Genetic variation underpins evolutionary change, but mutation accumulation increases genetic load. Various factors affect the extent of load, such as population size and breeding system, but other important determinants remain unexplored. In particular, whole-genome duplication (WGD)-a pervasive macromutation occurring broadly across Eukaryotes-remains poorly understood in terms of its impact on neutral and selective processes within populations. Using iterative forward simulations and empirical analysis of 632 short- and 16 long-read sequenced individuals of Arabidopsis arenosa (in 23 diploid and 42 natural autotetraploid populations), we measure the effects of WGD on genome-wide diversity and mutation load. Our simulations show how genetic variation gradually rises in autotetraploids due to increased mutational target size. Moreover, mutation load increases due to relaxed purifying selection as ploidies rise, when deleterious mutations are masked by additional chromosome copies. Empirical data confirm these patterns, showing significant increases in nucleotide diversity, ratios of nonsynonymous to synonymous SNPs, and numbers of indels and large structural variants in A. arenosa autotetraploids. However, a rather modest increase in load proxies together with a broad distribution and niche of autotetraploids suggests load accumulation has not yet limited their successful expansion. Overall, we demonstrate a complex interplay between neutral processes and purifying selection in shaping genetic variation following WGD and highlight ploidy as an important determinant of mutation load, genetic diversity, and therefore adaptive potential in natural populations.

Department of Botany Faculty of Science Charles University Prague 12800 Czech Republic

Department of Ecology Environment and Plant Sciences Science for Life Laboratory Stockholm University Stockholm 171 65 Sweden

Institute of Botany Czech Academy of Sciences Průhonice 25243 Czech Republic

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice 37005 Czech Republic

Linnean Centre for Plant Biology Department of Plant Biology Uppsala BioCenter Swedish University of Agricultural Sciences Uppsala 75007 Sweden

Production Systems Natural Resources Institute Finland Jokioinen 31600 Finland

School of Life Sciences University of Nottingham Nottingham NG7 2RD United Kingdom

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Multiple Autopolyploid Arabidopsis lyrata Populations Stabilized by Long-Range Adaptive Introgression Across Eurasia