Characterizing the detectable and invisible fractions of genomic loci under balancing selection

Abstract Balancing selection refers to scenarios where selection maintains genetic polymorphisms affecting fitness and its components. Empirical studies have documented specific cases of balancing selection, yet the general prevalence of balanced polymorphisms within genomes remains a topic of longstanding debate. Although genome-wide scans for signals of balancing selection suggest that it is rare, current methods are notoriously conservative and may identify only a small and unrepresentative fraction of loci evolving under balancing selection. What, then, are the proportions of loci under balancing selection that are detectable versus invisible to genome scans? Here, we address this question using a combination of analytical modeling and population genetic simulations. Our results provide quantitative support for the intuition that a large fraction of loci under balancing selection will be invisible to standard tests for balancing selection, with the detectable loci representing a biased subset with large and symmetrical fitness effects on different fitness components. Quantifying power across parameters that vary between species also shows that the detectable and invisible fractions of genomic loci under balancing selection are likely to differ substantially between organisms. For example, a Drosophila melanogaster-like ratio of mutation to recombination rates (∼0.1) reduces detection power by roughly a quarter of the power expected with a human-like ratio (∼1). This, combined with other evidence suggesting that balancing selection could be common in D. melanogaster, showcases how our appreciation of the prevalence of balancing selection is limited by our ability to detect its genomic signals, especially in those species where it might be common.