Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion

We use population genetics theory and computer simulations to demonstrate that population bottlenecks cause a characteristic mode-shift distortion in the distribution of allele frequencies at selectively neutral loci. Bottlenecks cause alleles at low frequency (< 0.1) to become less abundant than alleles in one or more intermediate allele frequency class (e.g., 0.1-0.2). This distortion is transient and likely to be detectable for only a few dozen generations. Consequently only recent bottlenecks are likely to be detected by tests for distortions in distributions of allele frequencies. We illustrate and evaluate a qualitative graphical method for detecting a bottleneck-induced distortion of allele frequency distributions. The simple novel method requires no information on historical population sizes or levels of genetic variation; it requires only samples of 5 to 20 polymorphic loci and approximately 30 individuals. The graphical method often differentiates between empirical datasets from bottlenecked and nonbottlenecked natural populations. Computer simulations show that the graphical method is likely (P > .80) to detect an allele frequency distortion after a bottleneck of < or = 20 breeding individuals when 8 to 10 polymorphic microsatellite loci are analyzed.