Testing for Adaptive Evolution:
1. Ka/Ks >1
2. Ka/Ks > Pa/Ps
3. Neutral Polymorphism: does not require recurrent adaptive evolution, for unique (a single)
and recent events of adaptive evolution. Not on direct targets.
Effect of Positive Selection on Neutral Polymorphism
1. Reduction in Neutral Variation: Selective Sweep where positive mutation spreads, and
genetic hitchhiking and thus reduce in neutral variations
2. Increase in linkage disequilibrium: strong haplotype set of SNPs on a single chromosome of a
chromosome pair that is statistically associated.
3. Shift in SNP frequencies: excess of rare neutral polymorphisms, reduction in diversity due to
elimination of common neutral variations.
4. Increased differentiation among populations: higher Fst, fraction of variation between
populations. Even if the 2 populations are both experiencing positive selection , there might
also be an increase in differentiation if the advantageous mutations are happening
Distinguishing Natural Selection vs. Demographic history: Genome-wide patterns of diversity
Demographic effects should act genome-wide in a consistent manner
Natural selection causes inconsistencies among genes in their patterns of diversity
How do we apply it? Characterize genomic distribution of patterns of genetic diversity. Are
there inconsistencies across genes in their history or a historical model?
Sharp drop in level in diversity and excess of rare variants (reduced variability) and big
increase in LD.
Signal of Positive Selection: Example of FOXP2
Mutations in gene within humans known to confer specific effects on language
First gene possibly implicated in development of human language ability Two AA differences from chimpanzees, one possibly functional
Human Lineage: 2/0 where the left (2) is the NS changes and the right (0) is the S changes.
The other primates have no AA changes relative to humans. We are experiencing more NS
changes after we diverged from chimpanzees
Unusual excess of low-frequency polymorphisms (rare variants): only 1 in 315 reference
genes showed an extreme excess as the FOXP2 gene
That particular gene underwent selective sweep consistent with selection happening in the
last 200,000 years, just like the FOXP2 gene
Evolution of Skin Pigmentation:
Local Adaptation Associated with UV radiation
Tradeoffs associated with light and dark pigmentation:
Less UV =reduces vitamin D synthesis. Lighter, as needing to get enough vitamin D
Higher UV: interferes with folate. Darker, prevent breaking down of folate
Positive Selection on Skin Pigmentation
SLC24A5 implicated in pigmentation
Reduction in polymorphism in European populations
Includes 1 out of 2 fixed differences between European and East Asian samples (no high
levels of differentiation between human populations)
Nielsen: scanning the genome for positive selection. CLR statistic to compare probability that
a region has its own SNP frequency distribution relative with the probability that its part of
the genome-wide distribution. Measure of unusualness. Own allele-frequency spectrum
compared to on that can fit into the gene-wide spectrum
SLC is highly differentiated and most unusual: population specific positive selection
Williamson et al: 101 regions under positive selection, as much as 10% of genome linked to
regions subject to selective sweeps due to LD and positive selection.
M-K found very little evidence of positive selection. However single selection events tests
have found a good amount of strong positive selection: pigmentation, immunity and olfactory
Very recent positive selection and local adaptation may often NOT show fixation events
Scans for alleles at high frequency with low diversity: SNP at high frequency, chances are