70
D. Enard
Alleles under balancing selection are alleles where heterozygous individuals
have a greater selective advantage than homozygous individuals (heterozygote
advantage) or where the selective advantage of either heterozygous individuals
carrying the allele on one chromosome or homozygous individuals carrying the
allele on both chromosomes depends on the frequency of the allele (frequencydependent selection). In both cases of heterozygote advantage and frequencydependent selection, the effect of selection is to maintain the frequency of the
selected alleles at intermediate frequencies, for a number of generations greater than
expected under genetic drift alone.
Alleles under purifying selection, also known as negative selection, are alleles
with deleterious consequences for their carriers. Deleterious alleles reduce the
reproductive success of individuals. By reducing reproductive success, deleterious
alleles are removed from populations because individuals carrying them reproduce
less than individuals free of such alleles. Strongly deleterious alleles are eliminated
from populations rapidly enough that they never make it to appreciable frequencies.
Weakly deleterious alleles can initially reach appreciable frequencies due to genetic
drift and sometimes, in small populations, can become fixed by drift in spite of
selection (Ohta and Gillespie 1996).
For further discussion of the mathematical details of the basics of natural selection, we recommend that readers consult several excellent textbooks on population
genetics (Hartl and Clark 2007; Hamilton 2009; Charlesworth and Charlesworth
2010).
4.1.2 The Effect of Selection on Linked Neutral Sites
Natural selection affects not only the frequency of the selected variants themselves
but also the linked neutral genetic variation. Neutral variants, as opposed to selected
ones, have no effect on an individual’s reproductive success. In the absence of
selection, their evolution is driven by random genetic drift, where the frequency of
a variant fluctuates over generations as a result of the random sampling of gametes
at each generation. The probability that a new neutral mutation becomes fixed is
only one over twice the effective population size. In other words, the vast majority
of neutral variants never reach fixation. The crucial difference between neutral and
selected variants is that when selection is strong enough, it can change the frequency
of linked neutral variants much faster than genetic drift alone. Only those neutral
variants that are genetically linked to one or several selected variants also experience
faster changes in their frequencies. In the case of positive directional selection,
neutral variants are said to hitchhike with the selected variants. It is therefore
possible to localize and/or quantify natural selection in a genome by detecting the
effect of selected variants on linked neutral variation. Regions of the genome where
the frequency of neutral variants has changed the most are also the ones that are
more likely to be influenced by linkage to sites affected by natural selection.
There are three forms of natural selection that influence patterns of linked neutral
diversity. The first is positive directional selection and results in a phenomenon
D. Enard
Alleles under balancing selection are alleles where heterozygous individuals
have a greater selective advantage than homozygous individuals (heterozygote
advantage) or where the selective advantage of either heterozygous individuals
carrying the allele on one chromosome or homozygous individuals carrying the
allele on both chromosomes depends on the frequency of the allele (frequencydependent selection). In both cases of heterozygote advantage and frequencydependent selection, the effect of selection is to maintain the frequency of the
selected alleles at intermediate frequencies, for a number of generations greater than
expected under genetic drift alone.
Alleles under purifying selection, also known as negative selection, are alleles
with deleterious consequences for their carriers. Deleterious alleles reduce the
reproductive success of individuals. By reducing reproductive success, deleterious
alleles are removed from populations because individuals carrying them reproduce
less than individuals free of such alleles. Strongly deleterious alleles are eliminated
from populations rapidly enough that they never make it to appreciable frequencies.
Weakly deleterious alleles can initially reach appreciable frequencies due to genetic
drift and sometimes, in small populations, can become fixed by drift in spite of
selection (Ohta and Gillespie 1996).
For further discussion of the mathematical details of the basics of natural selection, we recommend that readers consult several excellent textbooks on population
genetics (Hartl and Clark 2007; Hamilton 2009; Charlesworth and Charlesworth
2010).
4.1.2 The Effect of Selection on Linked Neutral Sites
Natural selection affects not only the frequency of the selected variants themselves
but also the linked neutral genetic variation. Neutral variants, as opposed to selected
ones, have no effect on an individual’s reproductive success. In the absence of
selection, their evolution is driven by random genetic drift, where the frequency of
a variant fluctuates over generations as a result of the random sampling of gametes
at each generation. The probability that a new neutral mutation becomes fixed is
only one over twice the effective population size. In other words, the vast majority
of neutral variants never reach fixation. The crucial difference between neutral and
selected variants is that when selection is strong enough, it can change the frequency
of linked neutral variants much faster than genetic drift alone. Only those neutral
variants that are genetically linked to one or several selected variants also experience
faster changes in their frequencies. In the case of positive directional selection,
neutral variants are said to hitchhike with the selected variants. It is therefore
possible to localize and/or quantify natural selection in a genome by detecting the
effect of selected variants on linked neutral variation. Regions of the genome where
the frequency of neutral variants has changed the most are also the ones that are
more likely to be influenced by linkage to sites affected by natural selection.
There are three forms of natural selection that influence patterns of linked neutral
diversity. The first is positive directional selection and results in a phenomenon