Darwin Evolutionary interesting

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Teaching Evolution with Examples from Genomics and Medicine Greg Wray Department of Biology, Duke University gwray@duke.edu

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Resources Download from: www.biology.duke.edu/wraylab/resources/ • This presentation (.ppt) • Common misconceptions about evolution (.pdf) • Background readings (.pdf)

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BIO 047 Biology of Dinosaurs (75-100 students) Audience: non-science majors What I teach Most students not willingly enrolled in a science course Most are at about same level as high school AP Biology

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Some challenges in teaching evolution Making evolution believable Opposition based on religious faith Misconceptions about basic concepts of evolution Making evolution real Concepts are abstract Processes are not directly observable Making evolution relevant and interesting Most examples in textbooks are esoteric or negative Processes unfold over very long time scales

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A problem facing teachers Motivating students to engage the material The traditional approach Follow in the intellectual footsteps of Charles Darwin Use biological diversity as a motivator

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A problem facing teachers Motivating students to engage the material The traditional approach Follow in the intellectual footsteps of Charles Darwin Use biological diversity as a motivator Problem with the traditional approach Relatively few students find this a compelling motivation Many conclude evolution is neither relevant nor interesting

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Two useful strategies

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Examples of evolution in action Examples found in most text-books Darwin’s finches Pepper moths Antibiotic resistance Examples students find more interesting Human health Human evolution

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Outline Genomics and what we can learn from it Evolution of resistance to malaria Evolution and major public health concerns

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Outline Genomics and what we can learn from it Evolution of resistance to malaria Evolution and major public health concerns

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Genomics Genome = totality of an organism’s genetic information Usually DNA (nuclear + mitochondrial + chloroplast) RNA for some viruses Only recently possible to fully sequence human genome Extensive / transformative applications for healthcare Also informative for understanding human evolution And both: evolutionary perspective aids medical research

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Push by NIH to sequence many genomes 2000 Draft sequence of human genome 2002 Draft sequence of mouse genome 2005 Draft sequence of chimpanzee genome 20?? Rhesus macaque, gorilla, organgutan, lemur, more

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Drawing on examples from evolutionary genomics Understanding the evolutionary history of humans Compare human and chimpanzee genomes to: 1 Trace patterns of human ancestry and migration 2 Identify genes that contribute to uniquely human traits Michael Neugebauer

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Drawing on examples from medical genomics Biomedical applications of evolutionary genomics: Compare human and chimpanzee genomes to: 1 Mapping genetic basis for human disease 2 Identify genes that can be used for diagnosis or therapy

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Outline Genomics and what we can learn from it Evolution of resistance to malaria Evolution and major public health concerns

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Pathogens evolve quickly Antibiotic resistance Multidrug resistant tuberculosis (and others): huge problem All nosocomial infections: >20,000 deaths/year in the US Evasion of immune surveillance New strains of influenza every few years Influenza infections alone: >35,000 deaths/year in the US Graphic examples of evolution in action, but not happy ones

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The motivating question Can human populations adapt to presence of pathogens? Antibiotic resistance and evasion of immune surveillance provide clear evidence that pathogens evolve quickly.

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A classic example Sickle-cell anemia: hemoglobin B gene (HBB) Aa heterozygoes partially protected against malaria But aa homozygotes suffer adverse health effects Heterozygote advantage -- but only where malaria is present See: anthro.palomar.edu/synthetic/synth_4.htm

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Several other genes influence resistance to malaria Duffy gene (FY) FY*0/FY*0 homozygoes almost completely protected FY*0/FY*N heterozygoes partially protected No adverse health consequences for any genotype Mutation specifically eliminates expression in red blood cells And there are others: NOS2A, HLA-DRB1 Glucose-6-phosphate dehydrogenase gene (G6PD) Lack of G6PD is the most common enzyme deficiency Increase oxidative stress in red blood cells Results in neonatal jaundice and anemia But confers some resistance to infection

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Lessons from malaria Natural selection operates on humans This is evident even over modest time scales Mutations are not always bad Negative connotation, but mutations can be good Different mutations can contribute to same adaptation Often, several ways to achieve same outcome Evolution can have a predictable course Understand geographic distribution and fate of mutations

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Outline Genomics and what we can learn from it Evolution of resistance to malaria Evolution and major public health concerns

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What are the biggest public health concerns? Thus, the chimpanzee genome holds important clues to understanding the genetic basis for these diseases in humans. Heart disease Diabetes Infectious disease Cancer Obesity Stroke Neurodegenerative disease

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The motivating question Heart disease, diabetes, stroke, and obesity all have a genetic basis, and all are common diseases. Why are such clearly maladaptive alleles common?

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The answer is also evolutionary “Thrifty genes” hypothesis, part 1 Prior to modern civilization, it was helpful to crave nutrients Especially: salt, sugar, and fat It was useful to eat a lot of them when food was available Why? These nutrients are limiting for growth and physiology Alleles that encouraged craving/eating them were adaptive

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“Thrifty genes” hypothesis, part 2 Fast-forward to the 21st century and affluent society We still crave salt, sugar, and fat But these nutrients are superabundant in our environment Our genetic make-up is “tuned” to a different environment Too much fat --> obesity and heart disease Too much sugar --> diabetes Too much salt --> high blood pressure, stroke The answer is also evolutionary

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Solutions also come from evolutionary analyses Mutations in specific genes have been identified affecting: Heart disease: MMP3, F7, LGALS2, GCLM Hypertension: PTGIS, AGT, CYP3A5, NOS3 Outcome of infections: TNFA, IL4, HLA-DRB1 Mental health: MAOA, AVPR1A, PDYN Diabetes: TCF1, OAS1, IL6, HLA-DQB1 See: www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM Two sources of information: Genetic differences between humans and chimpanzees Genetic differences among humans

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Lessons from Example Fitness is always measured relative to the environment Same allele can be beneficial or harmful, depending Historical patterns of selection can have a huge impact Have caused enormous health problems (and dollar costs) Evolution can provide insights into the human condition Explains a puzzling and prominent health problem Evolution can also provide practical solutions Comparisons of genome sequences can pinpoint causes