Identification of Genes Subject to Adaptive Evolution (HKA Test):
Different genes are compared to each other, and for different genes is the ratio of divergence
Contrasts the ratio of polymorphism to divergence at silent sites for two or more genes.
Neutral theory: P and D ratio should give an estimate of Ne, the Ne should be the same
under neutral model ratio. Is the Ne the same throughout the genome? Selective sweep will
reduce the Ne and coalesce time
Significant departure from neutral expectation consistent with selection acting at one or
Positive selection: P/D < neutral genes, selective sweep, reduced diversity surrounding the
Balancing selection: P/D > neutral genes, increase diversity surrounding the selected site.
However if it persist for really long time, that means a lot of time for recombination to
happen and that means that any linked neutral sites that are with the functional allele should
eventually recombine with the background, balancing selection is hard to detect. Since time
can break down the hitchhiking effect.
Balancing Selection is really rare
Balancing Selection at the ABO blood group: Look at the functional regions where the AA
polymorphisms are. Human B allele is more similar to gorilla B allele than to the human A
and O allele, elevated diversity where polymorphism is maintained ever since we diverged
from the species. Look at narrow regions.
Role of recombination rate in structuring genetic diversity: Natural selection at linked loci
High recombination: if there is an advantageous mutation, it is going to spread however
there is not much sweep signal. Spread Sweep Recombine
Low recombination: if there is an advantageous mutation, there will be more selective sweep.
Thus if positive selection is happening often enough, there will be a positive correlation
between the rate of recombination and amount of neutral variants. High recombination =
higher diversity, lower recombination = lower diversity
Signal of Genome-Wide Linked Selection: higher recombination will have 1) slight
correlation divergence between species, 2) stronger correlation with diversity and 3) positive
correlation with diversity/divergence
Divergence produce a control to the neutral mutation rate, to make sure that high
recombination are not due to higher mutation rate Signal of Genome-Wide Linked Selection:
If genes are subject to a lot of positive selection, as you get closer to the genes we expect
neutral diversity to drop. Selective sweep for NS AA changes, stronger regions of low
recombination and as it gets closer to genes. Positive selection?
Purifying selection: an alternative to positive selection. If deleterious mutations appearing
every generation, high recombination are eliminating deleterious mutations and that should
have little effect on linked neutral diversity. Low recombination and deleterious mutation that
will eliminate all the linked neutral variation. Purifying selection in low recombination is
reducing the Ne of alleles, and neutral variation and negative selection can lead to this
correlation in diversity also.
Purifying and Positive Selection can both lead to a correlation with Ne and recombination
Recent study examining patterns of diversity in relation to recombination rates suggests that it
can be explained by purifying selection
Testing Genome-Wide Positive Selection: Linking M-K type tests with hitchhiking
M-K: Excess of NS divergence between species
Hitchhiking: signals of low diversity
Sella: Lineage specific changes in one species, the AA fixations that