  Major unresolved questions in evolutionary genetics include determining the
contributions of different mutational sources to the total pool of genetic
variation in a species, and understanding how these different forms of genetic
variation interact with natural selection. Recent work has shown that
structural variants (insertions, deletions, inversions and transpositions) are
a major source of genetic variation, often out-numbering single nucleotide
variants in terms of total bases affected. Despite the near ubiquity of
structural variants, major questions about their interaction with natural
selection remain. For example, how does the allele frequency spectrum of
structural variants differ when compared to single nucleotide variants? How
often do structural variants affect genes, and what are the consequences? To
begin to address these questions, we have systematically identified and
characterized a large set submicroscopic insertion and deletion (indel)
variants (between 1 kb to 200 kb in length) among ten individuals from a single
natural population of the plant species Mimulus guttatus. After extensive
computational filtering, we focused on a set of 4,142 high-confidence indels
that showed an experimental validation rate of 73%. All but one of these indels
were < 200 kb. While the largest were generally at lower frequencies in the
population, a surprising number of large indels are at intermediate
frequencies. While indels overlapping with genes were much rarer than expected
by chance, nearly 600 genes were affected by an indel. NBS-LRR defense response
genes were the most enriched among the gene families affected. Most indels
associated with genes were rare and appeared to be under purifying selection,
though we do find four high-frequency derived insertion alleles that show
signatures of recent positive selection.
