Introduction
McVicker et al. used a different approach for detecting
natural selection in the human genome than any that we discussed in
lecture. Specifically, they
Used a hidden Markov model to identify genome segments that are
highly conserved across placental mammals. Some of the segments
are in exons, and some lie outside exons.
Compared the amount of nucleotide sequence diversity (within
humans) and the amount of nucleotide sequence divergence (between humans
and chimps, humans and macaques, and humans and dogs) at the 10 percent
of sites closest to the conserved segments with the diversity and
divergence at the 50 percent of sites that were farthest away.
Compared sequence divergence along the branch leading to humans
with divergence along the branch leading to chimps and the branch
leading to macaques.
Here are figures taken from the paper that illustrate the main
patterns.
Diversity and divergence in the human genome
(from McVicker et al. 2009)
Divergence along the branch leading to humans
(black), to chimps (red), and to macaques (blue) as a function of
recombination distance to a conserved segment and scaled to the
divergence observed at the closest distance. (from McVicker et
al. 2009)
Conclusions in McVicker et al.
McVicker et al. (2009) conclude that
[O]ur analyses reveal a dominant role for selection in shaping
genomic patterns of diversity and divergence
Questions
As with Project #2, I am not asking you to analyze any data or run
any simulations. I’m asking that you apply what you’ve learned about
drift, selection, and evolution at the nucleotide sequence level to
answer several questions related to the analyses they present and the
conclusions that they draw.
What type of selection would explain nucleotide sequence
conservation (i.e., lack of variation) in those genome segments where it
is observed?
How might focusing on sequences that are conserved affect the
conclusions that McVicker et al. (2009) reach?
Why would the amount of divergence and diversity at (presumably
neutral) sites depend on whether they are close to conserved segments or
distant from them?
What evidence do the data provide that the SNPs identified as
neutral are evolving in a way that is effectively neutral?
Are the patterns McVicker et al. found consistent with my claim
that natural selection is primarily purifying? http://darwin.eeb.uconn.edu/eeb348-notes/molevol-patterns.html#revising-the-neutral-theory
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