k-mer-based diversity scales with population size proxies more than nucleotide diversity in a meta-analysis of 98 plant species.

Abstract

A key prediction of neutral theory is that the level of genetic diversity in a population should scale with population size. However, as was noted by Richard Lewontin in 1974 and reaffirmed by later studies, the slope of the population size-diversity relationship in nature is much weaker than expected under neutral theory. We hypothesize that one contributor to this paradox is that current methods relying on single nucleotide polymorphisms (SNPs) called from aligning short reads to a reference genome underestimate levels of genetic diversity in many species. As a first step to testing this idea, we calculated nucleotide diversity ( $\pi$ ) and $k$ -mer-based metrics of genetic diversity across 112 plant species, amounting to over 205 terabases of DNA sequencing data from 27,488 individuals. After excluding 14 species with low coverage or no variant sites called, we compared how different diversity metrics correlated with proxies of population size that account for both range size and population density variation across species. We found that our population size proxies scaled anywhere from about 3 to over 20 times faster with $k$ -mer diversity than nucleotide diversity after adjusting for evolutionary history, mating system, life cycle habit, cultivation status, and invasiveness. The relationship between $k$ -mer diversity and population size proxies also remains significant after correcting for genome size, whereas the analogous relationship for nucleotide diversity does not. These results are consistent with the possibility that variation not captured by common SNP-based analyses explains part of Lewontin's paradox in plants, but larger scale pangenomic studies are needed to definitively address this question.