Balancing Selection in the Human Genome


Balancing selection maintains advantageous diversity in populations by a variety of mechanisms. As a source for functional polymorphism, it contributes to the genetic and phenotypic diversity of present‐day human populations. Classically, most of our understanding of the influence of balancing selection in humans was based on few well‐known examples, but recent advances at the genome scale (made possible by newly available genomic databases and analytical methods) provide further insights on the influence and targets of balancing selection in humans. Such studies have pointed out the uniqueness of the MHC locus, but suggest that more typical cases of balancing selection exist. Our growing understanding of the targets of balancing selection in humans suggests that although this is not a pervasive force in the human genome, it has played a role in the maintenance of functionally relevant polymorphism in humans.

Key Concepts:

  • Balancing selection maintains genetic and phenotypic diversity in populations.

  • Different mechanisms constitute balancing selection, all of which maintain advantageous polymorphism in populations.

  • Balancing selection is not pervasive in humans, but it has shaped the evolution of critical genes for individual survival.

  • The MHC complex in chromosome 6 shows striking, and unique, genetic signatures of balancing selection.

  • Advantageous diversity for MHC‐dependent antigen presentation has shaped the patterns of diversity of diverse genomic loci.

  • The genetic signatures of balancing selection can be identified both by studying individual genes and by analysing genome‐wide patterns of diversity.

  • Genome‐wide analyses are key to identify previously unknown (and unsuspected) targets of natural selection.

  • Targets of balancing selection remain undiscovered in the human genome.

Keywords: balancing selection; population genomics; evolution; human evolution; genome; overdominance; heterosis; frequency‐dependent selection; diversity; polymorphism

Figure 1.

Expected distribution of allele frequencies (site frequency spectrum, SFS) under (a) neutrality; (b) balancing selection with a frequency equilibrium of 0.5; and (c) balancing selection with a frequency equilibrium of 0.2. The x‐axis represents the number of derived alleles observed in the sample, and the y‐axis the frequency of that allele‐frequency bin in the locus. Note the excess of alleles close to the frequency equilibrium.

Figure 2.

Graphical representation of the haploid coalescent process, with sampled present‐day haplotypes on the bottom and generations growing upwards back in time. Downwards and forward in time, lines connect every haplotype with its offspring. In each generation, every haplotype either does not reproduce (its line goes extinct), it has one offspring (it has one line going downwards) or it has more than one offspring (it has more than one line going downwards). The most recent common ancestor (MRCA) of all individuals in the present‐day sample is shown as the transition between the grey lines (which represents extinct lineages) to solid colour. Neutral mutations, which are depicted as circles, appear randomly at a constant rate. Mutations present in lineages observed in the present‐day sample are SNPs and are depicted as open green circles; those that appeared in extinct lineages are not observed and are depicted as grey circles. Upwards and backwards in time, lines connect every haplotype with its parent haplotype (the haplotype present in its parent). Each pair of present‐day haplotypes finds a common ancestor (they coalesce) at some point in the past, until the MRCA where all present‐day haplotypes first coalesce. (a) Coalescent under neutrality: 21 SNPs and (b) coalescent under balancing selection that maintains two forms (blue and red) that differ in one functional SNP (blue and red circle): 38 SNPs.

Figure 3.

Typical haplotype network of a loci under long‐term balancing selection with a frequency equilibrium of 0.5 and limited recombination between the selected forms. This represents the haplotype network of ERAP2. In this case, haplotype A encodes for a functional form of the protein, whereas haplotype B encodes for a nonfunctional form of ERAP2. Reproduced from Andrés et al. ().



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Further Reading

Bamshad M and Wooding SP (2003) Signatures of natural selection in the human genome. Nature Review. Genetics 4: 99–111.

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How to Cite close
Andrés, Aida M(Mar 2011) Balancing Selection in the Human Genome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0022863]