Overview of Lecture: Microevolution I Read: Text pgs 450-451, ch 22 & 23 Gibbons, A. 2010. Science 13(329):740-742. Bullet Points: • phenotypic & genetic variation within & between populations: • ancestry, genotype, “race” & medicine • the Human Genome Diversity Project – Out of Africa • selection & drift: Non-synonymous & Synonymous base substitutions • ancestral climate & disease risk • are humans still evolving? • Hardy-Weinberg equilibrium – a null model • causes of microevolution • MHC & mate choice • evolution of influenzaNEWS FOCUS HUMAN EVOLUTION: Tracing Evolution's Recent Fingerprints Ann Gibbons, Science, 13 August 2010, 329: 740 – 742 The hunt for the genes that helped humans adapt to new climates, diseases, and diets is exposing how evolution works. Rasmus Nielsen was analyzing the frequency of different mutations in the genomes of Tibetans living at high altitude, searching for adaptations that allow them to thrive in thin air. … two stood apart … they existed in almost all Tibetan highlanders but not in their close relatives, the Han Chinese. … this was a radical example of rapid evolution, with strong natural selection acting on a single gene … the EPAS1 gene that regulates oxygen sensing in humans. One of the mutations … had spread to 90% of all Tibetans in just 4000 years … the most rapid and strongest example of selection known in modern humans All living humans are remarkably similar genetically because we all descended from a small founder population that arose in Africa about 200,000 years ago. As these modern humans moved … out of Africa in the past 80,000 years or so, they evolved genetic differences that helped them adapt to new climates, digest novel foods, and fight off new illnesses and parasites. Sometimes, dramatic new mutations produced those differences. Other times, selection acted on standing variation …individuals vs racial groupings? measured genes vs genes inferred from racial grouping? {is skin color closely correlated w/ ancestry? –does it predict genes at other loci?}Figure 5. Triangular, three-dimensional representation of individual ancestry proportions {from genetic markers} and constitutive pigmentation values (melanin index; on the vertical axis) in self-identified African Americans ( ), Puerto Ricans ( ) & Mexicans ( ). Mexicans ( ) African Americans. ( ) African Caribbeans. ( ) Mexicans. ( ) Puerto Ricans Implications of correlations between skin color and genetic ancestry for biomedical research Parra et al. Nature Genetics 36,S54-S60 (2004) Compare these two “ave African Am.” individuals We studied the relationship between pigmentation and ancestry in {self-identified} populations of mixed ancestry with a wide range of pigmentation and ancestral proportions ( African Americans from Washington, DC; African Caribbeans living in England; Puerto Ricans from New York; Indigenous Mexicans from Guerrero; and Hispanics from San Luis Valley). The strength of the relationship between skin color and ancestry was quite variable … Skin pigmentation is a central element of 'race‘. Imagine guessing ancestry given melanin index valueFOR IMMEDIATE RELEASE FDA News P05-32 June 23, 2005 FDA Approves BiDil Heart Failure Drug for Black Patients The Food and Drug Administration (FDA) approved BiDil (bye-DILL), a drug for the treatment of heart failure in self-identified black patients, representing a step toward the promise of personalized medicine. Randomized trials have been interpreted to show that a combination of vasodilators is more effective in treating heart failure in black persons than in white persons and that angiotensin-converting–enzyme (ACE) inhibitors have little efficacy in blacks. all of the self-identify as ‘black’see 10/15 link: A survey of human evolution}Fig. 1. Individual ancestry and population dendrogram. (A) Regional ancestry inferred with {phlogenetic algorithms that estimate overall genetic (SNPs) similarity }. Each individual is represented by a vertical line; colored segment lengths correspond to his/her ancestry coefficients in up to seven inferred ancestral groups. Population labels were added after ancestry had been estimated; they were used to order the samples in plotting. (B) Maximum likelihood tree of 51 populations. Branches are colored according to continents/regions. * indicates the root of the tree, also where the chimpanzee branch is located. Li et al, 2008Selection will tend to maintain genes that increase reproductive success even if these ... increase disease susceptibility in older age. For example, genetically determined high cytokine {immune sys} response levels may be associated with adverse cardiovascular outcomes in older individuals but may increase reproductive success in young age by conferring resistance to fatal infectious diseases ... {more on “adaptive” theories for aging later}A simple way of detecting selection from comparative genomic data is to calculate the ratio between the rate of nonsynonymous substitutions and the rate of synonymous substitutions (ie, dN/dS). This ratio provides a means of detecting selective pressure: dN/dS = 1 for no selection, {random drift} dN/dS < 1 for purifying selection, and {stable phenotype} dN/dS > 1 for positive selection {changing phenotype}Ding KY, Kullo IJ 2009. continued ...304 (9.0%) loci showed evidence of rapid amino acid evolution. 813 (13.5%) show a paucity of amino acid differences between humans & chimps indicating weak negative selection. The results of analysis of human polymorphism at this scale may help to guide our thinking about human evolution ...Say kids, what time is it? It’s Hardy-Weinberg Time! see C&R sec 23.2If we observe from a sample of data that one outcome (yes, win, head, allele-A, etc) occurs x times out of n possible times (‘Bernoulli trials’) then we say that that outcome has observed probability or relative frequency: p = x / n .Suppose we have two coins ; & we want to test whether they are “fair” (long-term ave = p(h) = 0.5) & independent of each