Null hypothesis

1. According to the scientific method, we formulate and “test” a null hypothesis Null hypothesis: the neutral theory Null hypothesis

2. Lewontin and Hubby demonstrated that there was far more variation than we expected using allozymes. The theory of the day was that balancing selection must be maintaining this polymorphism This suggested that selection was ubiquitous, and that beneficial mutations must be common Kimura proposed an alternative: the neutral theory Historical context

3. Most mutations are deleterious and eliminated from the population Rare beneficial mutations arise and are fixed virtually instantaneously Most segregating variation is selectively neutral Stochastic forces such as genetic drift are responsible for much of evolutionary change, with adaptation playing a minor role The neutral theory

4. Drosophila melanogaster, the common fruit fly, is found throughout the world and feeds on rotten fruit There is genetic variation for the efficiency of alcohol metabolism in Drosophila Alcohol metabolism in the fly is controlled by many genes, of which one is Alcohol dehydrogenase There are two alleles of Alcohol dehydrogenase, Fast and Slow Natural history of Drosophila and alcohol

5. Just as we can see variation in a trait and variation in genotypes (allele frequencies), we can see variation in the DNA sequence of individual copies of an allele. Variation in alcohol metabolism, the trait Variation in the frequency of the Fast allele Variation between individual copies of Fast (DNA sequence) Variation and selection at many levels: alcohol metabolism in Drosophila

6. L o c a l e L a t i t u d e F r e q u e n c y o f A d h - F a l l e l e M E 4 4 . 3 6 5 5 % V T 4 3 . 4 7 5 5 % M A 4 2 . 3 0 5 8 % C T 4 1 . 3 4 6 0 % N J 4 0 . 2 1 6 3 % M D 3 9 . 0 0 6 6 % N C 3 5 . 4 6 7 0 % F L 1 3 0 . 2 0 8 2 % F L 2 2 7 . 2 8 8 8 % F L 3 2 5 . 2 7 9 0 % U. S. variation in the frequency of Alcohol dehydrogenase Fast allele

7. Regression of latitude and Adh-F frequency:hypothesis test 1.0 0.9 0.8 Adh-F frequency 0.7 0.6 0.5 20 30 40 50 Latitude

8. Polymorphism is present throughout the cline (and, indeed, throughout the world) What else do we notice about Alcohol dehydrogenase?

9. Selection changes the gene frequency in populations What does selection actually do genetically?

10. Biston betularia Biston imaginaria 123456789 B.b. catcataag B.b. catcataat B.b. catcataag B.i. tatcataag Within and between species variation

11. The null hypothesis: In the absence of selection, there will be a characteristic association between levels of within and between species variation. The test: compares levels of within and between species variation for the gene of interest (here, Adh) with another locus which is evolving without selection. The HKA test Hudson, Kreitman and Aguadé 1987

12. Within Between Ratio • Adh 34 43 0.8 • neutral locus 30 77 0.4 HKA example: selection in Alcohol dehydrogenase

13. Between species Within species Correlation of within and between species variation Correlation of within and between species variation neutral loci selected gene (Adh)

14. The outcome of selection is a change in gene frequencies in the population (Dq!) It is Dq that causes the changes in phenotype In natural populations, we frequently do not know the agent of selection and/or have not had the opportunity to observe the population over a long enough period of time. Other forces such as genetic drift can also change gene frequencies Detection of selection can be difficult We can detect selection at many levels: the trait, the genotype, and the DNA sequence The neutral theory explains most of what we see Main points