Repeated origins, gene flow, and allelic interactions of herbicide resistance mutations in a widespread agricultural weed

Causal mutations and their frequency in nature are well-characterized for herbicide resistance. However, we still lack understanding of the extent of parallelism in the mutational origin of target-site resistance (TSR), the role of standing variation and gene flow in the spread of TSR variants, and allelic interactions that mediate their selective advantage. We addressed these questions with genomic data from 18 agricultural populations of Amaranthus tuberculatus, which we show to have undergone a massive expansion over the past century, with a contemporary effective population size estimate of 8x107. We found nine TSR variants, three of which were common--showing extreme parallelism in mutational origin and an important role of gene flow in their geographic spread. The number of repeated origins varied across TSR loci and generally showed stronger signals of selection on de novo mutations, but with considerable evidence for selection on standing variation. Allele ages at TSR loci varied from [~]10-250 years old, greatly pre-dating the advent of herbicides. The evolutionary history of TSR has also been shaped by both intra- and inter-locus allelic interactions. We found evidence of haplotype competition between two TSR mutations, their successes in part modulated by either adaptive introgression of, or epistasis with, genome-wide resistance alleles. Together, this work reveals a remarkable example of spatial parallel evolution--the ability of independent mutations to spread due to selection contingent on not only the time, place, and background on which they arise but the haplotypes they encounter.