1. Plant of the day! Pebble plants, Lithops, dwarf xerophytes Aizoaceae
South African
Plants consist of one or more pairs of bulbous leaves – almost no stem
Leaf markings appear to help plant match its background and be less vulnerable to herbivory
Lithops lesliei 1 1

2. Adaptation 2

3. Goals
Understand some top down and bottom up approaches used to identify genes responsible for adaptations
Explain patterns of sequence variation expected with positive and balancing selection
Understand the principles of population genetic tests of selection 3

4. The genetic basis of adaptation
Phenotype to genotype (Top down)
Candidate loci for traits responsible for phenotypic differences
QTL, association mapping
Genotype to phenotype (Bottom up)
Population genetics 4

5. Which locus is likely involved in the change in floral phenotype?
Loci
Loci 1 2 3 4 1 2 3 4 1 3
Selective sweep 4 2 5 5

6. Which locus is likely involved in the divergence in floral phenotype?6 6

7. -May not be the loci in other individuals/environments
Quantitative trait loci (QTL) are regions of the genome associated with the trait in question
-May not be the loci in other individuals/environments
-Statistical issues (sample size, genes of small effect, epistasis)
-Can be large regions of a chromosome (further mapping in region needed)
-Can't perform in all species
Rodney Mauricio 2001 7

8. Association mapping
Associations between markers (SNPs) and phenotypes in natural populations
Can find precise mutation responsible
No crossing required
False associations due to population structure
Large sample size, many markers needed (if no candidate loci)
allele1 allele2
SNP1 100% 0%
SNP2 50% 50%
allele1 allele2
SNP1 0% %
SNP2 50% 50% 8

9. The genetic basis of adaptation
Phenotype to genotype (Top down)
Candidate loci for traits responsible for phenotypic differences
QTL, association mapping
Genotype to phenotype (Bottom up)
Population genetics 9

10. Neutral Theory Kimura (1968, 1983)
Motoo Kimura ( )
Ph.D. University of Wisconsin in 1956
Under James Crow
Kimura argued that the great majority of evolutionary changes at the molecular level are not caused by selection but by random genetic drift. 10

11. Neutral Theory: Evidence
Molecular evolution takes place at a relatively constant rate, simply through random genetic drift, enough to provide a “molecular clock” of evolution. 11

12. Selection-Neutral Debate
Kimura’s work spawned a heated debate on the relative importance of neutral evolution (genetic drift) versus genetic variation that is a result of natural selection. 12

13. Neutral Theory
Now considered the “null model” against which evidence for selection should be tested 13

14. Detecting Natural Selection
There are many statistical tests for detecting Natural selection
The approach is to test for deviations from a null neutral model (where genetic variation arises only from genetic drift)
Null hypothesis: Neutral, no selection
Deviation from Neutral: selection
Inferences regarding selection provide a powerful tool for the prediction of genes underlying traits of ecological or economic value 14

15. The effects of selection on the genome
Directional selection
Best allele(s) sweep to fixation
Loss of variation
Change in frequency distribution of polymorphisms
Increase in linkage disequilibrium around the site 15

16. The effects of selection on the genome
Balancing selection
Maintains variation that otherwise would be lost to drift
Heterozygote advantage, frequency dependent selection, fluctuating selection, (divergent selection) 16

17. A beneficial allele arises
Variants with this allele rapidly spread through the species
Genetic diversity is reduced around this adaptive locus
ancestral
After selection 17 17

18. Recombination, mutation Initial frequency
Time
Strength of selection
Recombination, mutation
Initial frequency
Chance of detecting positive selection depends on: 18 18

19. Methods for Detecting Selection:
A. MacDonald-Kreitman Type Tests
B. Site Frequency Spectrum Approaches
C. Linkage Disequilibrium (LD) and Haplotype Structure
D. Population Differentiation: Lewontin-Krakauer Methods
These tests could be applied to single genes, or across the whole genome. 19

20. Codon Bias in Amino Acid Substitutions
Synonymous
substitutions:
Mutations that do not cause
amino acid change (usually
3rd position)
“silent substitutions”
Nonsynonymous
Mutations that cause amino
acid change (1st, 2nd position)
“replacement substitutions” 20

21. A. MacDonald-Kreitman Type Tests
Ka/Ks Test
Nonsynonymous substitutions Ka
Synonymous substitutions Ks
Need coding sequence (sequence that codes proteins)
Ks is used here as the “control”, proxy for neutral evolution so Ka/Ks = neutral evolution
A larger nonsynonymous substitution rate (Ka) than synonymous (Ks) is used as an indication of selection (Ka/Ks >1)
Ka/Ks < 1 ?
> 1 21

22. dN vs. dS for pairwise sequence comparisons in Physalis (nightshade)
Richman A D , Kohn J R PNAS 1999;96:
©1999 by National Academy of Sciences 22

23. B. Site Frequency Spectrum
Selection affects the distribution of alleles within populations
Method examines site frequency spectrum and compares to neutral expectations
Could be applied to a single locus. Now used often for genomic scans for selective sweeps
Domestication alleles (corn, rice) 23

24. 24

25. Nucleotide diversity (π) in maize and teosinte for teosinte glume architecture (tga1). Tajima's D-statistic and HKA tests for non-neutral evolution are shown (Nature 436, (4 August 2005)

26. C. Linkage Disequilibrium (LD)
The nonrandom association of alleles from different loci, where they are found more or less frequently together than expected
Selection increases levels of linkage disequilibrium during the process of selection 26

27. D. Population Differentiation: Lewontin-Krakauer Methods
Selection would often increase the degree of genetic distance between populations
Compute pairwise genetic distances (FST) for many loci between populations
When a locus shows extraordinary levels of genetic distance relative to other loci, this locus is a candidate for positive selection 27

28. Example of Fst scan in sunflowercM 28