The standing pool of genomic structural variation in a natural population of Mimulus guttatus

TL;DR

This study systematically characterizes structural variants, especially indels, in a natural Mimulus guttatus population, revealing their frequency, gene impact, and evidence of selection, thus advancing understanding of genetic variation and evolution.

Contribution

It provides a comprehensive analysis of indel variation in a natural population, highlighting their frequency, gene interactions, and signatures of selection, which was previously underexplored.

Findings

Most indels are rare and under purifying selection.

Nearly 600 genes are affected by indels, especially defense genes.

Some high-frequency indels show signs of recent positive selection.

Abstract

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.