RT Journal Article SR Electronic T1 High genetic diversity can contribute to extinction in small populations JF bioRxiv FD Cold Spring Harbor Laboratory SP 678524 DO 10.1101/678524 A1 Kyriazis, Christopher C. A1 Wayne, Robert K. A1 Lohmueller, Kirk E. YR 2019 UL http://biorxiv.org/content/early/2019/06/21/678524.abstract AB Human-driven habitat fragmentation and loss has led to a proliferation of small and isolated plant and animal populations that may be threatened with extinction by genetic factors. The prevailing approach for managing these populations is to maintain high genetic diversity, which is often equated with fitness. Increasingly, this is being done using genetic rescue, where individuals from populations with high genetic diversity are translocated to small populations with high levels of inbreeding. However, the potentially negative consequences of this approach have recently been highlighted by the demise of the gray wolf population on Isle Royale, which only briefly recovered after genetic rescue by a migrant from the large mainland wolf population and then declined to the brink of extinction. Here, we use ecologically-motivated population genetic simulations to show that extinction risk in small populations is often increased by maximizing genetic diversity but is consistently decreased by minimizing deleterious variation. Surprisingly, we find that small populations that are founded or rescued by individuals from large populations with high genetic diversity have an elevated risk of extinction due to the high levels of recessive deleterious variation harbored by large populations. By contrast, we show that genetic rescue or founding from small or moderate-sized populations leads to decreased extinction risk due to greater purging of strongly deleterious variants. Our findings challenge the traditional conservation paradigm that focuses on genetic diversity in assessing extinction risk in favor of a new view that emphasizes minimizing deleterious variation. These insights have immediate implications for managing small and isolated populations in the increasingly fragmented landscape of the Anthropocene.