Evolution and Human HealthWhy is evolution important for human health?I. Disease EvolutionEvolution of Antibiotic ResistanceSlide 5Antibiotic ResistomeMechanisms are similar between ancient and recent bacterial strainsMechanisms of antibiotic resistance are ancient in originSlide 9PowerPoint PresentationAntibiotic ResistanceB. Natural Selection and CancerSperm ProductionNatural selection on placentasII. Using Evolution to Predict DiseaseA. New strains of diseaseInfluenzaSlide 18Influenza evolutionInfluenza EvolutionB. Designing Flu vaccinesSlide 22C. Tracking Disease Evolution: Influenza ReassortmentSlide 24Slide 25Slide 26Slide 27III. Evolution of VirulenceA. Virulence: Coincidental EvolutionB. Virulence: Short-sighted EvolutionC. Virulence: Trade-offsTrade-offs: PredictionsIV. Adaptation and the Human EnvironmentHistory of Human EvolutionMyopia (nearsightedness)Breast CancerEvolutionary Explanations for DiseaseOverdominance and diseaseIllnesses that are not…Morning SicknessDarwiniian Medicine: symptoms as adaptationsEvolution and Human HealthWhy is evolution important for human health?1. Pathogen evolutionInfluenza A2. Humans and selectionI. Disease Evolution•What is the evolutionary struggle between humans and pathogens and how does that effect pathogen evolution?–Host immune system places selection on pathogen–Pathogen must evolve counter attacks against host defensesA. Evolution of Antibiotic Resistance1. How do bacteria acquire resistance?–Mutations•Resistance can often occur as point mutation•Rifampin resistance in tuberculosis–Lateral transfer of plasmids–Viral transfer of resistance gene–Scavenging of resistance geneEvolution of Antibiotic Resistance2. Mechanisms of antibiotic resistance1.2.3.4.5.6.Antibiotic ResistomeAntibiotics are naturally produced by bacteria to outcompete other bacteriaBhullar et al. 2012Mechanisms are similar between ancient and recent bacterial strainsControlT = 0T = early log-phaseBhullar et al. 2012Mechanisms of antibiotic resistance are ancient in originLechuguilla cave isolates--~4MYBhullar et al. 2012Evolution of Antibiotic Resistance•Once established, selection favors resistant bacteria•Decreased use of particular antibiotic may result in fewer resistant organisms–However, rate of loss of resistant strains isAntibiotic Resistance~2 million people get an infection in the hospital each year•90,000 die (up from 13,300 in 1992)are resistant to at least one drug used to treat themB. Natural Selection and Cancer•Cancer is the result of disruptions to the cell cycle–Indiscriminant cell proliferation •Natural selection has favored certain defenses but cannot eliminate cancer altogether–Certain adaptations for other functions are co-opted by cancer cellsSperm Production•Faster dividing sperm cells have a fitness advantage–Proteins that increase celldivision in spermatogenesis can lead to cancer in somatic cells -Cancer mutations have a higher fitness from other cells.Natural selection on placentas•Genes that allow cells to build a better placenta are favored by natural selection–Cancer cells can hijack these genes–Aggressive growth–New blood vessel formation –Tumors use blood vessel formation to grow larger.II. Using Evolution to Predict Disease•How can understanding pathogen evolution help us track their spread?•How can we predict new outbreaks of bacteria and viruses?•Example: Flu and the flu vaccine–How can we predict which strains of the flue will be prominent in the next year in order to prepare an effective flu vaccine?A. New strains of disease•How can we use evolution to develop new treatments for disease?–Example: Flu and the flu vaccine –How can we predict which strains of the flu will be prominent in the next year in order to prepare an effective flu vaccine?InfluenzaHemagglutinin (H)Neuraminidase (N)Breaks up sialic acid receptors on cellBinds to sialic acid receptors on cellTaubenberger et al 2004Influenza evolution•No proofreading mechanism in RNA, so very high mutation rate (about a million times faster than human DNA)–100,000-1 million progeny leave infected cell–99% are defective–1,000-10,000 still remain to infect new cellsInfluenza Evolution•Mutations concentrated in genes for hemagglutinin and neuraminidase–Allows the virus to evade the immune systemsurvivingextinctB. Designing Flu vaccines•Antigenic sites are most likely to mutate–Specifically, 18 codon positions under positive selection •HWE strikes again!•See which has the highest mutation rate in the 18 codon positions. –Researches determine which of the current strains is likely to have surviving descendents in the future•Likely the strain with the most mutations in the 18 codons known to be under the positive selection•Accurately able to predict 9 of 11 recent flu seasonsBush et al. 1999C. Tracking Disease Evolution: Influenza Reassortment•10 genes on 8 pieces of RNA•If two different types of flu infect the same cell, their RNA can reassort and daughter viruses have genes from both flu “parents”Swine have been involved in the spread of influenza viruses among different speciesTheir tracheal cells have receptors on the surface that welcome both avian and human strains. • Human cells shut out avian influenzas.This makes the pig a potential mixing vessel for viruses from different species to combine genes (reassortment). This is what we saw in the 2009 H1N1 sequence.Sinha et al. 2009Swine flu of 2009 was more similar to 1918 strain than any recent strain. The evolutionary theory of tracking common lines of descent can show us where the lineages of flu come from and how they can be prevented.•Stronger stabilizing selection (smaller Ka/Ks ratios) on HA and NA in 2009 suggesting a particularly fit new antigen type. Sinha et al. 2009III. Evolution of Virulence•Why are some diseases more virulent (cause more harm) compared to other diseases?–If one evolutionary strategy is favored why don’t all disease-causing organisms converge on it?•Three hypotheses1. Coincidental evolution2. Short-sighted evolution3. Trade-off hypothesisA. Virulence: Coincidental Evolution•The virulence of some pathogens in humans may be accident; there is no direct selection for them in humans•Example:–Claustridium tetanae causes tetanus in humans and can be highly lethal–However C. tetanae is usually a soil bacteria so virulence in humans is likely a byproduct of selection to their soil