Chapter 5.  Mendelian Genetics in Populations I:  Selection and Mutation as Mechanisms of Evolution

• A definition of evolution:  change in allele frequencies in a population.  .
• The Hardy-Weinberg Principle
• Addresses allele and genotype frequencies - caution: don't confuse these concepts with genotype frequencies resulting from a cross or breeding experiment (e.g. mono hybrid cross) in genetics.
• This is a null model - it specifies that allele and genotype frequencies will not change simply as a consequence of meiosis and fertilization.
• Conditions for the Hardy-Weinberg principle to apply:
1. There is no selection
2. There is no mutation
3. There is no migration
4. Chance events do not affect reproduction and survival
5. Mating is at random
• If these conditions apply, then the Hardy-Weinberg principle predicts two things:
1. Allele frequencies will not change from generation to generation.  That is, evolution will not occur.
2. If allele frequencies are p and q, then genotype frequencies will equal p², 2pq, q².
• The predictions can be tested in a real population.  If the predictions are not met, then one or more of the conditions must be false, and the population is evolving.
• Selection changes allele frequencies.
• Natural selection occurs if individuals with different genotypes have different reproductive success (fitness).  This can be due to differential survival to age of reproduction and/or differential reproduction of surviving individuals.
• The Hardy-Weinberg model can be modified to explicitly include selection (Box 5.3 - note new term w, fitness).  If we know the strength of selection we can predict how long it will take for one allele to replace another (Fig. 5.10).
• Some aplications of this model:
• Alcohol dehydrogenase genes in Drosophila populations (experiment by Cavenor and Clegg, Fig. 5.11).
• The Delta32 allele - how long would it take for it to increase in frequency in the human population?  The answer depend on its initial frequency and on the strength of selection (Fig. 5.13).
• Patterns of selection
• In the simplest form of selection, there are two alleles at a locus, one is "more fit" than the other, given enough time one allele replaces the other (p=1.0, q=0, fixation has occurred).  But there are complications:
• Dominance relationships affect rate of evolution (allele substitution).  If recessive allele is infrequent, natural selection will proceed slower than if it is common.  See Damson's experiment with the flour beetles (Fig. 5.14) and the mathematical demonstration of this on p. 131).
• If heterozygotes are more fit than homozygotes, then natural selection will produce equilibrium allele frequencies, and fixation will not occur.  Two examples: Mukai and Burdick with Drosophila (Fig 5.16) and Sickle Cell Anemia.
• If heterozygotes are less fit than homozygotes, then natural selection will fix one allele or the other, depending on which is initially more frequent. Example: Foster et al., Drosophila with compound chromosomes, Fig. 5.17.
• Frequency-dependent selection: if the rare genotype is more fit than the common genotype, then natural selection will produce an equilibrium allele frequency. Example: Hori's "left-handed" and "right-handed" fish, Fig. 5.20).  Frequency-dependent sleection can also explain the maintenance of 50/50 sex ratios.
• Mutation can change allele frequencies, but not very rapidly: "Mutation by itself is not a potent force of evolution".
• Fig 5.22 and the model in Box 5.9 demonstrate this (I will work an example).
• Mutation-selection balance can result in equilibrium allele frequencies, as selection removes from the population the alleles that mutation produces.
• Mutation-selection balance models and heterozygote superiority models can be used to study genetically based diseases.  Two examples: spinal muscular atrophy and cystic fibrosis.
• A more interesting question: does mutation rate limit the rate of natural selection?