<p style="text-align: justify;">AP602CL (Clearfield&trade;) spring wheat was not subject to regulation in any jurisdiction except Canada since the development of this herbicide-tolerant line did not employ recombinant DNA technologies. In Canada, regulatory approval is required for use in human food and livestock feed, and for environmental release.</p>

<p style="text-align: justify;">Commercial wheat is comprised mainly of two species: common, or bread wheat (<i>T. aestivum </i>L.) and durum wheat (<i>T. durum</i> Desf.). Bread wheat is classified into several types, based on vernalisation requirement (winter and spring types) and kernel hardness. The hard types of bread wheat are high in protein, especially gliadins and glutenins. The high levels of these protein fractions in the flour impart elasticity to bread dough and allow it to expand during leavening and baking. Soft wheats are low in protein, and have low levels of gliadin and glutenin; these qualities are desirable in products such as cakes and pastries, and in unleavened breads. Durum wheat produces very hard, almost vitreous kernels due to its high protein content. This wheat is milled into semolina for the production of pasta and couscous.</p>

<p style="text-align: justify;">Harvested wheat consists of a naked kernel, unlike other cereals such as rice, barley or oats that retain their hull (<i>i.e.</i>, the palea and lemma). The wheat kernel is loosely enclosed within the palea and lemma of each spikelet; these are eliminated as chaff during threshing. The wheat kernel is milled into white flour by removing the bran, aleurone layers and the germ prior to grinding; whole-wheat flour retains these fractions. By-products of wheat milling include: bran, germ, shorts and middlings. Some of these by-products are used as human food (<i>i.e.</i>, bran, germ), and others, as livestock feed. Grain that does not meet the grade for food use can be used as animal feed, mainly for poultry and swine, but also for cattle. Wheat can also be fed as forage, either as pasture prior to stem elongation, or as ensilage. Wheat is also used in the brewing and distilling industries.</p>

<p style="text-align: justify;">Weeds are a major production problem in wheat cultivation. Weeds compete for light, water and nutrients, and can also cause lodging and problems with harvesting. The seeds of several weed species are almost impossible to clean out of harvested wheat (<i>e.g.</i>, <i>Avena fatua</i> L. wild oats), causing loss of quality and downgrading of the crop. Weeds can be managed using a combination of cultural practices (<i>e.g.</i>, seed bed preparation, use of clean [certified] seed, narrow row spacing, fertilizer banding), integrated weed management (<i>e.g.</i>, weed scouting, economic thresholds) and the use of herbicides. Depending on the weed species present, herbicides can be applied before the crop emerges (<i>e.g.</i>, amitrole, glyphosate, trifluralin), or after (<i>e.g.</i>, 2-4D, bromoxynil, dicamba, fenoxaprop-p-ethyl, MCPA, metsulfuron methyl). The build-up of weed populations can be stemmed by applying herbicides on summer-fallowed fields, and by practicing crop rotation, which allows the use of different herbicides. Rotating among herbicide groups also prevents the development of herbicide-resistant biotypes.</p>

<p style="text-align: justify;">AP602CL (Clearfield&trade;) spring wheat was developed to allow the use of imazamox, an imidazolinone herbicide, as a weed control option in spring wheat production. The mode of action of imazamox consists of inhibiting the activity of acetohydroxyacid synthase (AHAS), an enzyme in plants active in glycolysis and in the biosynthesis of the branched-chain amino acids isoleucine, leucine and valine. The result of the inhibition of AHAS activity is a decrease in protein synthesis, and in an accumulation of toxic levels of alpha-ketoglutarate, all of which cause the eventual death of the plant. While unmodified wheat is not tolerant to imazamox, the line AP602CL has been modified to survive an otherwise lethal application of this herbicide. AP602CL was developed using chemically induced seed mutagenesis and whole plant selection procedures. The herbicide tolerance is due to a mutation in the AHAS gene, which codes for an alteration in the binding site for imazamox in the AHAS enzyme.</p>

<p style="text-align: justify;">Depending on the species, plants contain single or multiple copies of the AHAS genes. The genome of <i>T. aestivum</i> is believed to contain an AHAS multigene family.</p>

<p style="text-align: justify;">Modifications of AHAS genes in various plant species can result in herbicide tolerant phenotypes and typically consist of one amino acid substitution, sufficient to alter the binding site for imidazolinones such that the herbicide no longer inhibits the AHAS enzyme. Several modified AHAS plants have been isolated.</p>

<p style="text-align: justify;">AP602CL was selected from a population of <i>T. aestivum </i> derived by chemical-induced mutagenesis of seed of the wheat variety Gunner. One mutant, tolerant to imidazoline was selected and designated AP602CL. Tolerance to imadazoline was demonstrated by comparison of the activity of the AHAS enzyme extracted from AP602CL to that of wild type plants.</p>

<p style="text-align: justify;">The novel tolerance to imadazoline is under control of the native AHAS promoter and is believed to be constitutively expressed. Sequence information for the modified AHAS gene in AP602CL was submitted.</p>

<p style="text-align: justify;">The levels of valine, leucine and isoleucine produced in wheat are regulated by feedback inhibition of AHAS. Modified AHAS shows similar feedback inhibition to that of unmodified AHAS. AHAS is not known to be an allergen and modified AHAS also does not exhibit characteristics associated with allergens. The protein components of AHAS are not altered in comparison with unmodified Gunner wheat.</p>
