**2. Definitions of tolerance and resistance**

Generally, herbicide has very beneficial effects on agricultural production worldwide [1]. Herbicides are often the most reliable and economical option available to control weeds [2, 3]. The availability of herbicide has allowed that researchers modify plant height and transform plants for increased performance [4]. Efficiency and cost-effectiveness of herbicides has led to positive impact on the agricultural production systems in the developed countries [5]. Herbicide tolerance and herbicide resistance are two very important concepts that should be carefully considered. Standard definitions of the herbicide "tolerance" and "resistance" based on the crop and weed biology were established by the Weed Science Society of America (WSSA) in 1998. According to the definitions of the WSSA, tolerance is the inborn capacity of plant groups to survive and recreate after herbicide treatment. This infers there was no election or genetic manipulation to make the plant tolerant; it is naturally tolerant. Resistance is "the acquired capacity of a plant to survive and propagate after introduction to a dosage of herbicide typically deadly to the wild sort. Resistance may be innately happening or initiated by such strategies as genetic engineering or election of variations created by tissue culture or mutagenesis [6].

#### **3. Herbicide resistance mechanisms**

Fundamentally, two types of mechanisms are involved in resistance. Target-site resistance (TSR) is caused by changes in the tridimensional structure of the herbicide target protein that decreases herbicide binding, or by increased activity of the target protein. TSR is conferred by gene mutations in target enzymes such as 5-enolpyruvylshikimate-3-phosphate synthase, which is reported in many resistant weed species [7–9]. Non-target-site resistance (NTSR) is endowed by any mechanism not belonging to TSR, e.g., reduction in herbicide uptake or translocation in the plant, or enhanced herbicide detoxification [8, 10]. Mutations endowing herbicide resistance can be classified into two types. The first type is structural changes in a DNA sequence encoding a protein, i.e., structural mutations. Structural mutations endowing herbicide resistance are expected to cause a structural modification in the tridimensional structure of a protein that will lead to a decrease in the efficacy of an herbicide. For example, mutations conferring an amino acid substitution at the herbicide-binding site of a target protein can decrease the affinity of the herbicide for the target protein (TSR). Alternatively, mutations at the active site of a metabolic enzyme or a transporter protein can improve the activity of these proteins in herbicide degradation or compartmentation away from its site of action, respectively (NTSR). In the case of structural changes in DNA sequence, seeking the cause for resistance means identifying and being able to detect the relevant structural mutations in the DNA of resistant plants. The second type of mutations associated with herbicide resistance results in a difference in the expression of one or several genes in resistant plants compared to sensitive plants, i.e., regulatory mutations [11, 12]. These mutations are changes in a DNA sequence that can cause an increase in the expression of the herbicide target protein that compensates for the herbicide inhibitory action (TSR), or a variation in the expression of herbicide-metabolizing enzyme(s) or of transporter proteins that will lead to an increase in herbicide degradation or compartmentation away from its site of action, respectively (NTSR) [13]. Non-target-site resistance compared with target-site resistance is less investigated especially in broadleaf weed species. Non-target-site resistance may cause weeds evolve unforeseeable resistance to diverse herbicides of different modes of action [14].

#### **3.1. Target-site resistance**

one or several weed species. In spite of some concerns about weed resistance to herbicides, only a logical approach integrates all common strategies to inhabit herbicide resistance in

Although development of resistance in weeds is an undesirable phenomenon, herbicide tolerance in crops is favorable. If the principle crop is not always tolerant to the herbicide, the herbicide will either decrease the productiveness of the primary crop or kill it. If the herbicide is not strong enough, it could allow the proliferation of weeds within the crop field thus affecting the productiveness of the primary crop. It is therefore desirable to produce crops that are tolerant to herbicides. The important objectives of this chapter are to clearly explain the important biochemical and molecular reasons of herbicide resistance in weeds, and and at the

Generally, herbicide has very beneficial effects on agricultural production worldwide [1]. Herbicides are often the most reliable and economical option available to control weeds [2, 3]. The availability of herbicide has allowed that researchers modify plant height and transform plants for increased performance [4]. Efficiency and cost-effectiveness of herbicides has led to positive impact on the agricultural production systems in the developed countries [5]. Herbicide tolerance and herbicide resistance are two very important concepts that should be carefully considered. Standard definitions of the herbicide "tolerance" and "resistance" based on the crop and weed biology were established by the Weed Science Society of America (WSSA) in 1998. According to the definitions of the WSSA, tolerance is the inborn capacity of plant groups to survive and recreate after herbicide treatment. This infers there was no election or genetic manipulation to make the plant tolerant; it is naturally tolerant. Resistance is "the acquired capacity of a plant to survive and propagate after introduction to a dosage of herbicide typically deadly to the wild sort. Resistance may be innately happening or initiated by such strategies as genetic engineering or election of

Fundamentally, two types of mechanisms are involved in resistance. Target-site resistance (TSR) is caused by changes in the tridimensional structure of the herbicide target protein that decreases herbicide binding, or by increased activity of the target protein. TSR is conferred by gene mutations in target enzymes such as 5-enolpyruvylshikimate-3-phosphate synthase, which is reported in many resistant weed species [7–9]. Non-target-site resistance (NTSR) is endowed by any mechanism not belonging to TSR, e.g., reduction in herbicide uptake or translocation in the plant, or enhanced herbicide detoxification [8, 10]. Mutations endowing herbicide resistance can be classified into two types. The first type is structural changes in a

weeds because the Human population is ever increasing.

102 Herbicide Resistance in Weeds and Crops

same time investigate the methods for the production of HR crops.

**2. Definitions of tolerance and resistance**

variations created by tissue culture or mutagenesis [6].

**3. Herbicide resistance mechanisms**

#### *3.1.1. Resistance to protoporphyrinogen IX oxidase-inhibiting herbicides*

Protoporphyrinogen oxidase (Protox), the target site of the diphenylether herbicides, catalyzes the conversion of protoporphyrinogen to protoporphyrin IX in tetrapyrrole biosynthesis. Several herbicides including the diphenylethers and oxidiazoles inhibit PPO. Inhibition of Protox leads to the production of large quantities of free protoporphyrin IX in the cytoplasm, which causes photodynamic damage in the presence of light and oxygen [15]. Results of investigations with a resistant *Amaranthus tuberculatus* biotype have showed an unprecedented and unanticipated mutation in which resistance is endowed by an amino acid deletion. Presumably, chloroplastic and mitochondrial protoporphyrinogen oxidase encodes by the PPX2L gene in resistant *Amaranthus tuberculatus*, there is the lack of a 3-bp codon, bringing an elimination of glycine at position 210 [16]. It is the just reportage card of codon/amino acid omission presenting resistance to herbicide. The Gly-210 elimination in the protoporphyrinogen oxidase gene confers extremely rate resistance to protoporphyrinogen oxidase herbicides by minimal impact on the natural inclination of protoporphyrinogen oxidase for its substrate protogen; however, the omission causes 10-fold lower protoporphyrinogen oxidase activity toward the ferocious sort [17]. However, resistance to Protox inhibitors has been selected for cell cultures [18] and has been generated in transgenic plants expressing heterologous Protox genes [15]. For example, a Protox Val389 to meet substitution endowed resistance in a selected *Chlamydomonas reinhardtii* line [19]. It has been proposed that the introduced resistant forms of Protox would need to replace rather than simply supplying the endogenous plant enzyme in order to avoid production of the toxic oxygen species following herbicide treatment [15, 20]. An obvious question is whether Gly-210 substitution, rather than deletion, would endow resistance. Modeling demonstrated that substitutions at Gly-210 provide either little or no resistance, or greatly decrease PPO functionality [56]. The necessity for contemporary absence of three nucleotides in the encoding succession of the focus gene, in addition to the duplex focusing of the gene result should chloroplasts and mitochondria, ought to restrict the development about this omission resistance mechanism, however it has been demonstrated in a further four resistant *A. tuberculatus* societies [21].

#### *3.1.2. Resistance to tubulin assembly inhibiting herbicides*

Both target-site resistance and non-target-site resistance to tubulin herbicides exist [22]. Target-site-based resistance to dinitroaniline herbicides has evolved in several species, such as *Setaria viridis* and *Eleusine indica*. Dinitroaniline and other tubulin-inhibiting herbicides have been used for several decades, and evolved resistance has been reported in some weed species (only 12 weed species) [23]. The mode of action of this group of herbicides is to bind to plant tubulin dimers and disrupting microtubule growth [24, 25]. In fact, these herbicides inhibit cell division by binding to the tubulin monomers, preventing their polymerization and spindle fiber formation [24]. Microtubules are polymers of α- and β-tubulin dimers and are involved in many essential cellular processes, including mitosis, cytokinesis, and vesicular transport [23]. Several possible resistance mechanisms have been proposed, including microtubule hyperstabilization and posttranslational modification [26, 27], but decisive document for these is still wanting. However, witness is beginning to stack up for target-site mutations. Analysis of resistant *Eleusine indica* biotypes has shown that a Thr239 to Ile mutation in a a-tubulin gene endows a high level of resistance, provided a Met268 to Thr mutation confers a lower or intermediate level of resistance [28, 29]. The Thr239 to Ile mutation conferred resistance to oryzalin, pendimethalin, and amiprophos-methyl, but not to pronamide in transgenic tobacco [30]. Similarly, Lys350 to Glu or Met mutations in a b-tubulin gene conferred resistance to colchicine (which also inhibits cell division) in *Chlamydomonas reinhardtii* [31]. However, the latter mutations have not been reported in any higher plant resistant to dinitroaniline herbicides [15].

#### *3.1.3. Resistance to 5-enolpyruvylshikimate-3-phosphate synthase inhibitors*

Glyphosate, a widely used nonselective herbicide, inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), a key enzyme in the biosynthesis of the aromatic amino acids phenylalanine and tyrosine [15]. Glyphosate inhibits potently the chloroplast enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which catalyzes the reaction of shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP) to form 5-enolpyruvylshikimate-3-phosphate (EPSP). Glyphosate blockage of EPSPS activity interrupts the shikimate pathway and prevents aromatic amino acid product, ultimately causing plant death [32].

A major factor accelerating the evolution of glyphosate-resistant weeds has been the advent of transgenic glyphosate-resistant crops, such as soybean, maize, cotton, and canola. In these crops, glyphosate has replaced almost all other herbicides or other means of achieving weed control. From an evolutionary viewpoint, this singular reliance on glyphosate is an intense selection for any glyphosate-resistance genes [33, 9]. A serine substitution at Pro-106 (Pro-106-Ser) in an extremely conserved district of the EPSPS gene creates target-site glyphosate resistance, which was first observed in an *Eleusine indica* biotype [34, 35]. After that, as a first report, in glyphosate-resistant *E. indica* and *Lolium* populations have been first detected threonine and alanine substitutions at Pro-106 [36, 37]. Pro-106 (Pro-106-Ser) amino acid substitutions have been recognized in *E. indica* and also *Lolium* populations around the globe. These Pro-106 substitutions confer only a modest degree of glyphosate resistance [38].

Some researchers suggest that the resistant population of *Lolium rigidum* presents three different mechanisms of resistance to glyphosate, namely reduced absorption, reduced mobility in the plants, and a mutation in the gene coding for the enzyme targeted by glyphosate [39]. The crystal structure of *Escherichia coli* EPSPS and molecular modeling displays that glyphosate barricades EPSPS by engrossing the PEP binding site [40, 41]. Based on results of a decisive study on *E. coli* EPSPS Pro-106 substitutions and the crystal structure of EPSPS-S3P-glyphosate, it was found that a little restricted of the glyphosate/PEP binding site hole is created by Pro-106 substitutions, which maintains EPSPS functionality but confers glyphosate resistance [40]. In comparison, high-level glyphosate resistance is conferred by substitutions at Gly-101 or Thr-102, which decreases the content of the glyphosate/PEP binding and also this significantly decreases dependence for PEP [42]. Therefore, the protecting of EPSPS functionality may be very scarce in mutations, empowering both glyphosate and PEP binding [43].

It was shown that more than 40-fold EPSPS overexpress as a result of up to 100-fold EPSPS gene amplification. There are some evidences that proofed this fact in highly glyphosateresistant *Amaranthus palmeri* biotypes several years ago. This inheritable EPSPS gene amplification can affect the expression level and glyphosate resistance segregating in F2 generation plants [44]. Nowadays, some laboratory attempts is doing to protect this kind of field-evolved resistance by selection of glyphosate-resistant cell lines from several plant species with EPSPS gene amplification. For example, it was shown a three-fold increase in basal EPSPS mRNA and enzyme activity in glyphosate-resistant *L. rigidum*, and a supplementary higher EPSPS expression in some glyphosate-resistant *Conyza* biotypes. However, in these given species, glyphosate translocation decrease considers as the most important resistance mechanism [45, 46]. Breeders showed although EPSPS relative copy number in nuclear genome can positively influence EPSPS mRNA level, EPSPS protein amount and activity female parents have major role than male parents in transformation of resistance inheritance [47].

Multiple herbicide resistance evolves various heterologous resistance mechanisms enciphered by particular resistance genes that coexist at the individual and/or population level, conferring resistance to several herbicides with different modes of action. Given its significance in modern agriculture, the most serious multiple herbicide resistance scenarios are those involving glyphosate [48].

#### *3.1.4. Resistance to ACCase-inhibiting herbicides*

An obvious question is whether Gly-210 substitution, rather than deletion, would endow resistance. Modeling demonstrated that substitutions at Gly-210 provide either little or no resistance, or greatly decrease PPO functionality [56]. The necessity for contemporary absence of three nucleotides in the encoding succession of the focus gene, in addition to the duplex focusing of the gene result should chloroplasts and mitochondria, ought to restrict the development about this omission resistance mechanism, however it has been demonstrated in a

Both target-site resistance and non-target-site resistance to tubulin herbicides exist [22]. Target-site-based resistance to dinitroaniline herbicides has evolved in several species, such as *Setaria viridis* and *Eleusine indica*. Dinitroaniline and other tubulin-inhibiting herbicides have been used for several decades, and evolved resistance has been reported in some weed species (only 12 weed species) [23]. The mode of action of this group of herbicides is to bind to plant tubulin dimers and disrupting microtubule growth [24, 25]. In fact, these herbicides inhibit cell division by binding to the tubulin monomers, preventing their polymerization and spindle fiber formation [24]. Microtubules are polymers of α- and β-tubulin dimers and are involved in many essential cellular processes, including mitosis, cytokinesis, and vesicular transport [23]. Several possible resistance mechanisms have been proposed, including microtubule hyperstabilization and posttranslational modification [26, 27], but decisive document for these is still wanting. However, witness is beginning to stack up for target-site mutations. Analysis of resistant *Eleusine indica* biotypes has shown that a Thr239 to Ile mutation in a a-tubulin gene endows a high level of resistance, provided a Met268 to Thr mutation confers a lower or intermediate level of resistance [28, 29]. The Thr239 to Ile mutation conferred resistance to oryzalin, pendimethalin, and amiprophos-methyl, but not to pronamide in transgenic tobacco [30]. Similarly, Lys350 to Glu or Met mutations in a b-tubulin gene conferred resistance to colchicine (which also inhibits cell division) in *Chlamydomonas reinhardtii* [31]. However, the latter mutations have not been reported in any higher plant resistant to dini-

further four resistant *A. tuberculatus* societies [21].

104 Herbicide Resistance in Weeds and Crops

troaniline herbicides [15].

*3.1.2. Resistance to tubulin assembly inhibiting herbicides*

*3.1.3. Resistance to 5-enolpyruvylshikimate-3-phosphate synthase inhibitors*

matic amino acid product, ultimately causing plant death [32].

Glyphosate, a widely used nonselective herbicide, inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), a key enzyme in the biosynthesis of the aromatic amino acids phenylalanine and tyrosine [15]. Glyphosate inhibits potently the chloroplast enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which catalyzes the reaction of shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP) to form 5-enolpyruvylshikimate-3-phosphate (EPSP). Glyphosate blockage of EPSPS activity interrupts the shikimate pathway and prevents aro-

A major factor accelerating the evolution of glyphosate-resistant weeds has been the advent of transgenic glyphosate-resistant crops, such as soybean, maize, cotton, and canola. In these crops, glyphosate has replaced almost all other herbicides or other means of achieving weed control. From an evolutionary viewpoint, this singular reliance on glyphosate is an intense

The aryloxyphenoxypropionate (AOPP) and cyclohexanedione (CHD) herbicides inhibit acetyl-CoA carboxylase (ACCase) [49, 50]. Two types of ACCase have been identified: the heteromeric prokaryotic ACCase is composed of multiple subunits, whereas the homomeric eukaryotic ACCase is a large multidomain protein. Thus, most dicot species tolerate ACCaseinhibiting herbicides well, but most grass species are susceptible, meaning that ACCase herbicides control only grass weed species [51]. Multiple forms of eukaryotic ACCase are present in some grasses, which differ in herbicide sensitivity [52]. This is the primary basis for selectivity of these herbicides between grasses and dicots. Some grass species, including some cereal crops, are tolerant of these herbicides based on their ability to metabolize the herbicides to inactive compounds [53]. In addition, some grasses are tolerant due to an insensitive form of ACCase [54, 55].

Hedgehog dogtail (*Cynosurus echinatus*) is an annual grass, native to Europe, additionally broadly conveyed in North and South America, South Africa, and Australia. Two hedgehog dogtail biotypes, one diclofop-methyl (DM) safe and one DM vulnerable, were examined in detail for exploratory measurements reaction resistance components. The digestion system of 14CDM, D-corrosive, and D-conjugate metabolites were recognized by thin-layer chromatography. The acetyl-CoA carboxylase *in vitro* tests demonstrated that the objective site was exceptionally touchy to aryloxyphenoxy propanoate, cyclohexanedione, and phenylpyrazoline herbicides in the *Cenchrus echinatus* susceptible biotype, provided the resistant biotype was coldhearted to the already specified herbicides. DNA sequencing concentrates affirmed that *Cenchrus echinatus* cross-imperviousness to acetyl-CoA carboxylase inhibitors has been presented by particular acetyl-CoA carboxylase two-fold point transformations Ile-2041-Asn and Cys-2088-Arg [48].

The results of enzyme inhibition studies suggest several distinct altered forms of ACCase associated with different levels of resistance to various ACCase inhibitors [56]. Mostly, resistance to aryloxyphenoxy propanoate and cyclohexanedione herbicides is owing to a mutation in the objective enzyme, making it lesser susceptible to blockage by these herbicides. The results of enzyme deterrence investigates propose some different modified figures of acetyl CoA carboxylase correlated with various measures of resistance to distinct acetyl CoA carboxylase inhibitors. In contrast, a second biotype was very resistant to sethoxydim (R/S I50 ratio of 420), but had only a low level of resistance to other AOPP and CHD herbicides [57]. A similar pattern was observed in a *Setaria faberi* biotype from Iowa and in a sethoxydimresistant corn line selected in tissue culture [58, 57]. A third pattern of resistance, conferring high-level resistance to fluazifop and lower levels of resistance to other AOPP and CHDs, has been found in a biotype of *Eleusine indica* from Malaysia [59], a *Lolium rigidum* biotype from Australia [60]. In a fourth category, some biotypes are resistant to AOPP herbicides but not to CHDs. These include *L. rigidum* biotype a VLR69 from Australia [61], a *Lolium multiyorum* biotype from Oregon, the USA [62], and *Avena fatua* biotype UM33 from Manitoba, Canada [63]. Similar groupings of resistant biotypes have been proposed in Ref. [64] according to entire plant cross-resistance templates to aryloxyphenoxy propanoate and cyclohexanedione herbicides in *Avena fatua* biotypes from Canada. Because of the two different acetyl CoA carboxylase genes in the weed grasses, this plant family encodes both cytosolic and plastidic figures of the acetyl CoA carboxylase. The target form of acetyl CoA carboxylase for aryloxyphenoxy propanoate and cyclohexanedione herbicides is the plastidic form, and in fact, this form of acetyl CoA carboxylase is modified in resistant weed biotypes [65]. Generally, the different patterns of resistance may be endowed by separate mutations in the gene for plastidic ACCase. Some reports indicate that at least one of the mutations is located in the carboxyltransferase region, toward the C terminal end of plastidic ACCase [66, 67]. Further molecular analysis is required to confirm the identity of this and other mutations responsible for resistance to these herbicides [15].

#### *3.1.5. Resistance to AHAS (ALS)-inhibiting herbicides*

eukaryotic ACCase is a large multidomain protein. Thus, most dicot species tolerate ACCaseinhibiting herbicides well, but most grass species are susceptible, meaning that ACCase herbicides control only grass weed species [51]. Multiple forms of eukaryotic ACCase are present in some grasses, which differ in herbicide sensitivity [52]. This is the primary basis for selectivity of these herbicides between grasses and dicots. Some grass species, including some cereal crops, are tolerant of these herbicides based on their ability to metabolize the herbicides to inactive compounds [53]. In addition, some grasses are tolerant due to an insensitive form

Hedgehog dogtail (*Cynosurus echinatus*) is an annual grass, native to Europe, additionally broadly conveyed in North and South America, South Africa, and Australia. Two hedgehog dogtail biotypes, one diclofop-methyl (DM) safe and one DM vulnerable, were examined in detail for exploratory measurements reaction resistance components. The digestion system of 14CDM, D-corrosive, and D-conjugate metabolites were recognized by thin-layer chromatography. The acetyl-CoA carboxylase *in vitro* tests demonstrated that the objective site was exceptionally touchy to aryloxyphenoxy propanoate, cyclohexanedione, and phenylpyrazoline herbicides in the *Cenchrus echinatus* susceptible biotype, provided the resistant biotype was coldhearted to the already specified herbicides. DNA sequencing concentrates affirmed that *Cenchrus echinatus* cross-imperviousness to acetyl-CoA carboxylase inhibitors has been presented by particular acetyl-CoA carboxylase two-fold point transformations Ile-2041-Asn

The results of enzyme inhibition studies suggest several distinct altered forms of ACCase associated with different levels of resistance to various ACCase inhibitors [56]. Mostly, resistance to aryloxyphenoxy propanoate and cyclohexanedione herbicides is owing to a mutation in the objective enzyme, making it lesser susceptible to blockage by these herbicides. The results of enzyme deterrence investigates propose some different modified figures of acetyl CoA carboxylase correlated with various measures of resistance to distinct acetyl CoA carboxylase inhibitors. In contrast, a second biotype was very resistant to sethoxydim (R/S I50 ratio of 420), but had only a low level of resistance to other AOPP and CHD herbicides [57]. A similar pattern was observed in a *Setaria faberi* biotype from Iowa and in a sethoxydimresistant corn line selected in tissue culture [58, 57]. A third pattern of resistance, conferring high-level resistance to fluazifop and lower levels of resistance to other AOPP and CHDs, has been found in a biotype of *Eleusine indica* from Malaysia [59], a *Lolium rigidum* biotype from Australia [60]. In a fourth category, some biotypes are resistant to AOPP herbicides but not to CHDs. These include *L. rigidum* biotype a VLR69 from Australia [61], a *Lolium multiyorum* biotype from Oregon, the USA [62], and *Avena fatua* biotype UM33 from Manitoba, Canada [63]. Similar groupings of resistant biotypes have been proposed in Ref. [64] according to entire plant cross-resistance templates to aryloxyphenoxy propanoate and cyclohexanedione herbicides in *Avena fatua* biotypes from Canada. Because of the two different acetyl CoA carboxylase genes in the weed grasses, this plant family encodes both cytosolic and plastidic figures of the acetyl CoA carboxylase. The target form of acetyl CoA carboxylase for aryloxyphenoxy propanoate and cyclohexanedione herbicides is the plastidic form, and in fact, this form of acetyl CoA carboxylase is modified in resistant weed biotypes [65]. Generally, the different patterns of resistance may be endowed by separate mutations in the gene for

of ACCase [54, 55].

106 Herbicide Resistance in Weeds and Crops

and Cys-2088-Arg [48].

Acetolactate synthase (ALS) is the first enzyme in the biosynthetic for the branched-chain amino acids, such as valine, leucine, and isoleucine. A large number of herbicides, for example, sulfonylurea (SU), imidazolinone (IMI), triazolopyrimidine, pyrimidinyl-thiobenzoates, and sulfonyl-aminocarbonyl-triazolinone effect on acetohydroxyacid synthase (AHAS) catalyzes the formation of both aceto-hydroxybutyrate and acetolactate [68]. The vast AHAS-inhibiting herbicide resistance literature has been thoroughly reviewed [69, 70], so here, we are focusing on last expansions. It was rapidly established that AHAS herbicide-resistant plants could have a mutant, resistant AHAS enzyme [71, 58], and reports of resistant AHAS in many weeds followed. At Pro-197, 11 amino acid substitutions can endow AHAS herbicide resistance [51]. Although faster herbicide detoxification is a mechanism in some biotypes, in most cases, resistance to ALS and AHAS herbicides is endowed by target-site mutations [11, 72]. Target-sitebased ALS resistance is due to point mutations that occur within discrete conserved domains of the ALS gene [11]. Most resistance mutations occur at the Pro-197 position, including one based on a double mutation [32]. Pro-197 mutations confer a high level of resistance to sulfonylurea herbicides, but low or no cross-resistance to imidazolinone herbicides. The Trp591 to Leu mutation confers high levels of resistance to all ALS inhibitors, whereas the Ser670 to Asp and Ala122 to Thr mutations confer a high level of resistance to imidazolinones but little change in sensitivity to sulfonylurea and triazolopyrimidine herbicides [73, 74].

As with triazine resistance, double mutations have been identified that confer higher levels of resistance to ALS inhibitors [75, 76]. Imidazolinone-resistant corn and wheat lines were selected *in vitro* in cell cultures or following seed mutagenesis resistant to various classes of ALS inhibitor [77, 66]. The development of selective uses for these herbicides may result in added selection pressure for resistant weeds, emphasizing the need for careful herbicide management to maintain the long-term usefulness of these herbicides [78, 15].

#### *3.1.6. Resistance to PSII-inhibiting herbicides*

Triazine and phenylurea herbicides do so by binding to the plastoquinone (PQ)-binding site on the D1 protein in the PS II reaction center of the photosynthetic electron transport chain. The D1 protein is coded by the *psb*A gene. PS II herbicide has two major consequences: (a) a shortage of reduced NADP`, which is required for CO2 fixation; and (b) the formation of free radicals which cause photooxidation of important several molecules such as chlorophylls and unsaturated lipids in the chloroplast. Triazine (simazine) resistance in weeds (*Senecio vulgaris*) was first identified in the late 1960s [24, 79, 80]. Since then, resistance to triazine herbicides has been reported in several weed species that many of them have developed in corn monocultures in the North America and Europe [81, 82]. Most s-triazine resistant biotypes show a high level of cross-resistance to other s-triazine herbicides, a lower level of resistance to as-triazinones, but no cross-resistance to phenylurea herbicides [83]. In almost all cases, a Ser264 to Gly mutation in the D1 protein is responsible for conferring resistance in weed biotypes [79]. QB may yet availability this site and transmits electrons to the cytochrome b6/f complex from the PS II reaction center, while the herbicide is absent. Ser264 to Gly mutation has no impact on the affinity of substituted urea herbicides and other PS II electron transport inhibitors, although it decreases the binding affinity of s-triazine and as-triazine herbicides to the D1 protein [39]. Biotypes containing this mutation exhibit a resistance factor of 1000 at the binding site on the D1 protein and 100 at the whole plant level [25, 84]. A resistant biotype of *Portulaca oleracea* has a high level of resistance to atrazine and to linuron, which through a Ser264 to Thr mutation which is the first reportage about D1 Ser264 to Thr mutation in higher plants selected under field conditions. Formerly, in tobacco and potato, this mutation had only been elected through tissue culture [85–87]. Both the Ser264 to Gly and Ser264 to Thr mutations reduce the efficiency of photosynthetic electron transport in the absence of herbicide [88, 89]. Resistance mutations can occur at positions other than Ser264, and mutations at Ser264 do not necessarily confer herbicide resistance. Molecular analysis has revealed that mutations at or close to positions Ser264, Phe265, Phe255, and His215 can affect the binding of PQ or herbicides and play an important part in the development of resistance [79, 11]. These results indicate that a mutation at Ser264 does not necessarily lead to resistance. Several mutations at positions other than Ser264 have been identified that confer resistance to triazine herbicides. Recently, a Val219 to Ile mutation has been identified in *Poa annua* populations resistant to metribuzin and diuron [90]. Val219 to Ile and Ala251 to Val or Thr mutations, without a change at Ser264, were suggested to be responsible for triazine resistance in various cell culture lines of *Chenopodium rubrum* [91]. In Ref. [92], Trebst has discussed amino acid changes between positions 211 and 275, including Phe211 to Ser, Gly256 to Asp, and Leu275 to Phe that confer herbicide resistance in various organisms. Some researchers reported a Ser268 to Pro mutation in soybean cell culture that confers a high level of resistance to both triazine and phenylurea herbicides [93]. Negative cross-resistance has been reported in some instances in which a triazine-resistant biotype is hypersensitive to phenylureas and other PS II-inhibiting herbicides [25, 94]. A *Chlamydomonas* mutant (Phe255 to Tyr) displayed negative cross-resistance to diuron and atrazine-resistant biotypes of *Amaranthus cruentus*, and *Amaranthus hybridus* showed negative cross-resistance to bentazon and pyridate [92, 95].

#### *3.1.7. Resistance to auxin-type herbicides*

Auxin-type herbicides that mimic the endogenous auxin indole acetic acid (IAA) are among the oldest weed control products in use today. Nevertheless, the molecular binding site has not been recognized and the correct mechanism of action is not excellent realized, despite years of intense study. These compounds can motivate protein biosynthesis, and on the other hand, inhibit cell division and growth at low and higher concentrations, usually in the meristematic regions, respectively. The cell wall plasticity and nucleic acid metabolism primarily affect these compounds. The most broadleaf weeds well control through synthetic auxins [96]. Resistance to these herbicides is uncommon, considering their history of intensive use in cereal cropping systems [97].

#### **3.2. Non-target-site herbicide resistance**

to as-triazinones, but no cross-resistance to phenylurea herbicides [83]. In almost all cases, a Ser264 to Gly mutation in the D1 protein is responsible for conferring resistance in weed biotypes [79]. QB may yet availability this site and transmits electrons to the cytochrome b6/f complex from the PS II reaction center, while the herbicide is absent. Ser264 to Gly mutation has no impact on the affinity of substituted urea herbicides and other PS II electron transport inhibitors, although it decreases the binding affinity of s-triazine and as-triazine herbicides to the D1 protein [39]. Biotypes containing this mutation exhibit a resistance factor of 1000 at the binding site on the D1 protein and 100 at the whole plant level [25, 84]. A resistant biotype of *Portulaca oleracea* has a high level of resistance to atrazine and to linuron, which through a Ser264 to Thr mutation which is the first reportage about D1 Ser264 to Thr mutation in higher plants selected under field conditions. Formerly, in tobacco and potato, this mutation had only been elected through tissue culture [85–87]. Both the Ser264 to Gly and Ser264 to Thr mutations reduce the efficiency of photosynthetic electron transport in the absence of herbicide [88, 89]. Resistance mutations can occur at positions other than Ser264, and mutations at Ser264 do not necessarily confer herbicide resistance. Molecular analysis has revealed that mutations at or close to positions Ser264, Phe265, Phe255, and His215 can affect the binding of PQ or herbicides and play an important part in the development of resistance [79, 11]. These results indicate that a mutation at Ser264 does not necessarily lead to resistance. Several mutations at positions other than Ser264 have been identified that confer resistance to triazine herbicides. Recently, a Val219 to Ile mutation has been identified in *Poa annua* populations resistant to metribuzin and diuron [90]. Val219 to Ile and Ala251 to Val or Thr mutations, without a change at Ser264, were suggested to be responsible for triazine resistance in various cell culture lines of *Chenopodium rubrum* [91]. In Ref. [92], Trebst has discussed amino acid changes between positions 211 and 275, including Phe211 to Ser, Gly256 to Asp, and Leu275 to Phe that confer herbicide resistance in various organisms. Some researchers reported a Ser268 to Pro mutation in soybean cell culture that confers a high level of resistance to both triazine and phenylurea herbicides [93]. Negative cross-resistance has been reported in some instances in which a triazine-resistant biotype is hypersensitive to phenylureas and other PS II-inhibiting herbicides [25, 94]. A *Chlamydomonas* mutant (Phe255 to Tyr) displayed negative cross-resistance to diuron and atrazine-resistant biotypes of *Amaranthus cruentus*, and *Amaranthus hybridus* showed negative cross-resistance to ben-

Auxin-type herbicides that mimic the endogenous auxin indole acetic acid (IAA) are among the oldest weed control products in use today. Nevertheless, the molecular binding site has not been recognized and the correct mechanism of action is not excellent realized, despite years of intense study. These compounds can motivate protein biosynthesis, and on the other hand, inhibit cell division and growth at low and higher concentrations, usually in the meristematic regions, respectively. The cell wall plasticity and nucleic acid metabolism primarily affect these compounds. The most broadleaf weeds well control through synthetic auxins [96]. Resistance to these herbicides is uncommon, considering their history of intensive use in

tazon and pyridate [92, 95].

108 Herbicide Resistance in Weeds and Crops

cereal cropping systems [97].

*3.1.7. Resistance to auxin-type herbicides*

Non-target-site-based resistance (NTSR) can confer unpredictable cross-resistance to herbicides. The non-target-site-based resistance mechanisms can interfere with herbicide penetration, translocation, and accumulation at the target site. NTSR is a part of the plant stress response. As such, NTSR is a dynamic process unrolling over time that involves "protectors" directly interfering with herbicide action, and also regulators controlling "protector" expression. NTSR is thus a quantitative trait. Infiltration of the herbicide into the plant and translocation to its site of action, reposition of the herbicide at its site of action, and binding of the herbicide to its target protein are three stages of herbicide action [8].

#### *3.2.1. Decreased herbicide infiltration and displacement*

Decrease in infiltration of herbicide has been reported in resistant weeds and crops for every main herbicide modes of action, that is, glyphosate [6, 98] acetolactate synthase, and acetyl CoA carboxylase inhibitors [99, 100]. This is owing to variations in the some physical and chemical attributes such as physical and chemical properties of the hull in resistant weeds and crops that bring a decline in the maintenance of the herbicides dilution on the foliage and/or a decrease in the influence of herbicides infiltration via the hull. Decrease in dislocation of herbicides has been investigated by other researchers [10, 51]. This phenomenon initiates some limitation in the move of the herbicide in the weeds or crops and in some cases the herbicide compartmenting. Decreased herbicide infiltration and displacement is a main mechanism of resistance to several herbicides, for example, paraquat and glyphosate. It has been made clear that depend on the weed or crop specie, or on the single weed or crop, nontarget-site herbicide resistance toward paraquat inclusive the limited translocation through xylem, sequestration in the cell wall or in the vacuole and decreased uptake into the leaf cells [51, 101]. Limited translocations through the xylem and/or the phloem and/or quick sequestration to the vacuole are events, which occur through the non-target-site herbicide resistance toward glyphosate [6, 51, 102].

#### *3.2.2. Enhanced herbicide degradation*

Enhanced herbicide degradation is certainly the most studied aspect of NTSR. Herbicide degradation is a multistep process involving the coordinated action of several types of enzyme which have several stages. These stages involved the transformation of molecule of herbicide to some hydrophilic metabolite (stage I), the conjugation of hydrophilic metabolites into a plant acceptor molecule (such as a sugar) (stage II), and the exportation of the metabolite(s) into the vacuole and/or the cell walls after additional conjugation, cleaving, and/or oxidation stages [8, 103, 104].

#### *3.2.3. Conservation versus the parallel recompense of herbicide action*

This type of mechanism has been best studied in the case of *Alopecurus myosuroides* NTSR to ACCase repressors. Acetyl-CoA carboxylase (ACCase) inhibitors—herbicides, by interrupting biosynthesis of fatty acids, bring the extrication of active oxygen species that harm the ingredients of cells. Non-target-site-based resistance is mostly conferred through an increase in the expression of peroxidases that support the cells versus oxidative harm in several resistant plants. Hereon, non-target-site-based resistance is not case to an increase in degradation of herbicide in resistant species than sensitive species [8, 101, 105, 106].
