantages in proteins, micronutrients, and functional compounds, and possess unique values that supports the achievement of the United Nations Sustainable Development Goals.

Orphan crops, also known as neglected and underutilized species (NUS), are plant species that, despite their significant economic, nutritional, and cultural importance in specific regions, receive limited global cultivation and research attention^[9−11]. These crops are mainly distributed in marginal agricultural zones, including sub-Saharan Africa, South Asia, Southeast Asia, and Latin America. They are valued for their resilience to environmental stresses and rich nutritional profiles, contributing to regional food security, and economic development^[12] (Table 1).

The first Global Plan of Action for the Conservation and Sustainable Utilization of Plant Genetic Resources for Food and Agriculture, adopted in Leipzig by 150 countries in 1996, laid the foundation for the development of 'underutilized plant species' ^[13]. The significance of this plan was further reaffirmed in the subsequent second Global Plan of Action^[14]. The term 'orphan crops' first appeared in academic literature in 1998, with its definition gradually refined to denote 'crops of agricultural significance that suffer from insufficient research investment'^[15]. Since 2009, the usage of this term surged markedly^[16,17]. Recent years have witnessed a substantial expansion in orphan crop research, shifting focus from descriptive studies of traditional agricultural systems and basic trait characterization to genetic improvement and applications in sustainable agriculture.

Orphan crops primarily include cereals, pseudocereals, legumes, and root crops^[18]. Domesticated approximately 11,000 years ago, foxtail millet (Setaria italica) is believed to have originated and undergone major improvement in China, playing a pivotal role in the emergence and prosperity of early Chinese civilizations^[19,20]. Quinoa (Chenopodium quinoa), originating in the Andean region with a 7,000-year cultivation history in South America, is a nutrient-dense, drought-resistant pseudocereal^[21]. Chickpea (Cicer arietinum), the third most cultivated legume in the world, has been farmed for approximately 10,000 years in South Asia and the eastern Mediterranean. Beyond its agronomic importance, chickpea offers high nutritional value and culinary versatility, and ecological benefits, such as soil fertility enhancement, and biodiversity promotion^[22,23]. Yam (Dioscorea spp.), a globally distributed tuber crop cultivated across Africa, Asia, and Latin America, serves as a vital food source with diverse nutritional and medicinal value. Notably, it holds cultural significance in traditional medicine for treating various ailments^[24,25]. Collectively, these orphan crops play indispensable roles in global agroecosystems. They not only provide diverse food resources but also contribute to biodiversity conservation and soil health enhancement. Nevertheless, their full potential remains underexploited due to limited research and institutional attention^[18].

Genetic resources serve as strategic reserves for crop improvement, biodiversity conservation, and climate change adaptation. Their systematic collection and preservation provide diversified gene pools for agricultural breeding, enhancing crop stress tolerance and yield while safeguarding genetic information of wild and endangered species. The National Bureau of Plant Genetic Resources (NBPGR) in India has recorded 26,395 accessions of Sorghum, 25,785 accessions of Minor millets, and 14,904 accessions of Chickpea (https://nbpgr.org.in/nbpgr2023). Additionally, the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) has collected 129,000 accessions from 144 countries, covering Sorghum, Minor millets, chickpea, pigeonpea, and peanut (www.icrisat.org). The International Institute of Tropical Agriculture (IITA) holds the world's largest and most diversified collection of cowpea, with 15,000 accessions, as well as nearly 5,900 accessions of yam and approximately 2,000 accessions of Bambara groundnut (www.iita.org). For Cassava, the International Center for Tropical Agriculture (CIAT) and IITA have preserved 5,965 and 3,700 accessions, respectively, covering major cultivated varieties worldwide (https://alliancebioversityciat.org). The International Potato Center (CIP) maintains the world's largest sweetpotato genbank, with over 5,500 accessions preserved ex-situ, and has also collected 2,529 accessions of nine Andean roots and tubers (ARTCs) (https://cipotato.org/). Some regional institutions also play significant roles in the conservation of specific crops. For instance, the National Tropical Botanical Garden (NTBG) manages the world's largest Breadfruit germplasm collection (https://ntbg.org). The Centre for Pacific Crops and Trees (CePaCT) has preserved approximately 70% of the world's Taro germplasm (around 1,300 accessions) (www.spc.int/resource-centre/centre-for-pacific-crops-and-trees-cepact). Additionally, the Chinese Crop Germplasm Resources Information System (CGRIS) preserves over half of the world's Foxtail millet germplasm (www.cgris.net/home).

Traditional breeding, while not the most optimal strategy for efficient genetic improvement of orphan crops, still holds an irreplaceable position in enhancing their production potential due to its strong environmental adaptability, ecological compatibility, low technical barriers, and cost-effectiveness. The breeding experiences from major cereals can help address technical bottlenecks in the traditional breeding of orphan crops and accelerate their genetic improvement^[12]. In some East African countries, finger millet varieties with 'special' traits are being actively promoted. For instance, iron-rich 'NAROMIL 3' helps alleviate iron-deficiency anemia, while the high-protein 'NAROMIL 5' and 'EUFM-401' improve nutritional intake. The easily breakable 'EUFM 05' reduces farmers' labor burden, and high-yielding 'ACC 14FMB/01WK', 'KNE 688', and 'P224' help ensure better harvests, thereby addressing food security challenges^[26,27]. The Chinese alfalfa (Medicago sativa) variety 'Zhongmu-4' is the most commonly cultivated in northern China due to its well-developed root system, large leaf area, high nutritional value, rapid regrowth, high yield, and salt tolerance, enabling extensive adoption in the Yellow-Huaihe-Haihe River regions^[28]. For chickpeas, mechanically harvestable varieties, such as 'NBeG 47' and 'GBM 2', reduce labor intensity and production costs through optimal podding height and seed yield advantages^[29]. High-oleic peanut varieties, 'Girnar 4' and 'Girnar 5', have been commercially cultivated in Myanmar, Bangladesh, India, South Africa, Mali, and Malawi^[30]. Across Ethiopia, Uganda, Kenya, Nigeria, and India, a high-yielding Orange-Fleshed Sweetpotato (OFSP) variety rich in vitamin A precursors and β-carotene is being promoted to enhance food security by increasing crop yields and consumption rates while reducing malnutrition and child mortality rates. Its roots and leaves are rich in β-carotene, which effectively alleviates vitamin A deficiency (VAD) in children and women of reproductive age^[31,32]. These achievements not only demonstrate the potential of traditional breeding techniques but also lay a solid foundation for the modernization of orphan crops.

Traditional breeding emphasizes the prolonged observation and selection of crop traits over generations, while modern genomics reveals genetic-level variations, providing more precise guidance for breeding efforts. Consequently, the integration of traditional breeding and modern genomics not only compensates for their respective limitations but also offers a more comprehensive technological framework for the rapid improvement and promotion of orphan crops. For instance, in African agroecosystems, traditional local varieties that have been cultivated for generations often exhibit unique adaptability and nutritional value. By analyzing the genomes of these varieties, researchers can efficiently identify genes associated with desirable traits such as disease resistance, drought tolerance, or enhanced nutrition. These genes can then be incorporated into new cultivars, thereby accelerating the breeding process. This synergistic approach underscores the potential of combining conventional practices with cutting-edge technologies to advance the development of orphan crops. For example, based on the genome sequence and resequencing data of pearl millet, researchers have identified 11 parental combinations that have been utilized to produce hybrids exhibiting enhanced performance, as well as 159 parental combinations that have not yet been employed in hybrid breeding programs but are predicted to demonstrate high-yielding hybrid vigor^[33].

The systematic characterization and functional exploitation of superior genetic determinants in orphan crops not only elevates their intrinsic agronomic potential but also fundamentally advances the global agricultural episteme through strategic expansion of phenotypically validated genetic repositories. Recent advances in the characterization of high-oleic acid phenotypes have elucidated key genetic mechanisms in peanut (Arachis hypogaea) and chia (Salvia hispanica). In peanut line 'F435', the high-oleic acid phenotype is co-regulated by two recessive genes, ol1 (AhFAD2A) and ol2 (AhFAD2B), which encode Δ¹² fatty acid desaturases (FAD2) responsible for converting oleic acid to linoleic acid. A SNP (G/A) at position 448 bp in the coding region of AhFAD2A and a frameshift insertion mutation (an additional adenine base) at position 442 bp in AhFAD2B abolish enzymatic activity, thereby increasing the oleic acid-to-linoleic acid ratio^[34−37]. In the natural high-oleic acid mutant lines 'PI342664' and 'PI342666', a novel C/G mutation 301 bp in AhFAD2B similarly reduces its enzymatic function^[38]. Similarly, ShFAD2-1 and ShFAD2-2 from chia have been validated through heterologous expression in yeast to exhibit Δ¹² desaturase activity^[39].

Research on defense-related small molecule peptides has a significant role in enhancing disease resistance in various plant species. The alfalfa antifungal peptide (alfAFP) demonstrates substantial inhibitory activity against Verticillium dahliae, with transgenic potatoes (S. tuberosum) expressing alfAFP showing robust disease resistance in greenhouse trials^[40]. Two antimicrobial peptides, Ac-AMP1 and Ac-AMP2, derived from Amaranthus caudatus, exhibit broad-spectrum inhibition of plant pathogenic fungi and Gram-positive bacteria at low concentrations^[41]. Additionally, transgenic tobacco plants expressing the antimicrobial peptide gene Ah-AMP from Amaranthus hypochondriacus showed significantly reduced disease indices when infected by Pseudomonas solanacearum and Phytophthora parasitica, the causative agent of tobacco black shank^[42].

Heterologous expression studies have demonstrated the functional roles of genes from various orphan crops in enhancing stress tolerance and other agronomic traits in model plants. Expression of the sweetpotato papain-like cysteine protease SPCP2 in Arabidopsis thaliana induced early flowering, abnormal pistil development, reduced seed viability, and enhanced salt and drought tolerance^[43]. Similarly, overexpression of the mung bean (Vigna radiata) transcription factor gene VrDREB2A (Dehydration-responsive element-binding protein 2) in Arabidopsis improved drought and salt stress tolerance by activating DRE cis-element-dependent stress-responsive genes^[44]. In parallel, overexpression of gene EcbHLH57 (Basic helix-loop-helix) cloned from finger millet in tobacco significantly enhanced salinity and drought tolerance, and root growth while upregulating the expression of stress-responsive genes (LEA14, rd29A, rd29B, SOD, APX, ADH1, HSP70, and PP2C), conferring comprehensive multi-stress resilience^[45]. Furthermore, GsZFP1, encoding a Cys2/His2-type zinc finger protein from wild soybean (Glycine soja), significantly enhanced salt and drought tolerance when overexpressed in alfalfa^[46].

Studies on salt and alkali tolerance mechanisms have identified key genes and pathways that confer resilience to these abiotic stresses in several orphan crops. In quinoa, genotype-dependent Na⁺ exclusion under salt stress was mediated by the synergistic action of CqHKT1 (High-affinity K⁺ transporter 1) and CqSOS1 (Salt overly sensitive 1)^[47]. The sorghum alkali tolerance gene AT1 (Alkali tolerance 1), encoding a Gγ subunit, enhances saline-alkali tolerance by modulating H₂O₂ efflux^[48]. Overexpression of the gene SiGRF1 (General regulatory factor) cloned from foxtail millet cultivar 'Yugu1' in Arabidopsis improved salt tolerance^[49]; however, subsequent studies demonstrated its negative regulatory role in drought tolerance and root growth^[50]. The wild soybean ion transporter gene GmCHX1 (Cation/H⁺ exchangers) improved Na⁺/K⁺ homeostasis and salt tolerance in the salt-sensitive line 'C08'^[51]. In alfalfa, overexpression of endogenous MsRCI2D and MsRCI2E (Rare cold-inducible 2) enhanced salt tolerance by regulating the expression of key ion homeostasis genes (SOS1, NHX1, and HKT)^[52]. Meanwhile, overexpression of MsNIP2 (Nodulin 26-like intrinsic proteins) exhibited reduced water loss and electrolyte leakage under salt stress despite higher Na⁺ accumulation, alongside increased plant height and branching^[53]. The transcription factor MsSPL12 (Squamosa promoter-binding protein-like) was shown to enhance alfalfa salt tolerance through multi-pathway coordination, including reduced Na⁺ accumulation, elevated antioxidant enzyme activity, and regulation of downstream gene expression^[54].

The mung bean ubiquitin-conjugating enzyme VrUBC1 (Ubiquitin conjugating) enhances osmotic stress tolerance by modulating the ABA pathway and interacting with RING E3 ligases^[55]. The ascorbate peroxidase gene DaAPX from yam, when expressed in transgenic Arabidopsis, significantly improves cold tolerance, waterlogging resistance, and antioxidant capacity^[56]. The PgDREB2A gene, cloned from Pearl millet, encodes a protein lacking a typical PEST degradation signal motif, conferring enhanced tolerance to high ionic and osmotic stress in transgenic tobacco plants^[57].

Gene-editing technology, notably CRISPR/Cas9, has emerged as a powerful tool for improving crop traits such as stress resilience, higher yields, nutritional value, and accelerated domestication. Cassava, a starchy tuber crop characterized by large storage roots, serves as both a dietary staple and a multi-billion-dollar source of industrial starch. Nevertheless, conventional cassava breeding has been constrained by protracted phenotyping intervals and genotype-specific limitations in environmental plasticity. Recent advancements in CRISPR/Cas9 have provided innovative solutions to these limitations, enabling precise modifications to enhance cassava's agronomic and industrial potential.

In cassava, CRISPR/Cas9 has been applied to modify starch biosynthesis pathways, yielding significant improvements in root starch properties. Targeted mutations in protein targeting starch (PTST1) or granule-bound starch synthase (GBSS) genes have substantially reduced or eliminated amylose content in root starch^[58]. Similarly, editing of starch branching enzyme 2 (SBE2) increased amylose and resistant starch levels in mutants, markedly improving the physicochemical properties of storage root starch^[59]. In the widely grown cultivar 'South China No. 8' (SC8), CRISPR/Cas9-induced knockout of the MeMinD gene disrupted amyloplast division, resulting in greater starch granule quantity and a wider size distribution, offering a novel approach to tailoring cassava starch for specific applications^[60].

Beyond starch quality, CRISPR/Cas9 has proven effective in strengthening cassava resistance to biotic stresses. In the cultivar '60444', editing of the ncbp-1, ncbp-2, and ncbp-1/ncbp-2 (novel cap-binding protein) genes produced mutants with reduced foliar symptoms of cassava brown streak disease (CBSD), alongside decreased severity and incidence of root necrosis^[61]. To combat bacterial susceptibility in 'SC8', precise editing of the effector-binding element (EBE) within the MeSWEET10a promoter suppressed disease symptoms and bacterial proliferation, without compromising yield-related traits^[62]. Additionally, knocking out the CYP79D genes across multiple varieties significantly lowered cyanogen content in leaves and roots, improving the crop's safety for human consumption^[63]. These examples illustrate the transformative potential of CRISPR/Cas9 in enhancing both the resilience and safety of cassava.

The application of CRISPR/Cas9 extends well beyond cassava, offering substantial benefits for a range of orphan crops. In sweet potato, editing of the granule-bound starch synthase I (IbGBSSI) and starch branching enzyme II (IbSBEII) genes in the starch-rich 'Xushu22' and carotenoid-rich 'Taizhong6' varieties altered amylose-to-amylopectin ratios and chain lengths, without affecting total starch content^[64]. In groundcherry (Physalis pruinosa), targeted modifications to the SELF-PRUNING (SP), SELF-PRUNING 5G (SP5G), and CLAVATA (CLV) genes increased fruit number by 50% and fruit weight by 24%, improving both yield and quality^[65]. Additionally, CRISPR-Cas9 gene editing was used to validate the function of the Less Shattering1 (SvLes1) gene product in regulating seed shattering. This gene was found to be non-functional in green millet due to the insertion of a retrotransposon in its domesticated allele SiLes1-TE^[66]. In soybean (W82), CRISPR/Cas9-generated E1La loss-of-function mutants (tof4CR) at the Time of flowering 4 (Tof4) locus exhibited earlier flowering, accelerated maturity, and altered yield-related traits, confirming E1La's role in suppressing flowering and enhancing high-latitude adaptation in wild soybean^[67].

Further examples highlight the versatility of CRISPR/Cas9 across other orphan crops. The CRISPR/Cas12i.3 system was used to edit two BRACHYTIC2 (BR2) homologs (PmBR2a and PmBR2b) in broomcorn millet (Panicum miliaceum), producing dwarf, high-density-tolerant germplasm with shortened internodes and unaltered grain size or hundred-grain weight^[68]. CRISPR/Cas9 knockout of SbBADH2 in sorghum created fragrant varieties with a distinct jasmine-like aroma in seeds and leaves^[69], while knockout of AT1 significantly enhanced salt-alkali tolerance and improved yield and biomass^[48]. Modification of SbSLT1 and SbSLT2 via CRISPR/Cas9 reduced strigolactone (SL) root exudation, suppressing Striga gemination and parasitism without compromising crop growth or yield^[70]. CRISPR/Cas9 knockout of SaHSF1 in American black nightshade (Solanum americanum) impaired thermotolerance and downregulated heat shock protein (HSP) genes^[71], while prickleless (PL) alleles engineered in Solanum species suppressed prickle development without pleiotropic effects^[72]. These diverse applications underscore the capacity of CRISPR/Cas9 to enhance yield, stress tolerance, and quality traits across orphan crops. As the technology continues to advance, its role in improving orphan crops is poised to expand, contributing significantly to global food security and sustainable agriculture. By enabling precise, efficient modifications, this technology addresses longstanding challenges in crop improvement, offering a promising pathway to meet the demands of a growing population and a changing climate.

Orphan crops have historically suffered from insufficient genetic and molecular genetic resources due to the lack of complete genome sequences and high-throughput phenotyping platforms, which hindered appropriate germplasm selection over the past decades^[73]. Recent advances in sequencing technologies have significantly increased sequencing throughput and reduced costs, providing profound opportunities for genomics breeding of orphan crops. Research initiatives led by international consortia, which have propelled orphan crop research into the whole-genome era, including the African Orphan Crops Consortium (AOCC; http://africanorphancrops.org), Crops of the Future Collaborative (https://foundationfar.org/consortia/crops-of-the-future-collaborative), International Crops Research Institute for the Semi-Arid Tropics (ICRISAT; www.icrisat.org), Centre of Excellence for Plant and Microbial Science (CEPAMS; www.cepams.org), Consultative Group on International Agricultural Research (CGIAR; www.cgiar.org), and International Weed Genomics Consortium (IWGC; https://foundationfar.org/what-we-do/consortia)^{[3,8,12,74,75]} (Table 2). Utilizing whole-genome sequencing to explore germplasm resources is a key strategy for improving orphan crops, especially when investigating wild germplasm that may contain useful genetic resources lost during domestication. The limitations of conventional techniques in germplasm utilization have hindered the development of some orphan crops with scarce genetic diversity. Therefore, integrating whole-genome information with advanced breeding methods can effectively overcome these limitations, ultimately transforming orphan crops into sustainable crop resources with broad adaptability and high agricultural value.

Orphan crops often possess unique agronomic traits absent in conventional crops. Resequencing studies in several orphan crops have laid the foundation for understanding their population structure and domestication history, facilitating genome-wide association studies (GWAS) to identify candidate genes for key agronomic traits, clarify the sources of genetic variations, and enable the development of molecular markers for marker-assisted breeding^[66,76−79]. Significant genetic variation exists among individuals within the same species due to geographic and environmental factors. However, a single reference genome cannot fully capture this diversity. Pangenome analyses, which integrate genomic data from multiple accessions, construct a comprehensive framework comprising core and variable genomes, thereby revealing genetic diversity and evolutionary patterns within orphan crop populations. Such advances not only deepen our understanding of the genetic architecture of orphan crops but also provide critical theoretical and technical support for breeding programs, substantially accelerating their genetic improvement^{[20,22,66,80−83]}.

International cassava improvement research was initiated by IITA and CIAT in the early 1970s, with the objective of developing high-yielding cassava varieties resistant to major pests and diseases, while also reducing pest-related losses through biological control and integrated pest management. In Sub-Saharan Africa, this research resulted in the development of several elite genotypes exhibiting resistance to cassava mosaic disease and cassava bacterial blight, alongside high yield, stability, and favorable consumer acceptability. From the late 1970s to the 1980s, these improved varieties were successfully disseminated following localized testing, significantly increasing yields (by 50%–100% without the use of fertilizer) and enhancing disease resistance and agroecological adaptability, thereby providing critical support for sustainable agricultural development in the region^[84].

AOCC is an international initiative dedicated to enhancing the productivity, nutritional value, and sustainability of African orphan crops through genomic research, capacity building, and crop variety improvement. This endeavor aims to strengthen food security and advance sustainable agricultural development across the African continent. To achieve these objectives, the consortium collaborates with prominent global institutions, including the World Agroforestry Centre (ICRAF), the University of California, Davis (UC Davis, USA), and CGIAR. A cornerstone of AOCC's mission is the genomic sequencing of 101 traditional African food crops, which provides a scientific basis for their genetic enhancement. The ultimate vision of the AOCC is to ensure that improved varieties and cultivars, developed using genomic insights, are made available to farmers for cultivation. To date, reference genome sequences for at least ten orphan crops have been published in the academic literature, marking significant progress in this initiative. In addition to its research efforts, the AOCC facilitates capacity-building programs for African plant breeders, utilizing ICRAF as a training hub. These programs are designed to equip participants with advanced breeding techniques, thereby fostering agricultural innovation and supporting the sustainable development of the region^[3,85−89].

The Roots, Tubers, and Bananas Research Program (RTB), initiated in 2012, is a collaborative initiative led by CIP in partnership with four CGIAR research centers—Bioversity International, CIAT, IITA, and CIP itself—alongside the French Agricultural Research Centre for International Development (CIRAD). This program aims to enhance the production efficiency, sustainability, and utilization of root and tuber orphan crops, including cassava, sweet potato, yam, and other related species. These orphan crops, typically underrepresented in global agricultural research, are rich in essential nutrients such as provitamin A carotenoids, thereby playing a pivotal role in improving nutrition and food security in developing countries. As primary dietary staples for hundreds of millions of individuals in these regions, they are highly valued for their exceptional adaptability to adverse growing conditions, significantly contributing to sustainable agricultural development^[90]. Through these international cooperation initiatives, the research and application of orphan crops have been significantly advanced, thereby making substantial contributions to global food security, and the development of sustainable agriculture (Fig. 1).

Figure 1. 

Global distribution and international cooperation of orphan crops.

While conventional breeding has played a foundational role in improving orphan crops, its limited efficiency, precision, and adaptability increasingly fail to address urgent demands posed by climate change and food security. To overcome these challenges, integrated strategies are essential, including accelerating genome characterization and pangenome research through high-throughput sequencing, elucidating genetic diversity via multi-omics analyses (e.g., transcriptomics, metabolomics, proteomics, spatial omics), leveraging CRISPR/Cas9-mediated gene editing for precision enhancement of key trait genes, and establishing global germplasm repositories to preserve genetic diversity; strengthening international collaboration and knowledge exchange will provide material and technical support for developing and disseminating novel varieties. Concurrently, comprehensive measures, are critical to enhancing orphan crops' yield, stress resilience, and market value, such as promoting locally adapted cultivation practices, unlocking food and health application potentials, and implementing targeted policy frameworks.