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Frontiers in Genetics | www.frontiersin.org 1 September 2020 | Volume 11 | Article 581357
REVIEW
published: 18 September 2020
doi: 10.3389/fgene.2020.581357
Edited by:
Jiayin Pang,
University of Western Australia,
Australia
Reviewed by:
Nicolas Rispail,
Spanish National Research Council,
Spain
Eric Von Wettberg,
University of Vermont, UnitedStates
*Correspondence:
Gyuhwa Chung
chung@chonnam.ac.kr
Hon-Ming Lam
honming@cuhk.edu.hk
Specialty section:
This article was submitted to
Evolutionary and Population
Genetics,
a section of the journal
Frontiers in Genetics
Received: 08 July 2020
Accepted: 31 August 2020
Published: 18 September 2020
Citation:
Ku Y-S, Contador CA, Ng M-S, Yu J,
Chung G and Lam H-M (2020)
The Effects of Domestication on
Secondary Metabolite
Composition in Legumes.
Front. Genet. 11:581357.
doi: 10.3389/fgene.2020.581357
The Effects of Domestication on
Secondary Metabolite Composition
in Legumes
Yee-ShanKu1, CarolinaA.Contador1, Ming-SinNg1, JeongjunYu2, GyuhwaChung2* and
Hon-MingLam1
*
1 Centre for Soybean Research of the State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese
University of Hong Kong, Shatin, China, 2 Department of Biotechnology, Chonnam National University, Yeosu, South Korea
Legumes are rich in secondary metabolites, such as polyphenols, alkaloids, and saponins,
which are important defense compounds to protect the plant against herbivores and
pathogens, and act as signaling molecules between the plant and its biotic environment.
Legume-sourced secondary metabolites are well known for their potential benets to
human health as pharmaceuticals and nutraceuticals. During domestication, the color,
smell, and taste of crop plants have been the focus of articial selection by breeders.
Since these agronomic traits are regulated by secondary metabolites, the basis behind
the genomic evolution was the selection of the secondary metabolite composition. In this
review, wewill discuss the classication, occurrence, and health benets of secondary
metabolites in legumes. The differences in their proles between wild legumes and their
cultivated counterparts will beinvestigated to trace the possible effects of domestication
on secondary metabolite compositions, and the advantages and drawbacks of such
modications. The changes in secondary metabolite contents will also bediscussed at
the genetic level to examine the genes responsible for determining the secondary
metabolite composition that might have been lost due to domestication. Understanding
these genes would enable breeding programs and metabolic engineering to produce
legume varieties with favorable secondary metabolite proles for facilitating adaptations
to a changing climate, promoting benecial interactions with biotic factors, and enhancing
health-benecial secondary metabolite contents for human consumption.
Keywords: legume, domestication, secondary metabolite, defense, health benet
INTRODUCTION
Climate change, farmland deterioration, and the resulting food insecurity are major challenges
facing the world. An increase in food supply is required to feed the expanding human population.
e cultivation of high-yield crops has been used as a strategy to improve food supply. Grain
legumes have been suggested as the potential solution to maintaining food and protein security
(Considine etal., 2017). Legumes are also benecial for sustainable agriculture due to the reduced
release of greenhouse gases compared to other crops (Stagnari et al., 2017). Besides the benecial
eects on the improvement of soil fertility, legumes could enhance the resistance of soil to
ecosystem disturbance, possibly due to the enhanced soil food web complexity (Gao etal., 2020).
Ku et al. Legume Domestication and Secondary Metabolites
Frontiers in Genetics | www.frontiersin.org 2 September 2020 | Volume 11 | Article 581357
In agriculture, legumes are common candidates for crop rotation
for promoting the growth of other crops such as cereals (Bagayoko
et al., 2000; Uzoh et al., 2019). In addition, legumes produce
unique secondary metabolites such as isoavones, which are
benecial to human health (Gepts et al., 2005; Ku et al., 2020).
Legumes are known to protect humans from chronic diseases,
including cardiovascular diseases, diabetes, obesity, osteoporosis,
or even cancer (Kushi etal., 1999; Al-Anazi et al., 2011). Based
on the mode of consumption, legumes can be classied into
four groups: oil seeds, pulses, vegetable crops, and feed crops
(McCrory et al., 2010). Examples of oil seeds are soybean and
peanut (McCrory et al., 2010). Pulses are legumes, which are
exclusively harvested as dry seeds, such as chickpea, lentils, and
peas. Green bean and garden pea are examples of vegetable
crops while clover and alfalfa are examples of feed crops (McCrory
et al., 2010). Human selection of legumes during domestication
has resulted in the alteration, and even loss of diversity, of
secondary metabolite contents in these crops, directly and indirectly
through the selection pressure on the genes that control the
production of secondary metabolites. Understanding the dierences
in secondary metabolites, and the underlying genetic dierences,
between the domesticated legume cultivars and their wild
progenitors would promote the preservation of legume accessions,
which possess the genes for the biosynthesis of benecial secondary
metabolites. is knowledge will facilitate breeding programs
and metabolite engineering to produce legume crops with favorable
traits for adapting to the changing climate and for human
pharmaceutical/nutraceutical use.
SEVERAL DOMESTICATION-RELATED
TRAITS ALTERED THE SECONDARY
METABOLITE CONTENTS
Domestication traits refer to morphological, biochemical,
developmental, or physiological traits that are dierent between
domesticated plants and their immediate wild progenitors
(Abbo et al., 2014). A key part of domestication is the
improvement of crop yield and harvestability compared to
the wild progenitors (Dehaan etal., 2016). Several crop traits,
including pod shattering, peduncle length, oral color, days
to owering, 100-seed weight, pod length, leaf length, leaf
width, and seed number per pod, have been regarded as
domestication-related traits (Lo et al., 2018).
Besides yield and harvestability related traits, other
agronomic traits, such as seed size, appearance, and taste,
are also subject to selection by breeders. ese traits could
be regarded as improvements due to post-domestication
selection (Abbo et al., 2014). It has been suggested that the
selection for larger seeds is related to facilitating single-seed
planting (Kaplan, 1981). Breeders have also selected seeds of
light colors. e ease of sowing and religious reasons have
been proposed to bebehind such conscious selections (Heiser,
1988). erefore, seeds of modern legumes tend to have larger
sizes and lighter colors compared to their wild counterparts.
Moreover, the bitter taste of seeds has been intentionally
eliminated through breeding (Muzquiz et al., 1994). Behind the
loss of bitter taste is the loss of the corresponding bitter-tasting
secondary metabolites such as alkaloids (Muzquiz etal., 1994).
During domestication, secondary metabolite compositions
which facilitate cultivation and improve the appearance and
taste of food grains were intentionally selected for by breeders.
In some cases, the secondary metabolite composition may
be unintentionally selected due to the close proximity of the
genes or quantitative trait loci (QTLs) for secondary metabolite
biosynthesis to those regulating other traits such as major
nutrients and yield. e selection of favorable cultivation areas
and the protection by breeders during crop growth limit natural
selection pressures due to abiotic and biotic stresses. Domestication
brings forth better yield, better taste, and better appearance but
also reduces the availability of secondary metabolites in legumes.
As a result, domesticated legumes are usually less resistant to
biotic stresses compared to their wild counterparts (Muzquiz
et al., 1994; Pavan etal., 2016; Bazghaleh et al., 2018; Abraham
etal., 2019). e reduced availability of health-benecial secondary
metabolites (Muzquiz etal., 1994; Wang etal., 2010; Fernández-
marín et al., 2014; Kaur et al., 2019) also limits the potential
of legumes as sources of bioactive compounds for pharmaceutical
use. For the growth of the legume plants, the loss of the secondary
metabolites in modern cultivars possibly renders the plants more
susceptible to abiotic stress and biotic stress. e importance
of the secondary metabolites to combating these stresses will
be introduced in section “e Roles of Secondary Metabolites
in Combating Abiotic and Biotic Interactions.”
INTRODUCTION TO SECONDARY
METABOLITES IN LEGUMES
Denition of Plant Secondary Metabolites
Secondary metabolites are organic compounds derived from
primary metabolism that serves key roles in defense and signaling
in plants. ey contribute to adaptive traits and ecological
tness, including defense mechanisms, tolerance to abiotic/biotic
stresses, and interactions with insect pollinators, root-associated
microbes, and herbivores. In contrast, primary metabolites are
essential for cellular functions, such as growth, development,
and reproduction. For example, secondary metabolites can attract
insects for pollination or symbiotic rhizobia for nitrogen-xing
nodule formation. ey can also bepart of the defense mechanisms
against herbivores, disease-causing bacteria, fungi, viruses, and
parasites. ere are also a wide range of secondary metabolites
with pharmaceutical, nutraceutical, and toxicological values for
humans (Wink, 2013). e contents of secondary metabolites
vary among dierent plant species (Böttger etal., 2018). Legumes
are rich in secondary metabolites, such as polyphenols, alkaloids,
and saponins (Gupta, 1987).
The Health Benets of Secondary
Metabolites From Legumes
In the recent past, many secondary metabolites in legumes
were considered non-nutritive. For example, tannins,
Ku et al. Legume Domestication and Secondary Metabolites
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glycosides, alkaloids, and saponins affect the digestibility of
beans (Gupta, 1987). However, more and more evidence
suggests there are health benefits from the secondary
metabolites of legumes (Dixon and Sumner, 2003). The
health benefits of carotenoids, polyphenols, alkaloids, and
saponins, all abundant in legumes, are discussed below and
summarized in Tab l e 1 .
Carotenoids
Carotenoids are a type of tetraterpenoids, ranging from bright
yellow and orange to red, found in algae, photosynthetic bacteria,
and plants, including carrot, pumpkin, tomato, sweet potato,
and papaya. ey can be classied into two groups, carotenes
and xanthophylls (Roberts et al., 2009). Xanthophylls dier
from carotenes by having oxygenated substituents in their
molecules (Roberts etal., 2009). Carotenoids with unsubstituted
β-rings, including α-carotene, β-carotene, and β-cryptoxanthin,
act as provitamin A (Roberts et al., 2009). e carotenoid
compositions in various legume seeds have been previously
summarized (Tee etal., 1995). Lutein and zeaxanthin constitute
the macular pigments in the retina of the mammalian eye.
e oxygenated nature of the lutein and zeaxanthin molecules
provides antioxidative protection for the eye from damage by
free radicals (Roberts etal., 2009). e prevention of age-related
macular degeneration by the consumption of carotenoid-rich
foods has been recommended (Bernstein et al., 2016).
Polyphenols
Polyphenols are the major determinants of tissue colors, and
generally possess antioxidative activities (Abbas et al., 2017).
Polyphenols in plants can be classied into two groups: phenolic
acids and avonoids (Abbas et al., 2017). e occurrence and
TABLE1 | Classication of secondary metabolites in legumes and their benets to human health.
Groups Sub-groups Examples in legumes Occurrence in
legumes
Benet(s) to human health References
Polyphenols Flavonoids Quercetin, kaempferol Widely distributed Reduction in ischemic heart
disease, reduction in body
weight
(Knekt etal., 2002)
Isoavones Genistein, daidzin Soybean seeds Phytoestrogen, antioxidant,
antimicrobial and anti-
inammatory properties,
reduction of risk in
cardiovascular diseases,
diabetes, obesity, and
osteoporosis
(Křížová etal., 2019)
Catechin Catechin, epicatechin,
gallo-catechin
Broad bean, chickpea,
cowpea, kidney-bean,
lentil, peanut
Reduction in heart disease,
improvement of sperm motility
and viability
(Arts etal., 2000;
Hollman and Arts, 2000;
Ojwang etal., 2013; Dias
etal., 2016; López-cortez
etal., 2016; Quintero-
soto etal., 2018)
Anthocyanins Pelargonidin, cyanidin,
malvidin, petunidin
Widely distributed Antioxidant and anti-
inammatory properties, lipid
peroxidation, DNA cleavage
protection
(Acquaviva etal., 2003;
Pietta etal., 2003; Rossi
etal., 2012)
Terpenoids and steroid Triterpenoid saponins Saponins Chickpea, soybean,
lentils, peanut, common
bean, and alfalfa sprouts
Reduction of cholesterol
content, antimicrobial and
anti-cancer properties
(Shi etal., 2004, 2014;
Hassan etal., 2010; Man
etal., 2010; Marrelli
etal., 2016)
Tetraterpenes Carotenoids Widely distributed Antioxidant, better visual
function, reduction of
cardiovascular diseases
(Voutilainen etal., 2006;
Roberts etal., 2009)
Alkaloids Quinolizidine alkaloids (QA) Sparteine Lupinus spp. Antimicrobial properties (Romeo etal., 2018)
Pyrroloindole alkaloids Physostigmine Ordeal bean Treatment of Alzheimer’s
disease and Parkinson’s
disease
(Zhu etal., 2014; Kumar
etal., 2015)
Peptides Polypeptide Lunasin Soybean anti-inammatory properties,
reduction of cholesterol
content, antioxidant,
anticancer and anti-
atherosclerotic activities
(Jeong etal., 2002,
2003, 2007, 2009; Hsieh
etal., 2017; Fernández-
tomé and Hernández-
ledesma, 2019)
Protease inhibitors Angiotensin-I converting
enzyme inhibitors
Pea, chickpea, mung
bean, soybean, lentil
Lowering blood pressure and
risk of heart failure
(Zhang etal., 2018)
Amines Polyamine spermine, spermidine Common bean, white
clover, mung bean
Antioxidant activities,
reduction of cardiovascular
diseases
(Soda, 2010; Menéndez
etal., 2019; Muñoz-Esparza
etal., 2019)
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health benets of phenolic acids in grain legumes have been
previously summarized (Singh etal., 2017). Flavonoids are classied
into several sub-classes: avones, avonols, avanones, avanonols,
anthocyanins, avanols, and isoavones (Ku etal., 2020). Among
avonoids, isoavones are only found in legumes. Flavonoids
have multiple functions in plants, for example, mediating the
responses to biotic and abiotic stresses, controlling the transport
of auxins, acting as UV radiation-absorbing pigments to protect
the plant against UV damage, attracting pollinating insects,
interacting with rhizobia to initiate nodulation for symbiotic
nitrogen xation, and regulating defense against pathogens and
herbivores through phytoalexin activities (Kumar and Pandey,
2013). For human health, it has been reported that avonoids
can act as protectants against cellular oxidation, inammation,
viral infections, and cancer (Kleemann etal., 2011). e molecular
mechanisms of the health benets of avonoids have been recently
reviewed (Ku et al., 2020).
Alkaloids
Alkaloids are nitrogen-containing organic heterocyclic
compounds that are biologically active. Many alkaloids have
pharmaceutical properties. For example, some alkaloids were
found to have anti-malarial activities (Onguéné et al., 2013),
anticancer activities (Gupta etal., 2015), and abilities to facilitate
blood circulation in the brain and to prevent stroke (Kumar
and Khanum, 2012). Moreover, several studies reported that
alkaloids have potential therapeutic eects on neurodegenerative
diseases, such as Alzheimer’s disease, Parkinson’s disease, and
Huntington disease (Amirkia and Heinrich, 2014).
Saponins
Saponins are a group of terpenoids found in plants, including
onion, ginger, garlic, ginseng, fenugreek, and legumes (Oakenfull,
1981; Sauvaire etal., 1996). ese crops are important sources
of saponins in the human diet (Oakenfull, 1981; Sauvaire etal.,
1996). Chickpea, soybean, lentils, peanut, garden pea, broad
bean, and alfalfa are rich in saponins (Oakenfull, 1981). e
antibacterial and foaming properties of saponins led to the
use of saponins as vaccine adjuvants (Marciani, 2018). In the
human body, saponins can bind to bile salts to reduce cholesterol
absorption (Marrelli et al., 2016). Moreover, in rats, it was
shown that a saponin-rich diet resulted in the reduction of
body weight, total cholesterol, triglycerides, very-low-density
lipoproteins (VLDL), and low-density lipoproteins (LDL) in
serum (Latha et al., 2011; Reddy et al., 2012). Alfalfa saponin
extract (ASE) was found to have cholesterol-lowering eects
(Wang et al., 2011; Marrelli et al., 2016). e treatment of
rats with ASE led to the enhanced expression of cholesterol
7-alpha-hydroxylase (Cyp7a1), an enzyme involved in the bile
acid biosynthetic pathway in the livers of hyperlipidemic rats
(Marrelli et al., 2016). Besides, ASE treatment also enhanced
the expression of low-density lipoprotein receptor (Ldlr), which
promotes the uptake and clearance of LDL cholesterol in plasma
(Marrelli et al., 2016). Moreover, saponins also have anti-
microbial and antioxidant properties, and exhibit cancer-related
immunomodulatory eects (Avato et al., 2006).
The Roles of Secondary Metabolites in
Combating Abiotic and Biotic Interactions
Polyphenols
Plant roots communicate actively with the soil microbes for
mutualistic cycles. Flavonoids are important signaling molecules
for the legume-microbe interactions. e ability to form nitrogen
xing nodules with rhizobia is a unique characteristic of legumes
(Hirsch et al., 2001). Such mutualism between legume and
rhizobium is initiated by avonoids. Flavonoids released from
roots attract rhizobia to migrate toward the roots and stimulate
the nod genes, which are essential genes to synthesize Nod
factors for infecting the plants (Spaink, 1995). Flavonoids in
the root exudates of various legumes for attracting rhizobia
have been summarized in a previous review (Haldar and
Sengupta, 2015). Moreover, avonoids stimulate the germination
of mycorrhizal fungus spores and enhance hyphal growth
(Abdel-lateif etal., 2012). Mycorrhizal fungi form hyphae which
penetrate plant roots for the transport of nutrients in rhizosphere
to the host plant (Harrison, 2005).
e importance of polyphenols to combating abiotic stress
has been discussed in recent reviews (Di Ferdinando etal., 2014;
Isah, 2019; Sharma etal., 2019). e antioxidating characteristics
of polyphenols help alleviate the oxidative stress brought forth
by abiotic stress (Di Ferdinando et al., 2014; Isah, 2019; Sharma
et al., 2019). A recent method for screening legume crops for
abiotic stress tolerance suggested the accumulation of anthocyanin,
which is also an osmolyte, as one of the indicators of abiotic
stress tolerance of legume crops (Sinha et al., 2020).
Strigolactones
Based on the molecular structure, strigolactones belong to a group
of lactone, which is derived from carotenoid (Jia et al., 2018).
Functionally, strigolactones are plant hormones that are released
by roots to attract symbiotic arbuscular mycorrhizal fungi and
induce the germination of parasitic weed seeds (Jia et al., 2018).
Strigolactones have been identied from a broad range of legumes,
including Arachis hypogaea, Astragalus sinicus, Cicer arietinum,
Glycine max, Lupinus albus, Medicago sativa, Phaseolus vulgaris,
Pisum sativum, Psophocarpus tetragonolobus, Trifolium incarnatum,
Vicia faba, and Vigna angularis (Yoneyama et al., 2008).
A study showed that the expression of several secretory
proteins of Rhizophagus irregularis, an arbuscular mycorrhizal
fungus, was induced by strigolactone treatment (Tsuzuki
et al., 2016). Among these proteins, Strigolactone-Induced
Putative Secreted Protein 1 (SIS1) showed the highest induction
fold by both strigolactone treatment and Medicago truncatula
root symbiosis. SIS1 is important for colonization and the
formation of stunted arbuscules (Tsuzuki etal., 2016). erefore,
the strigolactone-induced is an essential protein for the
symbiosis (Tsuzuki et al., 2016).
Broomrapes, especially Orobanche crenata, are believed
to be the major parasitic weeds of legumes. The effects of
the parasitic weeds on legumes include local damage of the
plants and yield loss (Rubiales and Fernández-Aparicio, 2012).
The germination of Orobanche seeds is induced by
strigolatones (Yoneyama et al., 2008).
Ku et al. Legume Domestication and Secondary Metabolites
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Alkaloids and Saponins
Alkaloids and saponins are known for contributing to the bitter
taste of plants (Drewnowski and Gomez-Carneros, 2000). e
toxicity of alkaloids has been reported (Wink, 2013). Several
studies report that alkaloids and saponins are related to the
resistance to herbivores. For example, yellow lupin cultivar
with higher level of alkaloids in the leaves is more resistant
to aphid than the cultivar with lower level of alkaloids (Adhikari
et al., 2012). e removal of the bitter taste from modern
lupin cultivars has enabled them to be a protein source in
animal feed to reduce the dependence on soybean (Abraham
et al., 2019). However, “sweet” lupins are more susceptible to
predators (Muzquiz et al., 1994). Saponins have been thought
to be responsible for the resistance to insect attacks, as the
saponin preparation garden pea (Pisum sativum L.) resistant
to Azuki bean beetle (Callosobruchus chinensis L.) inhibited
the development of the beetle (Applebaum et al., 1969).
ALTERATIONS OF SECONDARY
METABOLITE PROFILES IN LEGUMES
DURING DOMESTICATION
Polyphenols and Carotenoids Determine
the Colors of Seeds and Flowers
e seed coat color is mainly determined by polyphenols such
as tannins (Heiser, 1988; Espinosa-Alonso et al., 2006). It is
common for the pigmentation patterns of domesticated crops
to be altered compared to their wild relatives. e loss of
pigment in the seed coat of cultivated P. v u l g a r i s is an obvious
example of the eects of domestication (McClean etal., 2018).
In a survey of 18 Lablab purpureus (L. purpureus) germplasms,
including wild, semi-domesticated, and cultivated accessions,
it was found that all the wild accessions have gray-brown and
mottled seed coat (Maass, 2006). However, cultivated accessions
display a spectrum of seed coat colors, including cream-white,
cream, tan, and black (Maass, 2006). Unlike the wild accessions,
some cultivated accessions do not have mottled seed coats
(Maass, 2006). Among 11 landraces and two cultivated accessions
of peanut (Arachis hypogaea L.), it was found that all the
cultivated accessions have a single seed coat color: tan (Husain
and Mallikarjuna, 2012), while the landraces are either red or
tan (Husain and Mallikarjuna, 2012). Some landraces even
have variegated seed coats (Husain and Mallikarjuna, 2012).
In another study, it was shown that cultivated peanut
(A. hypogaea) could have purple, brown, red, or white seed
coats and some have variegated seed coats (Bertioli et al.,
2011). In a survey of a soybean population consisting of 1,957
domesticated and 1,079 wild accessions, it was found that
almost all wild accessions have purple owers and black seed
coats (Jeong et al., 2019), whereas the domesticated soybean
accessions have more diverse seed coat colors, including colorless
(yellow or green seeds), brown, or black, and more diverse
oral colors, including white or purple (Jeong et al., 2019).
In another study on 110 cultivated, 130 landrace, and 62 wild
soybean accessions, it was reported that all cultivated accessions
have yellow seeds, and landrace accessions have yellow, green,
brown, or black seeds, while all the wild accessions have black
seeds (Wang et al., 2018). Similarly, the modern cultivated
pea cv. Cameor (P. s at i v u m ) has transparent seed coat while
the wild accession (P. s a t iv um subsp. elatius JI64) has pigmented
seed coat (Smýkal et al., 2014). In another study on cultivated
(Lens culinaris ssp. Culinaris) and wild lentils (Lens culinaris
ssp. orientalis, L. culinaris ssp. odemensis, L. culinaris ssp.
tomentosus, Lens nigricans, and Lens ervoides, Lens lamottei),
although wild accessions do not necessarily have darker seed
coats, wild accessions have more complexed patterns on the
seed coats (Singh etal., 2014). e seed coats of the cultivated
accessions have either no or dotted patterns (Singh etal., 2014).
However, many of the wild accessions have marbled pattern
on seed coats (Singh etal., 2014). For chickpea (C. arietinum),
the light color of the cultivated seeds is thought to
be non-existing in wild accessions (Penmetsa et al., 2016).
e seed coat color is related to the defense against herbivore.
It has been suggested that a black seed coat protects the seed
from night-time foragers (Porter, 2013).
Polyphenols also give rise to the colors of owers (Wiesner
et al., 2017). In cowpea, cultivated accessions have a wide
range of oral colors while most of the wild accessions have
only purple owers (Lo etal., 2018). Similarly, cultivated soybean
accessions have purple, white, or other colors of owers
(Sundaramoorthy etal., 2015; Jeong etal., 2019), whereas most
of the wild soybean accessions have only purple owers
(Sundaramoorthy et al., 2015). On the contrary, in common
bean, most of the cultivated accessions have only white owers
while the wild accessions have white, pink, or purple owers
(García etal., 1997). Cultivated lentils (L. culinaris ssp. Culinaris)
have white or purple owers but some wild lentils, L. culinaris
ssp. odemensis, L. culinaris ssp. tomentosus and Lentil ervoides,
have only purple owers (Singh etal., 2014). e white owers
of cultivated chickpea (C. arietinum) is thought to benon-existing
in wild accessions (Penmetsa et al., 2016). For pea, cultivated
peas (P. s a ti vum ) usually have white owers while purple owers
are found in wild peas (Hellens et al., 2010). e contrasting
ower colors contributed to the establishment of the Mendel’s Laws.
The Co-Evolution of Seed and Floral Colors With
Foragers and Pollinators
As discussed above, cultivated legumes usually have lighter seed
coat colors compared to the wild counterparts. During
domestication, light seed coat colors have been preferred by
farmers. e loss of color is associated with the loss of secondary
metabolites, such as tannins (Heiser, 1988). As mentioned before,
a dark seed coat may protect the seeds from night-time foragers
in the wild (Porter, 2013). However, the potential increase in
loss of sown seeds to wild animals may not be signicant as
farmers usually have measures to keep foragers away from crops.
Another example is the loss of bitter compounds, such as alkaloids
and saponins in domesticated legumes. e loss of such compounds
would have enhanced the loss of seeds due to foraging by
animals and is usually not advantageous for the survival of the
crops without the protection provided by farmers. erefore,
the loss of bitter compounds in domesticated legumes is also
Ku et al. Legume Domestication and Secondary Metabolites
Frontiers in Genetics | www.frontiersin.org 6 September 2020 | Volume 11 | Article 581357
known as a conscious selection by breeders during domestication.
In soybean, most of the elite cultivated soybean seeds are yellow.
It was found that the stay-green G gene is associated with green
seeds and it controls seed dormancy, but is lost in elite cultivated
soybean seeds (Wang etal., 2018). In the survey of 110 cultivated,
130 landrace, and 62 wild soybean accessions, it was found
that the G genotype is present in only 4% of the cultivated
accessions, 21% of the landraces while it is found in 100% of
the wild accessions (Wang et al., 2018).
It has been suggested that oral color has co-evolved with
pollinators such as birds and bees. Bees tend to be attracted
to yellow owers while birds tend to prefer red owers due
to their dierent visual sensitivities (Toon et al., 2014).
Bee-pollinated plants usually have yellow, white, or blue owers
while bird-pollinated plants usually have red owers (Toon
et al., 2014). e transition from bee-pollination to bird-
pollination of Australian egg-and-bacon pea is related to the
number of bird species in the geographical region where the
plants grow (Toon et al., 2014). e yellow color of the Lotus
ower, together with the orientation, size, petal morphology,
sucrose-dominant nectar composition, and scent of the ower,
was reported as a factor contributing to the transition to
pollination by birds (Cronk and Ojeda, 2008).
Carotenoid Level Is Related to Seed Dispersal
by Animals
Besides polyphenols, carotenoids also play a role in determining
tissue colors. During domestication, the protability of seeds
is a major concern for farmers. erefore, genotypes with
reduced seed dispersal, including through pod shattering and
seed dispersal by animals, were actively selected for by breeders
and farmers. In a study on the seeds of 10 legume genera:
Arachis (peanut), Cicer (chickpea), Glycine (soybean), Lathyrus
(vetch), Lens (lentil), Lupinus (lupin), Phaseolus (bean), Pisum
(pea), Vicia (fava bean), and Vig na (cowpea), drastic changes
in the levels and compositions of carotenoids in seeds were
found in domesticated cultivars compared to their wild
counterparts (Fernández-marín et al., 2014). An average of
48% reduction in carotenoids was found in the seeds of these
10 legumes. Besides, the compositions of carotenoids were
more complex in the wild species of Cicer, Glycine, Lathyrus,
Lens, Lupinus, and Vigna. In the study, neoxanthin, violaxanthin,
lutein epoxide, and antheraxanthin were only found in the
wild species but not the domesticated varieties. It was suggested
that seeds with lower carotenoid levels are less attractive to
seed dispersers (Fernández-marín et al., 2014). In contrast,
attracting seed dispersers has been suggested to bean adaptation
of wild legumes (Brǿnnvik and von Wettberg, 2019). It was
suggested that seed dispersal by birds is an important factor
contributing to the widespread of P. v u l g a r i s from Mexico to
South America (Brǿnnvik and von Wettberg, 2019).
Isoavones Are Unique to Legumes
Isoavones are a sub-class of avonoid uniquely found in
legumes. Soybean is a rich and common source of isoavones
for human consumption (Ku et al., 2020). In a study of seed
isoavone contents using 209 wild, 580 landrace, and 106
cultivated soybean accessions, it was found that landraces had
the highest average level of total seed isoavone, followed by
wild accessions and then cultivated accessions (Wang et al.,
2010). e higher average total seed isoavone content in
landraces compared to cultivated accessions was also reported
in another study using 927 landraces and 241 cultivars (Azam
etal., 2020). For individual isoavone contents, it was suggested
that high genistin and glycitin contents, with low daidzin levels,
were articially selected for. e signicantly lower daidzin
contents lead to the lower average total seed isoavone levels
in cultivated accessions compared to wild accessions (Wang
et al., 2010). ere are debates over the reasons behind the
articial selection of such seed isoavone traits in domesticated
legumes. Regarding seed nutrient content, a negative correlation
between the total isoavone level and the protein level has
been reported in seeds (Primomo et al., 2005; Morrison et al.,
2008; Liang etal., 2010; Smallwood etal., 2014), and a positive
correlation between total seed isoavone level and seed oil
level has also been reported (Morrison et al., 2008; Liang
et al., 2010). However, there has also been a report on the
negative correlation between total seed isoavone level and
seed oil level (Smallwood etal., 2014). e total seed isoavone
has also been correlated to yield (Primomo et al., 2005;
Smallwood et al., 2014; Zhang et al., 2014), as well as the
resistance against pathogens (Carter et al., 2018). When two
soybean cultivars, RCAT1004 and DH4202, which are resistant
and sensitive to cyst nematodes respectively, were grown in
a cyst nematode-infested environment, the resistant cultivar
had a higher seed isoavone level (Carter et al., 2018). A
putative QTL related to cyst nematode susceptibility was found
close to that related to total seed isoavone content (Carter
et al., 2018). During domestication, besides the deliberate
selection for reduced seed isoavone level to reduce the bitterness
of the seed, the isoavone level may also be unintentionally
selected together with other desirable traits, such as nutrient
composition, yield, and resistance to biotic stress.
Alkaloid and Saponin Contents Are
Related to Taste-Focused Breeding
e bitter taste of legume seeds tends to be eliminated during
domestication. For example, domesticated lupin cultivars are less
bitter than the wild relatives, which have signicantly higher levels
of alkaloids in their seeds. Modern lupin cultivars are referred
to as “sweet” lupins. In a survey of 20 sweet lupins and 29 bitter
lupins, the bitter taste of lupins was found to bepositively correlated
to the seed alkaloid content, with lupanine being the main alkaloid
(Muzquiz et al., 1994). Although seed saponin level has been
correlated to the bitterness of seeds in general (Mohan et al.,
2016), it may not be related to the bitterness of lupin seeds. In
a survey of the seed saponin contents in sweet vs. bitter lupins,
the level of saponin was undetectable in the seeds of both sweet
and bitter varieties of L. albus (Shim et al., 2003).
Saponin is also a contributing factor to the bitterness of
seeds (Okubo et al., 1992). It was found that many of the
wild ancestors of Vigna spp. are more resistant than
their cultivated counterparts to Callosobruchus chinensis or
Callosobruchus maculatus (Tomooka etal., 2000). It is possible
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that the drop in saponin contents when legumes became
domesticated is related to the loss of insect resistance capability
in cultivated species. Several wild chickpea accessions have
higher seed saponin levels than cultivated chickpea accessions
(Kaur etal., 2019). Several wild pigeonpea (Cajanus scarabaeoides)
accessions have higher seed saponin contents than the cultivated
pigeonpea accessions (Cajanus cajan; Sekhon et al., 2017).
However, cultivated pigeonpea accessions do not necessarily
have lower seed saponin contents than the wild accessions
(Sekhon et al., 2017). Seed saponin content is not the sole
factor leading to the insect resistance of legumes.
Besides total seed saponin content, individual saponin
components in legumes are also studied. Saponins can beclassied
into four groups: group A saponins, group B saponins, group E
saponins, and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one
(DDMP) saponins (Sawai and Saito, 2011; Krishnamurthy
etal., 2013). e aglycone form of group A saponins is named
soyasapogenol A, while that of DDMP saponins is named
soyasapogenol B. e basic structure of soyasapogenol A and
B is β-amyrin. Soyasapogenol A is a β-amyrin with a hydroxyl
group at C-21, C-22, and C-24, while soyasapogenol B has a
hydroxyl group at C-22 and C-24 only (Sawai and Saito, 2011).
DDMP saponins are relatively unstable and are oen degraded
into group B and group E saponins during food processing
(Sundaramoorthy et al., 2019). Among the various groups
of saponins, group A saponins, which have an acetylated
oligosaccharide chain attached to C-22 of soyasapogenol A, are
thought to be mostly responsible for the undesirable taste of
soybean seeds (Shiraiwa et al., 1991).
In a survey of saponin compositions among 800 cultivated
soybean accessions and 329 wild soybean accessions, it was
found that the saponin type Aa was predominant in cultivated
soybean accessions, while the saponin type AaBc was predominant
in wild soybean accessions (Tsukamoto etal., 1993). In another
survey of the total seed saponin levels in 17 wild and one
cultivated legumes, it was found that the total saponin level
was highest in Glycine soja (G. soja; wild soybean; Shim et al.,
2003). In a study of seed saponin composition of 3,025 G. soja
accessions, diverse compositions of seed saponins were found
among the accessions (Krishnamurthy et al., 2013). Moreover,
naturally occurring wild soybean mutants that lack group A
saponins were found (Krishnamurthy et al., 2013; Takahashi
etal., 2016; Rehman etal., 2018). Wild legumes do not necessarily
have higher seed saponin contents. Instead, the diverse genetic
backgrounds among wild legumes allow the discovery of novel
allelic forms for desirable seed saponin compositions.
Polyphenols and Strigolactones Are
Related to Biotic Interactions
Flavonoids are signaling molecules for legume-microbe interaction
(Abdel-lateif et al., 2012). In a test of nodulating capability of
Rhizobium japonicum (R. japonicum), it was found that all the
strains of R. japonicum in the test could nodulate cowpea,
sirato, and wild soybean (Heront and Pueppket, 1984). However,
nine out of the 11 strains could not form infection threads
with two of the three commercial soybean cultivars in the test
(Heront and Pueppket, 1984). In another study, aer inoculating
36 G. soja (wild soybean) accessions with R. japonicum, 20
formed normal nodules while 16 could not form nodules or
formed abnormal nodule-like structures (Pueppke et al., 1998).
It was hypothesized that the dierent nodulating phenotypes
were due to the dierent avonoid proles in the root exudates
(Pueppke et al., 1998). However, the avonoid proles of root
exudates are similar between the nodulating group and the
non-nodulating group (Pueppke et al., 1998). e avonoid
proles of root exudates were also compared between wild
soybean accessions and the cultivated soybean Peking (Pueppke
et al., 1998). Although many of the wild soybeans showed a
more complexed root exudate prole, a strong correlation
between the dierent root exudates and the nodulating phenotypes
was not found (Pueppke etal., 1998). e eects of domestication
on the avonoid proles in legume root exudates remain unclear.
On the other hand, the root polyphenol compositions of wild
lentil (Lens ervoides) and cultivated lentil (Lens culinaris) were
compared aer the infection of Aphanomyces euteiches, which
is a legume pathogen (Bazghaleh et al., 2018). e wild lentil
was more tolerant to A. euteiches than the cultivated lentil
pathogen (Bazghaleh et al., 2018). e wild lentil generally
had higher levels of polyphenols compared to the cultivated
lentil (Bazghaleh et al., 2018). Although the amount of legume
species and accessions is not enough to conclude the eect of
domestication on the root polyphenol compositions aer pathogen
infection, genotypic dierence exists between wild and cultivated
legumes and is associated with polyphenol accumulation in
roots under biotic stress.
Strigolactones are stimulants of seed germination (Brun
et al., 2018). e yield of faba bean (V. fab a ) is also limited
by parasitic weeds. Faba bean (V. f a b a ) germplasms resistant
to parasitic weeds, broomrape (Orobanche and Phelipanche
spp.) were found (Fernández-Aparicio etal., 2014). e resistant
germplasms have low or undetectable levels of strigolactones
in the root exudates at all plant ages (Fernández-Aparicio
etal., 2014). It was suggested that the screening of germplasms
with low strigalactone levels in root exudates is a strategy to
breed for weed resistant germplasms. Like faba bean (V. faba ),
most of the commercial pea (Pisum sativum L.) cultivars are
susceptible to the attack by crenate broompape (O. crenata
Forsk.), which is a parasitic weed of legumes (Pavan et al.,
2016). In a screen of O. crenata resistant pea germplasms, a
landrace pea germplasm was selected. Repeated self-pollination
of the landrace germplasm resulted in the O. crenata resistant
line ROR12 (Pavan etal., 2016), which exhibited several unique
characters: (1) compared to a O. crenata susceptible cultivar,
the root exudates of ROR12, which had a lower strigolactone
level, had a lower capability to stimulate the germination of
O. crenata seeds; (2) in the eld, the number of O. crenata
shoots per host plant of ROR12 was lower; and (3) the
emergence of O. crenata on ROR12 was delayed. It was proposed
that the resistance to O. crenata was related to the reduced
strigolactone level in the root exudates (Pavan et al., 2016).
Strigolactones are also involved in legume-microbe
interaction. e treatment of synthetic strigolactone (GR24)
to pea (Pisum sativum L.) roots enhanced the nodule number
on the roots due to Rhizobium leguminosarum bv. viciae
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(RLV248) inoculation (Foo and Davies, 2011). Mutant rms1
of pea (Pisum sativum L.) had undetectable levels of orobanchol
and orobanchyl acetate and a low level of fabacyl acetate in
the root exudates (Foo and Davies, 2011). Compared to the
wild type, rms1 mutant had less nodules on the roots aer
being inoculated with R. leguminosarum b v. viciae (RLV248;
Foo and Davies, 2011). Commercial legume germplasms usually
have lower levels of strigolactones in the root exudate
(Fernández-Aparicio et al., 2014; Pavan et al., 2016).
e low levels of strigolactones may result in the reduced
number of nodules on the roots. However, the nodulating
phenotype may not be of consideration during domestication
as the application of nitrogen fertilizer is a common practice
during domestication.
GENES THAT REGULATE THE DIFFERENT
SECONDARY METABOLITE-RELATED
TRAITS
Several methods are currently being employed to identify the
genes and mutations underlying legume domestication
phenotypes (Olsen and Wendel, 2013). In general, secondary
metabolites are present at higher levels in wild progenitors
than in the domesticated counterparts as a result of articial
selection (Nagl etal., 1997; Lindig-Cisneros etal., 2002; Gepts,
2014). e selection of cultivars based on ease of farming and
other commercial attributes may have occurred at the expense
of potentially benecial secondary metabolites. e reduction
in genetic diversity is one of the main impacts of domestication.
However, the genetic richness of wild populations can beused
to improve cultivated legumes. Traditional plant breeding is a
millenary process for the improvement and development of
new crop varieties. According to breeding objectives, new
legume varieties are produced by crossing parents with desired
traits and selecting among segregating progenies those individuals
with both high yield and the target trait. In this way, pest-
resistant varieties have been developed with genetic resistance
to pathogens (Lavaud etal., 2015). Traits related to pigmentation
and defense against pathogens or herbivores are characteristically
domestication-related traits governed by secondary metabolites.
Besides biosynthesis-related genes, transport-related genes are
also important. e roles of transporters, including ATP-binding
cassette (ABC) transporters and multidrug and toxic compound
extrusion (MATE) transporters in secondary metabolite secretion
and accumulation have been summarized in previous reviews
(Yazaki, 2005; Ku et al., 2020). In this section, examples of
genes and loci controlling secondary metabolite biosynthesis
and transport in legumes will be discussed.
Biosynthesis-Related Genes
Pigmentation-Related Traits
Polyphenols are the major determinants of tissue colors,
including the colors of seed coats of legumes, both by their
presence and their quantities (Espinosa-Alonso et al., 2006).
e major polyphenols responsible for seed coat color in
legumes are avonoids, such as anthocyanins, avonol glycosides,
and proanthocyanidins (condensed tannins). Flavonoid quantities
vary according to the seed developmental stages, genotypes,
and species. e biosynthetic pathway leading to the biosynthesis
of avonoids has been elucidated and is conserved among
seed-producing plants. Flavonoids and isoavonoids are derived
from the phenylpropanoid pathway (Dastmalchi and Dhaubhadel,
2014). Many genes in this pathway, including enzymes,
transporters, and regulatory factors, have been characterized.
e rst committed step is the formation of a bicyclic
tetrahydroxy chalcone (naringenin chalcone) catalyzed by a
chalcone synthase (CHS). Legumes produce an additional
trihydroxy chalcone (THC), isoliquiritigenin chalcone
(Dastmalchi and Dhaubhadel, 2014). is THC is the end
product of the coupled activities of CHS and the legume-
specic chalcone reductase (CHR). Compounds such as daidzein,
medicarpin, and glyceollin are derived from isoliquiritigenin.
Flavonoid production follows the conversion of naringenin
chalcone to (2S)-naringenin by chalcone isomerase (CHI).
Flavone 3-hydroxylase (F3H) catalyzes the hydroxylation of
(2S)-naringenin, eryodictyol, and pentahydroxyl avanones to
yield (2R,3R)-dihydrokaempferol, dihydroquercetin, and
dihydromyricetin, respectively (Tanaka et al., 2008). Flavonoid
3'-hydroxylase (F3'H) and avonoid 3',5'-hydroxylase (F3'5'H)
catalyze the hydroxylation of flavanones, flavanols, and
flavones, and determine the structures of flavonoids and
anthocyanins (Tanaka, 2006). Other enzymes in the pathway
include dihydroflavonol 4-reductase (DFR) and anthocyanidin
synthase (ANS). The biosynthesis pathway of flavonoids is
illustrated in Figure 1.
Pigmentation mechanisms have been studied in dierent
legumes. A transcriptomic analysis was performed to identify
the genes associated with seed coat color in peanut (A. hypogaea;
Wan et al., 2016). Lower proanthocyanidin and anthocyanin
contents were detected in a peanut mutant with a brown cracking
seed coat (pscb). Transcriptomic analyses revealed that the structural
genes of the phenylpropanoid biosynthetic pathway were
downregulated in the pscb mutant, while the genes related to
melanin production were upregulated at the late developmental
stages. is expression pattern was consistent with the higher
melanin content in the pscb mutant compared to the wild type.
Dierential expression analyses of RNA-seq data between the
wild type and pscb mutant revealed three candidate genes (c36498_
g1, c40902_g2, and c33560_g1) as being responsible for the seed
coat color trait. C33560_g1 encodes a R2R3-MYB transcription
factor. Its homologs in Arabidopsis and apple are associated with
the regulation of the phenylpropanoid biosynthesis pathway (Rowan
etal., 2009; Vimolmangkang etal., 2013). C36498_g1 and c40902_g2
encode a caeoyl-CoA O-methyltransferase and a kinesin-4-like
protein, respectively. Putative functions of the encoded proteins
were associated with cell wall organization.
Soybeans cultivated for the commercial market are either
completely yellow or have pigmentation restricted to the hilum
(Palmer etal., 2004). Wild soybeans accumulate avonoids and
anthocyanins within the entire epidermal layer of the seed coat,
giving them a black or brown color (Todd and Vodkin, 1993;
Song et al., 2016). Quantitative trait loci (QTL) governing
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seed coat color in soybean have been identied using genetic
and genomic analyses to elucidate the genetic changes that
resulted in this domestication trait (Todd and Vodkin, 1996;
Tuteja et al., 2004, 2009; Song et al., 2016). e I, R, and T
loci were found to be involved in the avonoid biosynthesis
pathway (Palmer et al., 2004; Yang et al., 2010). e I locus
on chromosome eight inhibits pigmentation of the seed coat.
ere are four alleles (I, ii, ik, and i) at the I locus where I
and ii are the two dominant forms (Song et al., 2016). e
presence of the I allele results in the absence of pigmentation
and a yellow seed coat at maturity. is allele contains an
inverted repeat of the CHS gene cluster. is structure triggers
posttranscriptional gene silencing (PTGS), which inhibits the
expression of CHS gene family members and their functions
in the avonoid biosynthesis pathway (Tuteja et al., 2004).
e ii allele inhibits pigmentation, resulting in a yellow seed
coat with a pigmented hilum (Palmer et al., 2004). Meanwhile,
the recessive ik and i alleles allow pigment production, with
the ik allele restringing pigments to the saddle and hilum
regions of the seed coat (Palmer et al., 2004). e R and T
loci determine the type and accumulation of pigments in the
seed coat (Buzzetl etal., 1987; Todd and Vodkin, 1993). Higher
avonoid and anthocyanin contents of seeds are currently of
great interest due to the antioxidant properties and avors of
these compounds. Recently, the wild soybean reference genome
of G. soja W05 was used to identify additional alleles of the
causal structural gene variation that controls soybean seed coat
pigmentation (Xie et al., 2019). e analysis of a seed coat
color QTL that overlaps with the known I locus showed that
the W05 reference genome possesses the same inverted repeat
of the CHS gene cluster as the domesticated soybean reference
genome, G. max (Williams 82). is indicates that additional
factors also played a role in causing the seed color changes
during domestication. A comparative genomic analysis of W05
against two domesticated soybeans (Wm82 and ZH13) revealed
the generation of a small interfering RNA (siRNA) from a
large structural rearrangement next to the CHS gene cluster
in Wm82 and ZH13. rough experimental validation, a subtilisin
promoter was shown to drive the expression of a chimeric
transcript that reads through a subtilisin gene fragment and
an anti-CHS1 gene region, resulting in PTGS and inhibits the
expression of CHS genes.
Flavonoids also contribute to oral pigmentation (Tanaka,
2006; Tanaka et al., 2008). Domesticated cowpea (Vigna
unguiculata L. Walp) shows phenotypic variation compared to
its wild relatives. Among the domestication traits, a wide range
of oral and seed coat colors can be found in the cultivated
cowpea. e wild variety shows purple owers and dark seed
pigmentation. Purple owers are the results of diacylated
delphinidin-based anthocyanins (Tanaka et al., 2008). A QTL
analysis of the determinants of oral color in cowpea was performed
in a biparental mapping population (wild × cultivated crosses;
FIGURE1 | Schematic representation of the avonoid biosynthetic pathway. Enzymes involved in the pathway are indicated in bold: chalcone synthase (CHS),
chalcone reductase (CHR), avone 3-hydroxylase (F3H), avonoid 3'-hydroxylase (F3'H), avonoid 3',5'-hydroxylase (F3'5'H), dihydroavonol 4-reductase (DFR), and
anthocyanidin synthase (ANS).
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FIGURE2 | Schematic representation of the pathway leading to the
synthesis of quinolizidine alkaloid compounds. Enzymes involved in the
pathway are indicated in bold: lysine decarboxylase (LDC), copper amine
oxidase (CuAO), (+)-epilupinine O-coumaroyltransferase (ECT), (+)-epilupinine
feruloyltransferase (EFT), (−)-lupinine O-coumaroyltransferase (LCT),
(−)-lupinine feruloyltransferase (LFT), (−)-13α-hydroxymultiorine transferase
(HMT), and (+)-13α-hydroxylupanine O-tigloyltransferas (HLT).
Lo et al., 2018). A single major QTL for oral color, CFcol7,
was mapped in a 64-cM region on chromosome Vu07 containing
254 annotated genes, among which a transcription factor,
Vigun07g110700, was identied as a homolog of Arabidopsis
AT4G09820.1 and Medicago truncatula (Mt) TT8, involved in
the regulation of avonoid biosynthesis (Nesi et al., 2000; Li
et al., 2016). In soybean, one QTL for oral pigmentation was
identied on linkage group G (Josie et al., 2007).
Defense-Related Traits
Toxic secondary metabolites in legumes confer resistance against
pathogens and herbivores. However, the accumulation of these
compounds in legume crops is not desirable for human
consumption or as animal feed since they impart a bitter taste
and could present acute toxicity if ingested in sucient quantities
(Daverio etal., 2014). Alkaloids are some of the main secondary
metabolites produced and stored by legumes with characteristic
toxicity (Wink, 2013). Examples are quinolizidine alkaloids (QAs)
produced by the genera Lupinus, Baptisia, ermopsis, Genista,
Cytisus, Echinosophora, and Sophora (Ohmiya et al., 1995). e
breeding of low-alkaloid (sweet) varieties changed the agronomic
roles of lupins from green manure and forage crops to grain
legumes with high protein and ber contents and health benets
(Sweetingham and Kingwell, 2008; Arnoldi et al., 2015). Four
species within the genus Lupinus have been domesticated and
are important legume crops: Lupinus angustifolius (narrow-leafed
lupin or blue lupin), L. albus (white lupin), Lupinus luteus (yellow
lupin), and Lupinus mutabilis (Andean lupin) (Gustafsson and
Gadd, 1965; Reinhard et al., 2006). QAs produced by lupins
include lupanine, angustifoline, lupinine, sparteine, multiorine,
and aphylline (Frick et al., 2017). e use of lupins for food
purposes depends on their QA levels and each species has a
characteristic alkaloid composition. Domestication has reduced
the amount of alkaloids in lupins, but it has also increased their
susceptibility to several aphid species (Philippi etal., 2015). QAs
are derived from the decarboxylation of L-lysine (Lys) by a lysine
decarboxylase (LDC, EC 4.1.1.18) to form cadaverine (Bunsupa
et al., 2012a,b), which is then converted to 5-aminopentanal via
oxidative deamination by a copper amine oxidase (CuAO, EC
1.4.3.22). 5-aminopentanal is spontaneously cyclized to a Δ1
piperideine Schi base formation (Leistner and Spenser, 1973;
Gupta et al., 1979; Golebiewski and Spenser, 1988; Bunsupa
et al., 2012b), which then undergoes further modications (e.g.,
oxygenation, dehydrogenation, hydroxylation, or esterication)
to produce a range of Lys-derived alkaloids, including lupinine,
sparteine, lupanine, and multiorane (Ohmiya etal., 1995; Bunsupa
et al., 2012b; Frick et al., 2017). QAs are stored in the form of
QA esters. In lupins, QA esters are converted from lupinine/
epilupinine and 13α-tigloyloxymultiorine/13α-tigloyloxylupanine
by two types of acetyltransferases (ATs): (+)-epilupinine/
(−)-lupinine O-coumaroyl/feruloyltransferase (ECT/EFT-LCT/
LFT) and (−)-13α-hydroxymultiorine/(+)-13α-hydroxylupanine
O-tigloyltransferase (HMT/HLT; EC 2.3.1.93), respectively (Saito
et al., 1992; Okada et al., 2005; Bunsupa et al., 2012a). e
biosynthesis pathway of QAs is illustrated in Figure2. An HMT/
HLT-type acetyltransferase was isolated and characterized at the
molecular level in L. albus (Okada et al., 2005) while an
acyltransferase-like gene, Lupinus angustifolius acyltransferase
(LaAT ), has been proposed to be involved in the QA biosynthetic
pathway (Bunsupa et al., 2011).
Domestication-related genetic modications resulting in
low-alkaloid phenotypes are generally results of naturally
occurring (spontaneous) mutations (Gustafsson and Gadd,
1965). e domestication of lupins led to the active selection
by farmers/breeders for sweet varieties which were low in
alkaloids. In the late 1920s, the rst low-alkaloid lines were
obtained from wild germplasms of L. luteus and L. angustifolius
(von Sengbusch, 1942). Subsequently, sweet types were also
obtained for L. albus and L. mutabilis in the 1930s (Taylor
etal., 2020). Several recessive low-alkaloid mutations have been
discovered in L. angustifolius: iucundus (iuc), esculentus (es),
depressus (depr), and tantalus (Swiecicki and Swiecicki, 1995;
Kurlovich, 2002; Taylor etal., 2020), among which, the iucundus
locus is the most prevalent allele in cultivars (Taylor et al.,
2020). Molecular mapping eorts have allowed researchers to
map the iucundus locus to a 746-kb region on chromosome
NLL-07 (Nelson et al., 2006, 2010; Hane et al., 2017). e
reference L. angustifolius genome also facilitated the identication
of markers linked to iucundus that are suitable for marker-
assisted selection (MAS). Specically, an allele marker, IucLi,
has been identied for the iucundus locus, and could be used
for MAS in wild × domesticated crosses in lupin breeding
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programs (Li et al., 2011). Recently, 12 candidate genes for
the alkaloid locus iucundus and the major QTLs associated
with total QA contents were identied using a transcriptomic
approach (Kroc etal., 2019b). e most promising candidate,
RAP2-7, encodes an ethylene-responsive transcription factor
(ERF) that co-segregated with the iucundus locus and is likely
to be involved in the regulation of QA biosynthesis in
L. angustifolius (Kroc et al., 2019a). Other candidate genes
include a 4-hydroxy-tetrahydrodipicolinate synthase (DHDPS)
involved in Lys biosynthesis as well as genes involved in plant
secondary metabolism (Kroc et al., 2019b).
Recessive low-alkaloid mutations in L. albus have also been
identied: pauper, mitis, reductus, exiguus, and nutricius
(Hackbarth, 1957; Troll, 1958; Porsche, 1964). As in the case
of L. angustifolius, one locus, pauper, is the most studied in
L. albus (Rychel and Książkiewicz, 2019). e Kiev
mutant × P27174 recombinant inbred lines (RILs) population
was used for the rst genetic map of L. albus where the pauper
locus was located on linkage group 11 (Phan et al., 2007).
Recently, a high-resolution map was developed to provide a
high-resolution QTL assay of the agronomic traits of L. albus
(Michał et al., 2017). e pauper locus was localized in the
linkage group ALB18 (Michał et al., 2017). e Lup021586
gene was identied in the region and showed 100% nucleotide
identity to La AT , the acyltransferase gene previously identied
in L. angustifolius (Bunsupa et al., 2011). LAGI01_35805, an
L. albus homolog of La AT that is highly similar to L. angustifolius
Lup021586 gene, has been proposed as a molecular marker
for the pauper locus (Rychel and Książkiewicz, 2019). Meanwhile,
four low-alkaloid alleles have been identied in L. luteus,
including dulcis, amoenus, liber, and v (von Sengbusch, 1942;
Gustafsson and Gadd, 1965). However, there is limited
information on the genetic basis for the low-alkaloid trait in
this species. Eorts to improve the genomic resources of L.
luteus are underway. e rst genetic map for L. luteus has
been recently released (Iqbal et al., 2019). A high-quality
reference genome will help to implement MAS and identify
loci responsible for the low-alkaloid content in L. luteus.
On the other hand, phytoalexins are a class of secondary
metabolites with antimicrobial activities that are synthesized de
novo aer biotic and abiotic stresses (Walton, 1997). Phytoalexin
biosynthesis can be induced by pathogens or a type of stress-
mimicking compounds called elicitors (Angelova et al., 2006),
and are produced by a range of crops including those in the
Fabaceae family (Ahuja etal., 2012). Phytoalexins produced by
the family Leguminosae comprise a variety of chemical compounds,
including avonoid phytoalexins derived from the shikimic acid
pathway. In species such as soybean, prenylated pterocarpans,
i.e., glyceollins, are synthesized in response to fungal pathogens
such as Phytophthora sojae and Macrophomina phaseolina (Lygin
et al., 2013). Soybean produces six forms of the isoavonoid
phytoalexin, glyceollin, where glyceollin I, glyceollin II, and
glyceollin III are the predominant isomers (Banks and Dewick,
1983), derived from the addition of a dimethylallyl chain to
(6aS,11aS)-3,9,6a-trihydroxypterocarpan (glycinol) at either C-4
or C-2 by prenyltransferases (PTs). Two isoavonoid PTs have
been identied in soybean: 4-dimethylallyltransferase (G4DT)
and glycinol 2-dimethylallyltransferase (G2DT; Akashi et al.,
2009; Yoneyama et al., 2016). Molecular characterization of PT
genes revealed that G4DT and G2DT are paralogs resulting
from a whole-genome duplication (Yoneyama et al., 2016). A
genome-wide analysis of PT genes in G. max Wm82 identied
77 PT-encoding genes with 11 putative isoavonoid-specic PTs
(Sukumaran etal., 2018). One of the candidate genes, GmPT01
(G2DT-2) was induced by P. s o j a e infection and AgNO3, which
mimics pathogen attack and lies in the QTL linked to P. s o j a e
resistance. It was suggested that GmPT01 is one of the genes
involved in the partial resistance and could be used in breeding
for increased fungal resistance. Other genes related to P. s o j a e
resistance include a CHS gene, GmCHR2A, located near a QTL
linked to P. s o j a e resistance (Sepiol et al., 2017). Additionally,
studies have shown that resistant and susceptible genotypes
dier in their timing of activating glyceollin biosynthesis
(Yoshikawa et al., 1978; Hahn et al., 1985). A rapid activation
of the biosynthetic pathway allows a high level of accumulation
of these low-molecular weight compounds and confers resistance
to pathogens. Soybean genotypes encoding the P. s oj a e resistance
gene, Rps1k, have shown a rapid activation of glyceollin
biosynthesis and higher resistance to the pathogen (Yoshikawa
et al., 1978; Hahn et al., 1985). Recently, a member of the
NAC (NAM/ATAF1/2/CUC2)-family of transcription factor (TF)
genes, GmNAC42-1, was identied using comparative
transcriptomics (Jahan et al., 2020). GmNAC42-1 binds the
promoter of G4DT and plays a role in the accumulation of
glyceollin I. However, additional TFs are expected to participate
in the regulation of glyceollin biosynthesis.
e phytoalexins in pea (P. s at i v um ) are pisatin and maackiain
(Ahuja et al., 2012). Pisatin, a 6α-hydroxyl-pterocarpan
phytoalexin, is the major phytoalexin in pea produced in response
to fungal infections by Nectria haematococca, Botrytis cinerea,
and Mycosphaerella pinodes (Van den Heuvel and Glazener,
1975; Shiraishi et al., 1978; Etebu and Osborn, 2010). Its
biosynthetic pathway has been partially characterized (Paiva
etal., 1994; DiCenzo and Vanetten, 2006; Kaimoyo and VanEtten,
2008; Celoy and VanEtten, 2014). Pisatin and maackiain are
synthetized via two chiral intermediates, (−)-7,2'-dihydroxy-
4',5'-methylenedioxyisoavanone [(−)-sophorol] and (−)-7,2'-
dihydroxy-4',5'-methylenedioxyisoavanol [(−)-DMDI; Preisig
et al., 1989; Akashi et al., 2006; DiCenzo and Vanetten, 2006].
Sophorol reductase (SOR) is responsible for the production of
sophorol, and it can be inactivated by RNA-mediated genetic
interference (RNAi) which inhibits the production of pisatin
in transgenic pea hairy roots (Kaimoyo and VanEtten, 2008).
e pathway diverges for pisatin production aer (−)-DMDI
formation. In the last step of the pathway, the methylation of
(+)-6α-hydroxymaackiain (6α-HMK) at the C-3 position by
6α-hydroxymaackiain methyltransferase (HMM2) results in the
formation of (+)-pisatin. (−)-DMDI is converted to (−)-maackiain
by hydroxisoavanol dehydratase (HILD). e biosynthesis
pathway of (+)-pisatin and (−)-maackiain is illustrated in
Figure3. M. pinodes causes ascochyta blight, the most important
foliar disease of eld pea, which responds by accumulating
pisatin (Shiraishi et al., 1978). Eorts have been made to
elucidate the QTLs associated with the disease resistance and
Ku et al. Legume Domestication and Secondary Metabolites
Frontiers in Genetics | www.frontiersin.org 12 September 2020 | Volume 11 | Article 581357
to facilitate the introgression of resistance into pea cultivars
(Wroth, 1999; Timmerman-Vaughan etal., 2004; Prioul-Gervais
et al., 2007; Fondevilla et al., 2011). However, only moderate
resistance has been reported with such eorts in pea cultivars
(Kra et al., 1998). Wild relatives present a high phytoalexin
diversity (Lindig-Cisneros et al., 2002). e genetic controls
for the resistance to M. pinodes were studied in a wild P. s a t i v u m
subsp. syriacum accession P665 (Fondevilla et al., 2008). Six
QTLs associated with M. pinodes resistance were detected in
linkage groups II, III, IV, and V (Timmerman-Vaughan et al.,
2004; Prioul-Gervais etal., 2007). Quantitative trait loci MpV.1
and MpII.1 were specic for seedlings under growth chamber
conditions and MpIII.3 and MpIV.1 for adult plant resistance
in eld conditions (Timmerman-Vaughan et al., 2004; Prioul-
Gervais et al., 2007). In contrast, QTLs MpIII.1 and MpIII.2
were detected both for seedling and eld resistance (Timmerman-
Vaughan et al., 2004; Prioul-Gervais et al., 2007). MpIII.2
overlaps with a QTL previously reported to be related to the
resistance against ascochyta blight complex Asc3.1 (Timmerman-
Vaughan etal., 2004; Prioul-Gervais et al., 2007). A resistance-
gene analog (RGA1.1) was identied in the vicinity of this
QTL using P. s a t iv u m populations (Timmerman-Vaughan etal.,
2004; Prioul-Gervais et al., 2007). QTLs associated with partial
resistance to the root rot-causing A. euteiches have also been
identied in pea, and would be useful for improving and
facilitating the existing recurrent selection-based breeding
program (Kra, 1988; Lewis and Gritton, 1992). Pilet-Nayel
et al. (2002) crossed susceptible lines with partially resistant
ones in order to map the QTLs associated with resistance
against A. euteiches. e genetic map revealed seven such
genomic regions and Aph1 located on the linkage group IVb
was the most promising. Other minor QTLs were also identied
in the 13 linkage groups obtained in the genetic mapping
(Pilet-Nayel et al., 2002). Meta-analyses of four RILs of pea
revealed 27 meta-Aphanomyces resistance QTLs, including 11
with high consistency across populations, locations, years, and
isolates (Hamon etal., 2013). Seven highly consistent genomic
regions were identied with the potential for use in MAS for
pea improvement. Resistance QTLs located in these seven
regions were further validated (Lavaud etal., 2015). Backcross-
assisted selection programs were used to generate near-isogenic
lines (NILs) carrying the resistance alleles of individual or
combined resistance QTLs. e eects of two major QTLs,
Ae-Ps4.5, and Ae-Ps7.6, were validated. e NILs carrying the
resistance alleles of these two QTLs showed the highest resistance
to A. euteiches strains. Several minor-eect QTLs were also
validated, including Ae-Ps2.2 and Ae-Ps5.1. Genome-wide analyses
further validated most of these resistance QTLs and detected
additional novel resistance loci (Desgroux etal., 2016). Putative
candidate genes in these loci were related to biotic stress responses.
Transporters
ATP-binding cassette transporters and multidrug and toxic
compound extrusion transporters play important roles in
the secretion and accumulation of secondary metabolites
(Yazaki, 2005; Ku et al., 2020). These transporters are
associated with microbe interaction and nutrient accumulation
of legumes (Sugiyama et al., 2007; Zhang et al., 2010;
Fondevilla et al., 2011; Li et al., 2016).
ABC Transporter
In soybean (G. max), an ABC transporter was reported to
be involved in the root secretion of genistein, which is an
important signaling molecule for mediating the symbiosis with
rhizobia (Sugiyama etal., 2007). In M. truncatula, two half-ABC
transporters, STR and STR2, are essential for arbuscule development
in arbuscular mycorrhizal symbiosis (Zhang et al., 2010). e
expression of the STR and STR2 genes was induced in cortical
FIGURE3 | Schematic representation of the pathway leading to the
synthesis of (+)-pisatin and (−)-maackiain. Enzymes involved in the pathway
are indicated in bold: isoavone reductase (IFR), sophorol reductase (SOR),
(+)-6α-hydroxymaackiain 3-O-methyltransferase (HMM2), and
hydroxisoavanol dehydratase (HILD). The steps to convert
(−)-7,2'-dihydroxy-4',5'-methylenedioxyisoavanol (DMDI) to
(+)-6α-hydroxymaackiain are unknown (dotted arrow).
Ku et al. Legume Domestication and Secondary Metabolites
Frontiers in Genetics | www.frontiersin.org 13 September 2020 | Volume 11 | Article 581357
cells containing arbuscules (Zhang etal., 2010). STR and STR2
dimerize to form a transporter, which is located in the peri-
arbuscular membrane and is important for the arbuscule
development and therefore the symbiosis (Zhang etal., 2010).
e str mutant and STR2-silenced transgenic roots exhibited
stunted arbuscules aer inoculating with Glomus versiforme
(Zhang et al., 2010). In pea, using microarray technology, an
ABC transporter was found to have a higher expression in P.
sativum ssp. syriacum accession P665, which is resistant to
Mycosphaerella pinodes, than the sensitive accession Messire
(Fondevilla et al., 2011).
MATE Transporter
Seeds of wild soybeans (G. soja) generally have higher antioxidant
contents than cultivated soybeans (G. max; Li et al., 2016).
Statistical analysis showed the high correlation among the levels
of seed total antioxidants, phenolics, and avonoids (Li et al.,
2016). Using RILs resulted from the cross between the wild
soybean W05 (G. soja) and the cultivated soybean C08 (G. max),
QTLs regulating the contents of antioxidants, phenolics, and
avonoids in soybean seeds were identied, which share a
common genomic region (Li etal., 2016). In the target genomic
region, three genes, GmMATE1, GmMATE2, and GmMATE4,
were predicted to encode MATE transporters (Li et al., 2016).
ese MATE genes are possible candidates for investigating the
basis behind the dierent seed antioxidant contents between
wild soybeans (G. soja) and cultivated soybeans (G. max).
MOLECULAR BREEDING AND
SECONDARY METABOLITE CONTENT
As covered in this review, legumes produce a diverse array
of secondary metabolites including a large subset of compounds
with biopharmaceutical/nutraceutical properties. e production
of these phytochemicals can be increase through crop
improvement using classical breeding to genetic approaches
(Jacob et al., 2016). Legumes with increased health-benecial
secondary metabolites are potential raw materials for producing
pharmaceutical products.
e genetic variability of legume species is fundamental to
identify parental lines to be used in breeding programs and
exploit legume secondary metabolites. Modern targeted breeding
programs use tools, such as quantitative trait loci, marked-assisted
selection, and genomics applications (Collard and Mackill, 2008;
Jacob et al., 2016). DNA-based molecular markers are used to
characterize genomic regions (insertions, deletions, mutations)
controlling a particular trait or gene to dierentiate individuals
for germplasm identication and characterization (Nadeem etal.,
2018). Molecular markers provide breeders with a valuable resource
to accelerate selection programs and mark complex traits, which
are inuenced by environmental factors or not observable at
early stages of plant development. Flavonoids have pharmacological
eects, such as antioxidants for human nutrition or anti-
inammatory eects among others. Also, nutritional value of
legumes can beenhanced by increasing avonoid content though
breeding selection (D’Amelia et al., 2018). In this case, molecular
markers have been used to study genetic variability in legumes
to obtain varieties with high total avonoid content. Genetic
heritability of avonoids is high and germplasms with dierent
avonoid content can lead to the identication of potential markers
to use in breeding (Caseys et al., 2015). Flavonoid content was
determined in 57 peanut accessions to evaluate the association
between molecular markers and avonoid content (Hou et al.,
2017). Four expressed sequence tag-simple sequence repeat
(EST-SSRs) markers were identied related to high avonoid
content in Chinese peanut germplasm. Functions of these markers
were analyzed and related to outer membrane protein porin,
heat-shock transcription factor, and lectins (Hou et al., 2017).
Further studies are required to conrm the functions of these
ESTs in avonoid synthesis in peanuts. In soybean, three novel
alleles were identied associated to avonoid hydroxylase genes,
F3'H and F3'5'H, related to pigmentation traits (Guo and Qiu,
2013). ese molecular markers were identied using a set of
gene-tagged markers based on the sequence variation of GmF3'H
and GmF3'5'H in dierent soybean accessions, including cultivars,
landraces, and wild soybeans (Guo and Qiu, 2013). Domestication
process does not appear to erode diversity since four GmF3'H
alleles were identied among cultivated soybeans, while G. soja
contained only the GmF3'H allele. In the case of GmF3'5'H, 92.2%
of wild soybean contained the GmF3'5'H-a allele, while three
GmF3'5'H alleles occurred among cultivated soybeans (Guo and
Qiu, 2013). In white clover (Trifolium repens), diversity array
technology (DArT) and microsatellite markers were used to discover
marker-trait associations for avonoid accumulation and biomass
(Ballizany et al., 2016). Signicant associations to concentrations
of avonols quercetin, kaempferol, and Quercetin:Kaempferol ratio
were found to markers on linkage group 1–2. Additionally, the
study revealed deleterious alleles in an elite cultivar indicating
that genetic variability from wild germplasm could be used for
white clover improvement (Ballizany et al., 2016).
ENGINEERING SECONDARY
METABOLITE CONTENTS IN LEGUMES
In addition to breeding programs to improve domesticated
varieties and broaden the gene pool of cultivars, secondary
metabolite contents can also bemodied through plant metabolic
engineering (DellaPenna, 2001). e identication of genes
involved in the biosynthesis pathways of diverse secondary
metabolites has helped to drive strategies to optimize the
production of target compounds. Increased production of target
metabolites can beachieved by altering the primary or secondary
metabolism of an organism, for example, through the
overexpression of genes in biosynthetic pathways or by knocking
out gene expressions and hence the enzymatic activities of
competing pathways. In soybean, the manipulation of the (iso)
avonoid pathway and its eect on the resistance to P. s o j a e
has been studied (Cheng et al., 2015; Chen et al., 2018; Zhou
et al., 2018). GmIFR, encoding an isoavone reductase (IFR),
was identied and overexpressed in soybean (Cheng et al.,
2015). IFR catalyzes an intermediate step in the biosynthesis
of glyceollins (Graham etal., 1990) and its constitutive expression
Ku et al. Legume Domestication and Secondary Metabolites
Frontiers in Genetics | www.frontiersin.org 14 September 2020 | Volume 11 | Article 581357
in transgenic soybean plants enhances the resistance to P. s o j a e ,
along with higher glyceollin contents. Similar eects on pathogen
resistance were obtained by the overexpression of coenzyme
A ligase (GmPI4L) in transgenic soybean plants (Chen et al.,
2018). Further attempts to elucidate enzymes/genes responsible
for the resistance to pathogens include the overexpression of
a chalcone isomerase, GmCHI1A, in soybean hairy roots, which
enhanced daidzein accumulation and resistance to P. s o j a e
strain P6497R compared to the control (Zhou et al., 2018).
In alfalfa, nutritional value was increased by engineering genistein
glucoside production (Deavours and Dixon, 2005). A transgenic
alfalfa was developed by constitutively expressing an isoavone
synthase, MtIFS1, from M. truncatula. However, in the MtIFS1-
expressing transgenic alfalfa, isoavonoid production and
accumulation was tissue-specic and aected by environmental
factors such as UV-B and the disease-causing pathogen, Phoma
medicaginis (Deavours and Dixon, 2005). RNAi-mediated gene
silencing of isoavone reductase, SOR, and hydroxymaackiain-
3-O-methyltransferase in pea (P. s a t i v u m ) allowed the
identication of DMDI, an intermediary in the production of
pisatin and maackiain (Kaimoyo and VanEtten, 2008). Other
viable strategies of engineering secondary metabolite pathways
include biosynthesis in microorganisms and modulation of
gene expressions through manipulating the expressions of
transcription factors (Du et al., 2010). Recently, genome-scale
models have been used to represent the metabolic capabilities
of legumes, including alfalfa and soybean (Pfau et al., 2018;
Moreira et al., 2019). is approach allows the integration of
dierent kinds of omics data to get new insights into plant-
microbe interactions (diCenzo et al., 2016; Pfau et al., 2018;
Contador et al., 2020). Models of plant metabolic pathways
could also be used in the design of optimal-use biosynthesis
pathways of secondary metabolites.
CONCLUSION
Domestication generally results in the reduction in secondary
metabolites, which are oen related to the bitter taste of seeds
and the resistance of plants to biotic stresses. e phenomenon
is consistent with the reported decrease in crop biodiversity
due to domestication (Food and Agricultural Organization of
the United Nations, 2010). Having numerous health-benecial
secondary metabolites, legumes have the great potential to
be employed as the sources of bioactive compounds for
pharmaceutical use. On the other hand, besides abiotic stresses,
the changing climate may also bring forth unpredictable biotic
stresses such as insect infestations. From these perspectives,
it is important to retain the biodiversity of legumes in order
to maintain a healthy gene pool to produce new cultivars that
can respond to future changes in their environments.
Understanding the genes that govern the benecial secondary
metabolite compositions in legumes will facilitate the use of
wild legumes in breeding programs or metabolic engineering
to promote crop diversity, as well as to produce legumes with
favorable secondary metabolite proles.
AUTHOR CONTRIBUTIONS
H-ML planned and coordinated the writing. Y-SK put together
the rst complete dra and prepared the table. CC drew
Figures 1, 2. M-SN prepared the table and drew Figure 3.
All authors contributed to the search of literature and writings.
All authors contributed to the article and approved the
submitted version.
FUNDING
is work was supported by grants from the Hong Kong
Research Grants Council General Research Fund (14143916)
and Area of Excellence Scheme (AoE/M-403/16).
ACKNOWLEDGMENTS
J. Chu copy-edited this manuscript.
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