Transcript Positive Darwinian Selection

… and what about
positive Darwinian selection?
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We have already discussed a test
based on the ratio of fixed to
polymorphic differences
We note that the McDonald-Kreitman test
requires data from many individuals from two
populations or species. Let’s assume we only
have one sequence from each species.
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The KA/KS test requires two
aligned sequences only.
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The assumptions of this method are:
(1) all synonymous mutations are neutral, i.e., they do not affect the
fitness of the organism,
(2) nonsynoymous mutations can be advantageous, neutral, or
deleterious,
(3) nonsynonymous mutations that are advantageous will undergo
fixation in a population much more rapidly than neutral
mutations.
If advantageous selection plays a major role in the evolution of a
protein, then the rate of nonsynonymous substitution should
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exceed the rate of synonymous substitution.
If positive selection predominates, then KA/KS >
1
If neutrality predominates, then KA/KS << 1
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Prevalence of positive selection
3,595 groups of homologous sequences
In 17 gene groups, the ratio of nonsynonymous
to synonymous substitution was significantly
larger than 1.
Endo T, Ikeo K, Gojobori T. 1996. Large-scale search
for genes on which positive selection may operate. Mol.
Biol. Evol. 13:685-690.
~ 0.45%
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Prevalence of positive selection
7,645 homologous gene groups from human,
chimpanzee, and mouse.
In 6 groups, the ratio of nonsynonymous to
synonymous substitution was significantly
larger than 1, i.e., experienced positive
Darwinian selection (Clark et al. 2003).
~ 0.08%
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The vast majority of
molecular evolution is
neutral.
Change = Equivalence
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Examples of extreme KA/KS values (>>1):
(1) Glycophorin C = a red-cell membrane protein that
serves as the receptor for a Plasmodium falciparum
erythrocyte-binding protein, hence mediating one of P.
falciparum’s invasion pathways in humans. Selective
factor? Malaria.
(2) Granulysin = a protein secreted by cytotoxic T cells
when they attach to infected body cells. It creates
holes in pathogens, such as Mycobacterium
tuberculosi, and destroys them. Granulysin also
induces apoptosis in infected cells. Selective factor?
Tuberculosis.
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Elevated KA/KS ratios are frequently found in sexrelated genes, e.g., genes involved in mating
behavior, fertilization, spermatogenesis,
ejaculation, or sex determination.
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Sperm lysin
Red: Nonsynonymous/Synonymous >> 1
Green: Nonsynonymous/Synonymous ~ 1
Gray: Nonsynonymous/Synonymous << 1
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One of the highest KA/KS
ratios (= 5.15) for a fulllength protein was found
in the 18-kilodalton
protein in the acrosomal
vesicle at the anterior of
the sperm cell of several
abalone species.
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It is thought that sex-related genes
are subject to positive selection for
short periods of time during
speciation as a means of erecting
reproductive barriers that restrict
gene flow between the speciating
populations.
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“A total of 585 of the 13,454 human-chimpanzee
orthologs (4.4%) have observed KA/KS > 1.”
“Simulations show that estimates of KA/KS > 1
would be expected to occur simply by chance in at
least 263 cases, if purifying selection is allowed to
act non-uniformly across genes.”
583  263
100  2.4%
13,454
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Methodological caveats:
(1) The KA/KS test can only detect
positive selection if the proportion of
nonsynonymous substitutions that are
adaptive is >70%.
(2) The KA/KS test can only detect
positive selection if it occurred recently.
(3) The KA/KS test can only detect
positive selection if there are few
reversals (e.g., A to T to A).
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In the KA/KS test we assumed that all
synonymous changes are neutral.
It is possible, however, that not all
synonymous changes are neutral.
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For example, the fitness effects of
synonymous and nonsynonymous
mutations were experimentally shown to
exhibit almost identical distributions in
two protein-coding genes of Salmonella
typhimurium (Lind et al. 2010).
In other words, a synonymous mutation
was as likely to be deleterious as a
nonsynonymous one.
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What is the proportion of synonymous mutations by codon
position?
First codon position
Second codon position
Third codon position
=
=
=
6%
0%
69%
What is the proportion of neutral mutations by codon position?
First codon position
Second codon position
Third codon position
=
=
=
21%
7%
42%
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What is the proportion of synonymous mutations by codon
position?
Second codon position
Third codon position
=
=
0%
69%
What is the proportion of neutral mutations by codon position?
Second codon position
Third codon position
=
=
7%
42%
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What is the proportion of synonymous mutations by codon
position?
Second codon position
Third codon position
=
=
0%
69%
What is the proportion of neutral mutations by codon position?
Second codon position
Third codon position
=
=
7%
42%
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Homoplasy = A structural
resemblance that is due to
parallelism or convergent
evolution, rather than to
common ancestry.
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Are the horns homologous or homoplastic structures?
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Hair
Bone
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Pisciformy
(fish shape)
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Myrmecophagy
(ant-eating)
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Active flight has evolved at least
four times (in insects, pterosaurs,
birds, and bats).
Bioaerial locomotion
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Evolution of
lysozymes
in
ruminants,
langurs
&
hoatzins
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Foregut fermenters are
not herbivores, they are
bacteriovores!
Food for bacteria
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Foregut fermentation has arisen
independently at least three times in
the evolution of placental mammals,
at least once in marsupials, and at
least once in birds.
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Ruminants (e.g., cows, deer, sheep, giraffes)
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Colobine monkeys
(e.g., langurs)
Colobus guereza
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Hoatzin (pronouced Watson), an enigmatic South
American bird (most probably related to the cuckoos).
Opisthocomus hoazin
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Choloepus didactylus
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Quokka
Setonix brachyurus
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Convergent amino-acid replacements in lysozymes from the foregut of cow and
langur. Only convergent replacements are shown, denoted by a one-letter
abbreviation of the resultant amino acid followed by the position number at
which the replacement occurred.
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Adaptive
replacements
contribute to a better
performance of
lysozyme at low pH
and confer protection
against the
proteolytic activities
in the stomach.
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Position 87
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Position 87
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