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Detection of the footprint of natural selection in the genome Lorena Blanco Fernández A brief history of natural selection • Darwin began formulating his theory of natural selection in the late 1860 • Wallace help Darwin in his studies • The descent of species from common ancestors were well accepted • Natural selection took a harder time to be accept Kinds of selection Signatures of selection • High proportion of function altering mutations Time Prolonged period can increase the fixation rate of beneficial function-altering mutations • Reduction in genetic diversity The selected allele rises to fixation, bringing with it closely linked variants • High-frequency derived alleles In a selective sweep, derived alleles linked to the beneficial allele can hitchhike to high frequency Kelley, J.(2007) Signatures of selection • Differences between populations Positive selection may change the frequency of an allele in one population but not in another • Long haplotypes Selected allele may rise in prevalence rapidly enough that recombination does not break down the association with alleles at nearby loci. Methods for detect microevolution selection Linkage disequilibrium Frequency spectrum Detect - Positive - Balancing Extended haplotype homozygosis (EHH). statistical test Detect - Partial or incomplete selective sweep - Balancing Vitti, J.(2013) I M E T Tajima’s D statistical test Based on long haplotypes T I M E Based on high frequency derived alleles Methods for detect microevolution selection Population differentiation Allele frequencies I M E Wright’s fixation index (Fst) Composite methods Combine the results of one or a few tests for many variants Combine the results of many tests at a single site T Fst Detect: - Positive - Negative Vitti, J.(2013) XP-EHH IHS (kind of LD) Gene under selection LCT Traces of selection • High Fst values for the 99 flanking DNA sites on LCT locus. • REHH was estimated to be extremely high • Selective sweep acting since 2000-20000 years ago Kelley, J.(2007) Bibliography • Vitti, J. J., Grossman, S. R., & Sabeti, P. C. (2013). Detecting natural selection in genomic data. Annual Review of Genetics, 47, 97–120. http://doi.org/10.1146/annurev-genet-111212-133526 • Kelley, J. L., & Swanson, W. J. (2008). Positive selection in the human genome: from genome scans to biological significance. Annual Review of Genomics and Human Genetics, 9, 143–160. http://doi.org/10.1146/annurev.genom.9.081307.164411 • Ridley, M. (2004). Evolution. Evolution. http://doi.org/10.1007/978-3-0348-6133-5 • Sabeti, P. C., Schaffner, S. F., Fry, B., Lohmueller, J., Varilly, P., Shamovsky, O., … Lander, E. S. (2006). Positive natural selection in the human lineage. Science (New York, N.Y.), 312(5780), 1614–1620. http://doi.org/10.1126/science.1124309 • Oleksyk, T. K., Smith, M. W., & O’Brien, S. J. (2010). Genome-wide scans for footprints of natural selection. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 365(1537), 185–205. http://doi.org/10.1098/rstb.2009.0219 Thanks for your attention!