1. Detection of the footprint of natural selection in the genome
Eliseo Pampín Bello

2. Quintana-Murci, L. , & Clark, A. G. (2013)
Quintana-Murci, L., & Clark, A. G. (2013). Population genetic tools to dissect innate immunity in humans. Nature reviews. Immunology, 13(4), 280.

5. Vitti, J. J. , Grossman, S. R. , & Sabeti, P. C. (2013)
Vitti, J. J., Grossman, S. R., & Sabeti, P. C. (2013). Detecting natural selection in genomic data. Annual review of genetics, 47,

6. Sabeti, P. C. et al. (2006). Positive natural selection in the human lineage. science, 312(5780),

7. High proportion of funcion altering mutations
Comparison of DNA sequence between species
Genetic variants that alter protein function are usually deleterious
Ka/Ks test, relative rate tests, and the McDonald-Kreitman test

8. Reduction in genetic diversity
‘‘Hitchhiking effect’’ leads to a ‘‘selective sweep,’’ which alters the typical pattern of genetic variation in the region
New mutations restore diversity, but firstly appear in low frequency
Tajima’s D, Fu and Li’s D*…
Akey, J. M., & McCoy, R. C. (2017). Selection plays the hand it was dealt: evidence that human adaptation commonly targets standing genetic variation. Genome biology, 18(1), 139.

9. High-frequency derived alleles
New derived alleles typically have lower allele frequencies than ancestral alleles
Linked to the beneficial allele, they can hitchhike to high frequency but they do not reach fixation (incomplete sweep or recombination)
Signature: region containing many high-frequency derived alleles
Fay and Wu’s H

10. Differences between populations
Relatively large differences in allele frequencies between populations may signal a locus that has undergone positive selection

11. Long haplotypes
 LRH, iHS…
Under positive selection, a selected allele may rise in prevalence rapidly enough that recombination does not substantially break down the association with alleles at nearby loci on the ancestral chromosome.
So, big haplotypes which are in high frequency are hallmarks of positive seleciton

12. Examples of traits affected by loci undergoing selection
Bustamante, C. D., et al. (2005). Natural selection on protein-coding genes in the human genome. Nature, 437(7062),

14. LCT
Genetic distribution of lactase persistence matches with the distribution of dairy farming
Excess of rare variants
Large allele-frequency differences among populations: Fst and pexcess.
Common haplotype remains intact over unusually long distances: REHH

15. LCT
Bersaglieri, T., Sabeti, P. C. et al. (2004). Genetic signatures of strong recent positive selection at the lactase gene. The American Journal of Human Genetics, 74(6),

16. LCT
Warinner, C., Hendy, J. et al. (2014). Direct evidence of milk consumption from ancient human dental calculus. Scientific reports, 4.

17. FOXP2
Likelihood ratio to test for constancy of the ratio of amino-acid replacements over nucleotide changes that do not cause amino-acid changes among the evolutionary lineages.
Positive selection or relaxed constrain
Enard, W., Przeworski, M. et al. (2002). Molecular evolution of FOXP2, a gene involved in speech and language. Nature, 418(6900),

18. FOXP2
Then, they sequenced bp covering introns 4, 5 and 6 of FOXP2, in different populations of humans, some chimps and one orangutan.
Two predictions:
sharp excess of rare (low frequency) alleles : Tajima’s D.
Problem: sensitive to population growth
In a recombining locus, more derived alleles at high frequency are expected under the standard neutral model: Fay and Wu’s H.
Robust to this kind of analysis

19. Genome-wide detection of selection
Data from HapMap2
They combined iHS, LRH and XP-EHH
Criteria:
Selected alleles detectable by this tests are likely to be derived, because long-haplotype tests have little power to detect selection on standing (pre-existing) variation; this study focused on derived alleles, as identified by comparison to primate outgroups.
Selected alleles are likely to be highly differentiated between populations, because recent selection is probably a local environmental adaptation; this study, thus, looked for alleles common in only the population(s) under selection.
Selected alleles must have biological effects. On the basis of current knowledge, the study therefore focused on non-synonymous coding SNPs and SNPs in evolutionarily conserved sequences.

20. Genome-wide detection of selection
Sabeti, P. C., Varilly, P. et al. (2007). Genome-wide detection and characterization of positive selection in human populations. Nature, 449(7164),

21. Genome-wide detection of selection
Sabeti, P. C., Varilly, P. et al. (2007). Genome-wide detection and characterization of positive selection in human populations. Nature, 449(7164),

22. References
Akey, J. M., & McCoy, R. C. (2017). Selection plays the hand it was dealt: evidence that human adaptation commonly targets standing genetic variation. Genome biology, 18(1), 139.
Bersaglieri, T., Sabeti, P. C. et al. (2004). Genetic signatures of strong recent positive selection at the lactase gene. The American Journal of Human Genetics, 74(6),
Bustamante, C. D., et al. (2005). Natural selection on protein-coding genes in the human genome. Nature, 437(7062),
Enard, W., Przeworski, M. et al. (2002). Molecular evolution of FOXP2, a gene involved in speech and language. Nature, 418(6900),
Quintana-Murci, L., & Clark, A. G. (2013). Population genetic tools to dissect innate immunity in humans. Nature reviews. Immunology, 13(4), 280.
Sabeti, P. C. et al. (2006). Positive natural selection in the human lineage. science, 312(5780),
Sabeti, P. C., Varilly, P. et al. (2007). Genome-wide detection and characterization of positive selection in human populations. Nature, 449(7164),
Vitti, J. J., Grossman, S. R., & Sabeti, P. C. (2013). Detecting natural selection in genomic data. Annual review of genetics, 47,
Warinner, C., Hendy, J. et al. (2014). Direct evidence of milk consumption from ancient human dental calculus. Scientific reports, 4.