BIOB 272 1st EditionFinal Exam Study Guide Lectures: 23-39Lecture 23 and 24 (March 23 and 26)Genealogies, genetic variation and molecular evolution Know how genetic variation in populations is detected and why knowledge of genetic variation is important for understanding the evolution of populations - Variation within and between populations is the raw material for adaptation and speciation- Patterns of genetic variation reveal past evolutionary processes- Genetic marker loci are useful for studying current ecology of populations (including humans and their diseases)- How do we detect genetic variation?1. Phenotype (back to Mendel)2. Chromosomes (1930s) Polyploidy/ Rearrangements3. Protein electrophoresis (1960’s)4. DNA fragment electrophoresis (1980s)Polymerase Chain Reaction (PCR) and Microsatellites & other DNA-based markers5. DNA sequencing (1990s – present)- 5b. (2005-present) Next-generation sequencing –ultra highthroughout sequencing of genomes- DNA Fragment Polymorphisms: Polymerase Chain Reaction (PCR) - a method for makingmany copies of a specific segment of DNAo Microsatellites: Many alleles per locus, lots of loci  Can get DNA from a tiny sample  Used in forensics & many other applied applications because shows a sort of “fingerprint”- everyone’s is differento CODIS: The standard human DNA forensic testing set used by the FBI comprises 13 microsatellite loci, each of which is located on a separate chromosome.  Probability of any two individuals showing the same pattern at all 13 loci is <1 in 10^15Appreciate how functional constraint (natural selection) varies across different regions of the genome and what impact this might have on patterns of genetic variation within and between species - DNA Sequence Variationo Sequencing of genes reveals even more variationo Variants typically single nucleotide polymorphisms(SNPs)= single position in a genome that is varianto Some variation is neutral, some is under selection(variant)o Different regions of the genome evolve at differentrates. Non-coding sites, introns and intergenicregions evolve relatively fast.o Introns evolve more rapidly between species than exons due to less functional constraint Exons= high conservation, low divergence Introns= Low conservation, high divergenceo Next Generation sequencing makes sequencing projects possible that weren’t even imagined even 5 years agoo The 3rd position of the codon evolves neutrally Know the central predictions of the neutral theory and the general assumptions that the model is based on - Neutral Theory of Molecular Evolution:Most evolutionary change at the molecularlevel is driven by random genetic drift ratherthan natural selection.– Most mutations are deleterious and removed– Positive selection is relatively rare (but does occur)– Remaining genetic are neutral or nearly neutral and thus do not influence fitness– DOES NOT suggest that random drift explains all evolutionary change– The neutral theory states that random processes dominate evolution at the level of the DNA and proteins and most evolution at the molecular level would then be nonadaptive. o That is most observed nucleotide polymorphisms within populations and substitutions between species are neutral and do not impact fitnessUnderstand how effective population size and mutation rate are related and how each influences the rate of genetic change- Rate of Genetic Change:input of new mutation X prob. mutation will fix in pop– The input of new mutations: 2Nµ– Mutation rate µ = number new mutations per allele per gen.Number of alleles in the population = 2N– Probability of fixation = 1/2N= 2Nµ x 1/2N = µ (the mutation rate)Understand what is meant by a molecular clock, what kind of information they require, and howthey are used in evolutionary biology - Applications of the neutral theory:Null model (like H-W) used to detect nonneutralevolution in DNA sequences=Suggests that genetic divergence canbe used to infer the timing of evolutionary events, that is, divergence provides a molecular clock.– Molecular Clocks:using the linear accumulation of substitutions over time to infer when evolutionary events occurred.o Requires:1. Genetic information (divergence between species)2. Calibration of substitution rate per year (usually fossilbased)o Can graph to show linear accumulation substitutions over time- Mammalian Diversification Example:o Asteroid hit earth millions of years ago=Mammals radiated in response over the dinosaurs= dinosaurs went extincto Molecular clocks used to estimate find diversification eventso Show using a phylogeny to show a summary of estimated from many genetic loci=Show how certain copies of a gene are relatedto other species’ copy of that geneo There are two peaks in mammalian diversification rateso Most of diversification of mammals happened before dinosaurs went extinctUnderstand what is meant by the term genealogy - A line of descent traced continuously from an ancestor.- Individual genetic loci (genes) have their own phylogeny =genealogy that dates back to a MRCA (most recent common ancestor) Understand the basic principles behind coalescent theory and how population size impacts the coalescent process - Coalescent:is a stochastic process that relates the probability of shared ancestry in a collection of individuals (or genes, or alleles) sampled from a given population.- Gene Tree:the branchedgenealogical lineage ofhomologous alleles that tracestheir evolution back to a singleancestral allele.*Alleles in population coalesce to a common ancestorAppreciate why genealogical coalescent times vary across the genome and how this variation might impact the use of individual genealogies to reconstruct species relationships (species trees)- Eventually all lineages coalesce to a single lineage=MRCA of the sample- Rate in which lineages coalesce depends on the size of the populationo Larger the population (more parents to choose from) the slower the rate= big population (Ne) have deep coalescent timeso The coalescent times to MRCA vary across the genomeo Average time to MRCA is 4Ne generation = much of this variation is stochastic and essentially due to the same random sampling process that leads to genetic driftWhat is the average time to MRCA across genes in human populations?A) 5,000 years B) 100,000 years C) 800,000 years D) 3,000,000 yearsanswer: C) 800,000 = 4*10,000*20-20 years per generation-Long term Ne in humans is about 10,000 -4 is