Genome 561 Course Page

Genome Sciences 561: Molecular Population Genetics and Evolution.

Winter Quarter 2020 (first 5 weeks) T Th 9:00-10:20

Instructor: Kelley Harris (harriske@uw.edu)

Course Page: https://sites.google.com/site/harriskelley/genome-561-course-page

Office hours: Friday 2 PM - 3 PM Foege 420C or by appointment.

If anyone is planning to come to office hours but does not have Foege Card access, please email ahead of time so we can meet in the Foege lobby at 2 PM.

This course will discuss the history and practice of research in molecular evolution. The aim is to introduce population genetic theory as a lens for the interpretation of modern genomic datasets. By the end of the course, you should have learned to appreciate the power of simple population genetic models, and you should also know the basic differences between idealized models and the data you might encounter in real life.

During each class, I will introduce a set of evolutionary concepts and summarize key research papers where these concepts were discovered and/or applied. Students are expected to ask questions during lecture and participate in discussion of the concepts and debates that are presented. During the first two weeks, you will be assigned problem sets that are designed to develop your intuition so you’ll be able to get more out of the papers you read in the course.

Paper reading assignments and discussions: At the end of many lectures, you will be assigned one or more papers to read. For each assigned paper, I will provide short answer questions to guide you through some of its most important points. Your assignment is to type up brief responses to these questions (max 3-5 sentences per question) and bring a hard copy to class on the assignment due date. You will receive pass/fail credit for turning in answers to all questions. Students will discuss the questions and answers in small groups and as a class.

Problem sets: Problem sets will be a combination of simple calculations, which you can do by hand, short answer questions, and simulation exercises that you will complete using Joe Felsenstein’s PopG program. PopG is available for download here:

http://evolution.gs.washington.edu/popgen/popg.html

You are welcome to work in small groups on the homework as long as you write up your own solutions and specify who you worked with.

Text for Further Reading: Some homework problems will come from Graham Coop’s notes on population genetics. This text contains more detail about important concepts we will introduce in class. The notes are available for download here:

https://github.com/cooplab/popgen-notes/blob/master/popgen_notes.pdf

Grading: Grading will be based 50% on homework and 50% on class participation. To receive full credit for participation, students are expected to speak up at least once during every class.

Lecture Topics:

Below is a list of topics that I tentatively plan to cover during the 5 weeks of this course. Both the topics and the accompanying assignments are subject to change. If you are particularly excited about any of the topics below, or specific topics related to concepts that are on the syllabus, feel free to communicate that to me at any point so I can consider prioritizing that material.

January 7th: Intro to Genetic Variation as an Evolutionary Time Capsule

• An introduction to the structure of genetic variation and its ability to tell us about evolutionary history
• The life cycle of a genetic variant: mutation, drift, selection, fixation
• Allele frequencies, genotype frequencies, Hardy Weinberg Equilibrium
• Probabilistic assignment of individuals to populations

Homework assigned:

Problem Set #1

Homework due:

None

January 9th: Population Structure

• FST and the sharing of genetic variation within vs between populations
• The uses and limitations of the STRUCTURE topic model of population variation
• Using Principal Component Analysis to visualize genetic variability
• How population structure confounds the mapping of genotype-phenotype associations

Reading assigned:

R.C. Lewontin, “The apportionment of human genetic diversity,” Committee on Evolutionary Biology 1972.

Novembre, et al. “Genes mirror geography within Europe.” Nature 2008.

Homework due:

None

January 14th: Natural Selection

• Adaptation vs stabilizing selection
• Modeling a classical positive selective sweep
• Additive, recessive, and dominant modes of selection
• The effect of population size on selection efficiency

Homework assigned:

Problem Set #2

Homework due:

Problem Set #1

January 16th: Natural Selection II

• Different tests for natural selection probe different timescales (dN/dS, haplotype homozygosity, PBS, SDS)
• Hitchhiking and background selection
• Prediction and estimation of genetic load
• The difficulty of detecting polygenic adaptation and soft selective sweeps

Homework assigned:

None

Homework due:

Answers to questions on Lewontin and Novembre readings

January 21st: Inference of demography and its relationship to selection

• The relationship between population size and genetic diversity
• A brief introduction to coalescent theory
• Evidence for the action of selection on genetic load
• How population booms, population busts, and migration affect genetic diversity

Reading Assigned:

Li and Durbin. “Inference of population history from individual whole genome sequences.” Nature 2011

Homework due:

Problem Set #2

January 23rd: More on demography and effective population size

• A coalescent simulation activity

Reading assigned:

Henn, et al. “Estimating the mutation load in human genomes.” Nature Rev Genet 2015.

Murray, et al. “Natural selection shaped the rise and fall of passenger pigeon genomic diversity.” Science 2017

Homework due:

None

January 28th: Speciation and the evolution of sex

• Types of speciation
• Identifying speciation genes using classical genetics and FST scans
• Types of genetic conflict that drive speciation
• Evolution of sexual reproduction and sex chromosomes

Reading assigned:

Zhou and Bachtrog. “Sex-specific adaptation drives early sex chromosome evolution in Drosophila.” Science 2012.

Homework due:

Answers to questions on Li and Durbin reading

January 30th: Detection of past gene flow from ancient DNA

• Sequencing of the Neanderthal genome
• Using Patterson’s D statistic to detect introgression
• Genomic evidence for Neanderthal interbreeding

Reading assigned:

Hufford, et al. “The genomic signature of crop-wild introgression in maize.” PLoS Genetics 2013.

Homework due:

Answers to questions on Henn, et al. and Murray, et al. readings

February 4th: Local adaptation and adaptive introgression

• Distinguishing adaptive introgression from alternative selective and neutral scenarios
• The relationship between age and length of shared haplotypes
• The archaic origin of altitude adaptation in Tibetans

Reading assigned:

Fumagalli, et al. “Greenlandic Inuit show genetic signatures of diet and climate adaptation.” Science 2015.

Homework due:

Answers to questions on Zhou and Bachtrog reading

February 6th: Nothing in medical genetics makes sense except in light of evolution

• The “mystery of missing heritability”
• Polygenic scores and why they don’t easily “port” across populations
• Understanding why disease-causing alleles persist in the human gene pool
• Course wrap-up: how evolution informs our understanding of molecular biology

Homework due:

Answers to questions on Hufford, et al. reading and Fumagalli, et al. reading