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Evolution and disease: outline
How can we use evolutionary ideas to understand
disease, and
vice versa
?
•
Drift and tradeoffs in genetic diseases
•
Host-parasite coevolution: racing the Red Queen
•
Parasite strategies and the evolution of virulence
Genetic diseases
•
the simplest diseases to understand are
single-
factor
, mutations that knock out critical genes in a
metabolic pathway
•
ex: Tay-Sachs, cystic fibrosis, sickle-cell anemia
•
often lethal, or clearly detrimental to fitness; what
maintains these mutations in the population against
obvious selective forces??
–
null model
:
mutation-selection balance
• drift
•
tradeoffs (pleiotropy)
•
gene-by-environment (GxE) interactions
Mutation-selection balance
•
perhaps new mutations are occurring as fast as
they can be eliminated by selection:
mutation-
selection balance
•
we can calculate expected frequencies based on
mutation rate
m
and selection coefficient
s
–
dominant allele, frequency =
m/s
–
recessive allele, frequency = sqrt(
m/s
) (>
m/s
)
•
rates for genetic diseases are (mostly) too high for
mutation-selection balances: we
reject
the null
hypothesis …
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