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The Alcohol dehydrogenase (Adh) polymorphism in drosophila:

- Alcohol is an external potentially toxic substrate
- Maps to 2:50.1
- Well known and studied
- Most activity is found in the fat body (the liver equivalent


Selective neutrality:

- All genotypes are equally fit
- NS is not preferentially selecting one genotype over the other
- Effective population size and mutation rate are important for balancing and maintaining polymorphisms


Clarke protocol and insecticide resistance:

1. Genetic variation must be shown to exist (2 alleles/allozymes, AdhF and AdhS)
2. Allele frequencies must be described over time in one population or through space across populations
3. Demonstrate phenotypic diversity among genotypes for an aspect of molecular function
4. Knowing the function of the gene product, the functional difference between the products of the alleles and the ecology of the organism, we should be able to postulate a relevant, discriminatory selective agent.


AdhF and AdhS

- Two alleles AdhF and AdhS
- Due to the thermostability of the allozymes and their ability to move through a protein gel electrophoresis
- DNA sequencing revealed variation within the AdhF and AdhS allelic class


F/S amino acid replacement effects what?

- Adh-S is lysine 192, a positive amino acid
- Adh-F threaonine 192, a neutral amino acid
- This is the difference in electrophoretic mobility.
- Is one fitter than the other?


There is a relationship between AdhS frequency and latitude:

- There has been a decrease in AdhS frequency as you move away from the equator


Geographical surveys detected a cline on five continents:

- Adhs fequency decreased moved from the equator
- An association with AdhS allele frequency and temperature in wineries


ADH activity and substrates:

- There are a variety of alcohols in the drosophila environment
- Adh-F has a greater specific activity on primary alcohols like ethanol (it metabolises faster than S)
- Adhs has a higher relatve specificity to activity on secondary alcohols (eg, isopropanol)


Primary alcohol:

- Gets converted to aldegyde with NAD is reduced to NADH



- Is converted to acetaldehyde with NAD being reduced to NADH
- Acetaldehyde is further metabolised into acetic acid (which is toxic)
- Build up of acetaldehyde results in mutagenesis of DNA


Acetic acid is an energy source:

- Short term and longer term


Isopropanol is converted into acetone

- This is converted with AdhS to a non-toxic compound


ADH activity and temperature:

- ADH-S is more thermostable in extremely high temperatures (40degrees plus)
- At 40 degrees the flies are sterile, so this is not a realistic advantage
- At lower temperatures the reverse may be true


ADH is required for:

- The utilisation and detoxification of ethanol in larvae and adults


Drosophila are found in a range of environments:

- Temperature
- Type of alcohol
- Alcohol concentrations