GENE30001 Lecture Notes - Lecture 6: Mutation Rate, Genetic Drift, Gametogenesis
14 Jun 2018
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MK - McDonald Kreitman Test: As mentioned in
the blurb, under a neutral model: the patterns of
nucleotide variation w/i species = patterns of
nucleotide variation b/w species (Dn/Ds=Pn/Ps)
It's simple and robust w/o assumptions
Input: seq w/i & b/w species
Output: reject neutral model/assumptions
The MK test is a test of the neutral model of DNA sequence divergence between two species (McDonald
& Kreitman 1991). Like the HKA test it is named for it authors, McDonald and Kreitman. The MK test is
also conceptually similar to the HKA test because it too establishes expected ratios of two classes of DNA
changes at a single locus under neutrality. The MK test requires DNA sequence data from a single coding
gene. The sample of DNA sequences is taken from multiple individuals of a focal species to estimate
polymorphism. The test also requires a DNA sequence at the same locus from another species to
estimate divergence.
The neutral expectations for the MK test are given in Table 8.6. The two classes of DNA change used in
the MK test are synonymous and nonsynonymous (or replacement) changes. Nonsynonymous mutations
within coding regions may alter the amino acid specified by a codon. Due to the redundancy of the
genetic code, some mutations within coding regions will not change the amino acid specified by the
codon and are therefore synonymous changes.
If genetic drift is the only process influencing the fate of a new mutation, levels of polymorphism and
divergence within each category of DNA change should be correlated because they are both determined
in part by the mutation rate. Fixed differences between species are caused by mutations that have gone
to fixation, with expected divergence under neutral theory of 2Tμ. Nucleotide sites that have two or
more nucleotides within the focal species exhibit polymorphism, with an expected level of 4Neμ under
neutral theory. Since synonymous and nonsynonymous mutations may occur at different rates, we can
assign each category of DNA change a different rate (μN and μS). Both the ratio of nonsynonymous and
synonymous fixed differences and the ratio of nonsynonymous and synonymous polymorphic sites are
expected to be equal to μN/μS under neutral theory. The MK test therefore compares these
two ratios for equality as a test of neutral theory. The neutral case illustration in Table 8.6b gives an
example where μN < μS and where there is a higher level of polymorphism than divergence.
Nonetheless, the ratios of the number of nonsynonymous over synonymous changes are constant for
fixed differences and polymorphic sites as expected if both classes of mutations are neutral.
Examples of Bio processes affected by
positive selection
Immunity and defence
-
T-cell mediated
-
Gametogenesis
-
Antibody mediated immunity
-
Inhibition of apoptosis
-
dN/dS screens only pick up selection that
favours lots of a.a change relative to silent
site change
44
24
68
9
59
Non-syn
Syn
Polymorphism
44*9/68=
5.8235
44*59/68=
38.1765
Divergence
24*9/68=
3.1765
24*59/68=
20.8235
=> The neutral model isn't holding.
Lecture 6: dN/dS continued and McDonald Kreitman Test
Wednesday, 22 June 2016
3:57 PM
Lecture Notes 1- 12 Molecular Evolution and Population Genetics Page 1
Document Summary
Lecture 6: dn/ds continued and mcdonald kreitman test. Mk - mcdonald kreitman test: as mentioned in the blurb, under a neutral model: the patterns of nucleotide variation w/i species = patterns of nucleotide variation b/w species (dn/ds=pn/ps) Examples of bio processes affected by positive selection. Inhibition of apoptosis dn/ds screens only pick up selection that favours lots of a. a change relative to silent site change. The mk test is a test of the neutral model of dna sequence divergence between two species (mcdonald. Like the hka test it is named for it authors, mcdonald and kreitman. The mk test is also conceptually similar to the hka test because it too establishes expected ratios of two classes of dna changes at a single locus under neutrality. The mk test requires dna sequence data from a single coding gene. The sample of dna sequences is taken from multiple individuals of a focal species to estimate polymorphism.
