4 Types of Natural Selection and Tests of Selection
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the advantageous mutation will increase in frequency due to selection in spite of
genetic drift. In a small population, genetic drift is strong, and even mutations
with high selection coefficients can experience many ups and downs in frequency
before reaching fixation. In a large population, genetic drift is weaker, and for the
same selection coefficient, there are systematically more ups than downs on the
road to fixation. In other words, as the intensity of selection increases, the path to
fixation becomes more deterministic and shorter. The faster the fixation, the fewer
recombination events and the larger the region around the selected mutation with
reduced diversity and skewed SFS and haplotype structure. Selective sweeps leave a
larger footprint in regions of the genome with lower recombination. For this reason,
if recombination rates are well known, the size of the genomic region affected by
hitchhiking can be used to estimate the intensity of selection.
(B) Balancing Selection
Balancing selection occurs when selection maintains polymorphism at a specific frequency in the population. Balancing selection happens in three different situations:
in the case of heterozygous advantage, in the case of frequency-dependent selection,
and in the case of fluctuating selection. In heterozygous advantage, heterozygous
individuals have, on average, higher reproductive success than homozygous ones. At
the selected site, allelic variants tend to oscillate around an equilibrium frequency.
In frequency-dependent selection, the selective advantage of an initially uncommon
allele depends on its frequency and results in balancing selection if the equilibrium
is at intermediate frequencies between the different alleles at the selected site. In
the case of fluctuating selection, the direction of selection can fluctuate in time and
space in such a way that advantageous alleles are maintained for extended periods
of time in a population.
For both heterozygote advantage and frequency-dependent selection, the initial
phase is very similar to the case of hitchhiking (Charlesworth 2006). A de novo
mutation spreads quickly to the equilibrium frequency (the equilibrium frequency
for heterozygote advantage). Linked neutral variants or haplotypes are also driven
to intermediate frequencies, much like in the initial phase of a hitchhiking event.
In other words, balancing selection is first characterized by a short phase of
hitchhiking that results in a partial sweep. Such partial sweeps leave an excess
of intermediate allele frequencies in the SFS and also result in larger than usual
intermediate-frequency haplotypes. The second phase of balancing selection is
usually much more extended in time. Once the equilibrium frequency has been
reached, this equilibrium is maintained for a large number of generations. The
stronger the selection, the longer the equilibrium is maintained. The neutral variants
that initially hitchhiked together with the new mutation are also maintained to
the equilibrium frequency as long as they are not dissociated by recombination.
Soon after the establishment of the equilibrium, there is an excess of intermediatefrequency neutral alleles in a large region surrounding the balanced site. With
time, however, recombination breaks down the linkage between the balanced
site and neutral variants, and the region with an excess of intermediate variants
shrinks a bit more every generation. Ultimately, neutral variation is affected by
75
the advantageous mutation will increase in frequency due to selection in spite of
genetic drift. In a small population, genetic drift is strong, and even mutations
with high selection coefficients can experience many ups and downs in frequency
before reaching fixation. In a large population, genetic drift is weaker, and for the
same selection coefficient, there are systematically more ups than downs on the
road to fixation. In other words, as the intensity of selection increases, the path to
fixation becomes more deterministic and shorter. The faster the fixation, the fewer
recombination events and the larger the region around the selected mutation with
reduced diversity and skewed SFS and haplotype structure. Selective sweeps leave a
larger footprint in regions of the genome with lower recombination. For this reason,
if recombination rates are well known, the size of the genomic region affected by
hitchhiking can be used to estimate the intensity of selection.
(B) Balancing Selection
Balancing selection occurs when selection maintains polymorphism at a specific frequency in the population. Balancing selection happens in three different situations:
in the case of heterozygous advantage, in the case of frequency-dependent selection,
and in the case of fluctuating selection. In heterozygous advantage, heterozygous
individuals have, on average, higher reproductive success than homozygous ones. At
the selected site, allelic variants tend to oscillate around an equilibrium frequency.
In frequency-dependent selection, the selective advantage of an initially uncommon
allele depends on its frequency and results in balancing selection if the equilibrium
is at intermediate frequencies between the different alleles at the selected site. In
the case of fluctuating selection, the direction of selection can fluctuate in time and
space in such a way that advantageous alleles are maintained for extended periods
of time in a population.
For both heterozygote advantage and frequency-dependent selection, the initial
phase is very similar to the case of hitchhiking (Charlesworth 2006). A de novo
mutation spreads quickly to the equilibrium frequency (the equilibrium frequency
for heterozygote advantage). Linked neutral variants or haplotypes are also driven
to intermediate frequencies, much like in the initial phase of a hitchhiking event.
In other words, balancing selection is first characterized by a short phase of
hitchhiking that results in a partial sweep. Such partial sweeps leave an excess
of intermediate allele frequencies in the SFS and also result in larger than usual
intermediate-frequency haplotypes. The second phase of balancing selection is
usually much more extended in time. Once the equilibrium frequency has been
reached, this equilibrium is maintained for a large number of generations. The
stronger the selection, the longer the equilibrium is maintained. The neutral variants
that initially hitchhiked together with the new mutation are also maintained to
the equilibrium frequency as long as they are not dissociated by recombination.
Soon after the establishment of the equilibrium, there is an excess of intermediatefrequency neutral alleles in a large region surrounding the balanced site. With
time, however, recombination breaks down the linkage between the balanced
site and neutral variants, and the region with an excess of intermediate variants
shrinks a bit more every generation. Ultimately, neutral variation is affected by