Theory suggests that the risk of extinction by mutation accumulation can be comparable to that by environmental stochasticity for an isolated population smaller than a few thousand individuals. Here we show that metapopulation structure, habitat loss or fragmentation, and environmental stochasticity can be expected to greatly accelerate the accumulation of mildly deleterious mutations, lowering the genetic effective size to such a degree that even large metapopulations may be at risk of extinction. Because of mutation accumulation, viable metapopulations may need to be far larger and better connected than would be required under just stochastic demography. K imura, Maruyama, and Crow (1) first noted that mildly deleterious mutations may create a considerably larger mutational load in small populations than more deleterious mutations. Deleterious mutations impose a load on populations through a reduction in the mean survivorship and͞or reproductive rates of individuals (2-5). In very large, effectively infinite populations, an equilibrium mutation load exists that is independent of the mutational effect (2, 3, 5, 6). However, in sufficiently small isolated populations, mildly deleterious mutations may be a potent extinction force, because individually they are nearly invisible to natural selection, although causing an appreciable cumulative reduction in population viability (1,5,(7)(8)(9)(10)(11). Theory suggests that the accumulation of mildly deleterious mutations can be comparable to environmental stochasticity in causing extinction of populations smaller than a few thousand individuals (8,12,13).All previous theoretical work on extinction caused by mutation accumulation has focused on a single panmictic population, but most populations have some degree of subdivision, which may greatly magnify the stochastic development of mutation load (14,15). Moreover, most theoretical work on extinction has focused on only one or two extinction mechanisms at a time, for reasons of mathematical tractability. But demographic (16, 17), environmental (16, 17), and genetic stochasticity (8, 10, 11) operate simultaneously in natural populations, and their synergy may have a strong impact on the probability of extinction (12,13,(18)(19)(20)(21)(22).
Genetic and Demographic ModelWe simulate the dynamics of metapopulation extinction using a biologically realistic model that includes stochastic demographic (17, 23), environmental (17, 23), and genetic (24) mechanisms. Our individual-based model (25) includes population dynamics within each patch, explicit spatial structure, and an explicit representation of each diploid genome (10,11,17,23,24).We parameterize the genetic mechanisms in our model using values from a broad array of empirical studies. Independent data on a diversity of organisms suggest that the genomic deleterious mutation rate, U, is frequently on the order of 0.1 to 1 per individual per generation in multicellular eukaryotes, and that the average homozygous and heterozygous effects of such mutations are typically le...