Mismatch between lab-generated and field-evolved resistance to transgenic Bt crops in<i>Helicoverpa zea</i>

Transgenic crops producing crystalline (Cry) proteins from the bacterium <i>Bacillus thuringiensis</i> (Bt) have been used extensively to control some major crop pests. However, many populations of the noctuid moth <i>Helicoverpa zea</i>, one of the most important crop pests in the United States, have evolved practical resistance to several Cry proteins including Cry1Ac. Although mutations in single genes that confer resistance to Cry proteins have been identified in lab-selected and gene-edited strains of <i>H. zea</i> and other lepidopteran pests, the genetic basis of field-evolved resistance to Cry proteins in <i>H. zea</i> has remained elusive. We used a genomic approach to analyze the genetic basis of field-evolved resistance to Cry1Ac in 937 <i>H. zea</i> derived from 17 sites in seven states of the southern United States. We found evidence for extensive gene flow among all populations studied. Field-evolved resistance was not associated with mutations in 20 single candidate genes previously implicated in resistance or susceptibility to Cry proteins in <i>H. zea</i> or other lepidopterans. Instead, resistance in field samples was associated with increased copy number of a cluster of nine trypsin genes. However, trypsin gene amplification occurred in a susceptible sample and not in all resistant samples, implying that this amplification does not always confer resistance and mutations in other genes also contribute to field-evolved resistance to Cry1Ac in <i>H. zea</i>. The mismatch between lab-generated and field-evolved resistance in <i>H. zea</i> is unlike other cases of Bt resistance and reflects challenges for managing this pest.