Balancing Selection in the Human Genome

Abstract

Abstract 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.