Evolution of individual genes in humans
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Evolution of individual genes in humans
Are there any examples of genes that are actively evolving in humans (but which are static in other primates)?
If so, how do we distinguish genes that are under POSITIVE SELECTION from those that are under PURIFYING SELECTION?
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Four papers to read:
1. Balter, M. 2005. Are human brains still evolving? SCIENCE 309:1662 - 1663.
2. Evans, P.D. et al. 2004. Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size. Human Molecular Genetics 13: 1139-1145.
3. Vallender, E.J. and B.T. Lahn. 2004. Positive selection on the human genome. Human Molecular Genetics 13: R245-R254.
4. Evans, P.D. et al. 2005. Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. SCIENCE 309: 1717-1720.
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The traditional way of determining whether a gene is under
PURIFYING SELECTION (NEGATIVE SELECTION)
or
POSITIVE SELECTION (ACCELERATING EVOLUTION)
Ratio of Synonymous (Ks) vs Non-synonymous (Ka) substitutionsin a comparison between species or races or populations
Ka/Ks
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Ks = frequency of synonymous substitutions, i.e.,
the ratio of synonymous substitutions per synonymous site, e.g.,
Leu (L) --> Leu CTT --> CTA, TTA --> TTG, etc
Cys (C) --> Cys TGT --> TGC
Arg (R) --> Arg (R) CGG --> AGG
Definitions of Ka and Ks and Ka/Ks
Synonymous substitutions are not subject to Natural Selection
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Ka = frequency of non-synonymous substitutions, i.e.,
the ratio of nonsynonymous substitutions per nonsynonymous site, e.g.,
-- any nucleotide substitution that causes an amino acid substitution
Val (V) - Leu (L) GTT --> CTTVal (V) - Glu (E) GTA --> GAAThr (T) - Pro (P) ACC --> CCCLeu (L) - Phe (F) CUU --> UUUSer (S) - Arg (R) AGC --> AGA
Non-synonymous substitutions are subject to Natural Selection
- i.e., they are usually deleterious and thus they are seen much more rarely than synonymous substitutions
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What the Ka/Ks ratio means
Ka/Ks = 1.0 Neutral evolution
Ka/Ks < 1.0 Purifying selection (negative selection)
-- the typical form of selection for all life
Ka/Ks > 1.0 Positive Selection (accelerating evolution)
What this means
Non-synonymous substnsare selected against
At least some non-synonymoussubstns are selected for
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Most genes are under purifying selection.Apolipoprotein E appears to be an exception
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Example calculations from Table 3.3
Human/Rabbit -globin: Ka/Ks = 0.015/0.294 = 0.051
Human/Rabbit Apo E: Ka/Ks = 0.114/0.108 = 1.06
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Ka/Ks ratios show positive selection within primate lineage
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Some “controls” to showprimate-specificand human-specificadaptive (accelerated)evolution of MCPH
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Sliding window profile of Ka/Ks in MCPH gene from differentgroups of organisms to highlight primate-specific accelerated evolution
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+ 33 more, including ASPM and Microcephalin and BRCA1
Vallender and Lahn. 2004. Positive selection on the human genome. Human Molecular Genetics 13: R245-R254.
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