Natural selection drives genome-wide evolution via chance genetic associations

Understanding selection's impact on the genome is a major theme in biology. Functionally neutral genetic regions can be affected indirectly by natural selection, via their statistical association with genes under direct selection. The genomic extent of such indirect selection, particularly across loci not physically linked to those under direct selection, remains poorly understood, as does the time scale at which indirect selection occurs. Here, we use field experiments and genomic data in stick insects, deer mice and stickleback fish to show that widespread statistical associations with genes known to affect fitness cause many genetic loci across the genome to be impacted indirectly by selection. This includes regions physically distant from those directly under selection. Then, focusing on the stick insect system, we show that statistical associations between SNPs and other unknown, causal variants result in additional indirect selection in general and specifically within genomic regions of physically linked loci. This widespread indirect selection necessarily makes aspects of evolution more predictable. Thus, natural selection combines with chance genetic associations to affect genome-wide evolution across linked and unlinked loci and even in modest-sized populations. This process has implications for the application of evolutionary principles in basic and applied science.