Population genetic studies display an astonishing degree of genetic diversity, making understanding the generation and maintenance of genetic diversity a major focus of evolutionary biology. Mutation generates variation, but directional selection will remove variation, leaving the neutral process of genetic drift as a likely cause. Another possible mechanism is frequency-dependent selection, that is, differential survival and reproduction based on allele or genotype frequencies of other individuals in the same population. Negative frequency-dependent selection favours rare genotypes and promotes genetic variation in populations. Positive frequency-dependent selection favours common alleles, accelerates the loss of rare alleles and decreases genetic variation. Pathogen–host coevolution, sex ratio, self-sterility alleles and mimicry may often result from frequency-dependent selection. For example, the African sleeping sickness parasite Trypanosoma brucei sequentially changes surface antigens as hosts develop antibodies. Host antibodies target the most common antigens, and frequency-dependent selection preserves genetic diversity of antigens of parasites and antibodies of their hosts.

Key Concepts:

• Frequency-dependent selection occurs when the fitness of a genotype depends on whether it is rare or common, that is, an individual's fitness is affected by allele or genotype frequencies of other individuals in the same population.
  
• Pathogen–host coevolution, sex ratio, self-sterility alleles and mimicry are situations where frequency-dependent selection is often hypothesised to be important in maintaining genetic variation.
  
• A central focus of evolutionary biology is understanding roles of neutral processes (e.g. genetic drift) versus selection (e.g. frequency dependence, spatial or temporal environmental variation and heterozygote advantage) in maintaining the surprisingly large amount of genetic variation.
  
• Frequency-dependent selection is an intuitively appealing mechanism for maintaining genetic variation: when a genotype becomes common, its fitness declines and different, rare genotypes are favoured.
  
• Population genetic models show that negative frequency dependence (higher fitness of rare alleles) promotes genetic variation; and positive frequency dependence (selection favours common alleles) accelerates the loss of rare alleles, decreasing genetic variation.
  
• Balanced polymorphism from heterozygote advantage, spatial/temporal variation in fitness and disruptive selection are alternate mechanisms for maintaining genetic polymorphisms.
  
• Documentation of frequency-dependent selection requires demonstrating an observed polymorphism is in fact genetic, followed by testing for frequency dependence rather than balanced polymorphism or fluctuating selection. There are several excellent examples of documenting frequency-dependent selection in nature.
  
• Reviews suggest about 30% of cases of alternative reproductive phenotypes and resource polymorphisms might be frequency-dependent selection.
  
• Future studies to understand the role of frequency-dependent selection in helping parasites avoid host immune responses may be key to human efforts to develop vaccines.