Download Population Genetics

Prof. Dr. Fahd M. Nasr
Population Genetics course
Faculty of Sciences-Lebanese University
Population Genetics
M1 Biology
Course Syllabus
Code
BioA414
Title
Semester
Population S2 M1
Genetics
Credits
4
C
36 h
TS
LS
Total
36 h
Department of Life and Earth Sciences.
Course prerequisite
General Biochemistry and Genetics (S2), Molecular Genetics (S5), Molecular Biology (S6)
PS. This course focuses on the genetic and evolutionary aspects of populations; basic statistics
will be used. The course will not cover the sophisticated mathematical models that have
been devised to explain or predict the effect of several evolutionary forces acting in
combination to shape the genetic structure of modern populations. Hence, this course
should be considered as a substantial introduction to the broad field of Population
Genetics.
Aim
Population genetics is a subdiscipline of genetics that deals with genetic differences within
and between populations. This field examines phenomena such as adaptation, speciation,
and population structure. A major goal of this course is to make students familiar with
basic models of population genetics and to acquaint students with empirical tests of these
models. As much as any field of biology, population genetics has been divided into a
theoretical and an empirical branch. However, these two bodies of knowledge are
intimately related and this course will cover both in roughly equal amounts. We will
discuss the primary forces and processes involved in shaping genetic variation in natural
populations (mutation, drift, selection, migration, recombination, mating patterns,
population size and population subdivision), methods of measuring genetic variation in
nature, and experimental tests of important ideas in population genetics.
Outcome
Population genetics is the mathematical study of evolutionary processes. In this course you
will learn about the processes that determine the dynamics of alleles, genotypes, and
phenotypes over space and time. The laboratory in this course is a mixture of computer
simulation exercises and discussions of primary literature that will be assigned during the
semester. Your grade will be determined by your performance on problem sets and in
class discussion.
Perspective
Population genetics is a field of biology that studies the genetic composition of biological
populations and the changes in genetic composition that result from the operation of
various factors, including natural selection. Population geneticists pursue their goals by
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Prof. Dr. Fahd M. Nasr
Population Genetics course
Faculty of Sciences-Lebanese University
developing abstract mathematical models of gene frequency dynamics, trying to extract
conclusions from those models about the likely patterns of genetic variation in actual
populations, and testing the conclusions against empirical data.
Population genetics is intimately bound up with the study of evolution and natural selection,
and is often regarded as the theoretical cornerstone of modern Darwinism. This is because
natural selection is one of the most important factors that can affect a population's genetic
composition. Natural selection occurs when some variants in a population out-reproduce
other variants as a result of being better adapted to the environment, or ‘fitter’. Presuming
the fitness differences are at least partly due to genetic differences, this will cause the
population's genetic makeup to be altered over time. By studying formal models of gene
frequency change, population geneticists therefore hope to shed light on the evolutionary
process, and to permit the consequences of different evolutionary hypotheses to be
explored in a quantitatively precise way.
The original, modern synthesis view of population genetics assumes that mutations provide
ample raw material, and focuses only on the change in frequency of alleles within
populations. The main processes influencing allele frequencies are natural selection,
genetic drift, gene flow and recurrent mutation. Fisher and Wright had some fundamental
disagreements about the relative roles of selection and drift. The availability of molecular
data on all genetic differences led to the neutral theory of molecular evolution. In this
view, many mutations are deleterious and so never observed, and most of the remainder
are neutral, i.e. are not under selection. With the fate of each neutral mutation left to
chance (genetic drift), the direction of evolutionary change is driven by which mutations
occur, and so cannot be captured by models of change in the frequency of (existing)
alleles alone. The origin-fixation view of population genetics generalizes this approach
beyond strictly neutral mutations, and sees the rate at which a particular change happens
as the product of the mutation rate and the fixation probability.
The field of population genetics came into being in the 1920s and 1930s, thanks to the work
of R.A. Fisher, J.B.S. Haldane and Sewall Wright. Their achievement was to integrate the
principles of Mendelian genetics, which had been rediscovered at the turn of century, with
Darwinian natural selection. Though the compatibility of Darwinism with Mendelian
genetics is today taken for granted, in the early years of the twentieth century it was not.
Many of the early Mendelians did not accept Darwin's ‘gradualist’ account of evolution,
believing instead that novel adaptations must arise in a single mutational step; conversely,
many of the early Darwinians did not believe in Mendelian inheritance, often because of
the erroneous belief that it was incompatible with the process of evolutionary modification
as described by Darwin. By working out mathematically the consequences of selection
acting on a population obeying the Mendelian rules of inheritance, Fisher, Haldane and
Wright showed that Darwinism and Mendelism were not just compatible but excellent bed
fellows; this played a key part in the formation of the ‘neo-Darwinian synthesis’, and
explains why population genetics came to occupy so pivotal a role in evolutionary theory.
Course outline
I. Introductory remarks
I.1. Definition
I.2. Four disciplines in Genetics: Transmission Genetics, Molecular Genetics, Population
Genetics, and Quantitative Genetics
I.3. Mendelian populations and the gene pool
I.4. Genetic structure of a population: allelic and genotypic frequencies
I.5. The need for mathematical models and equations
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Prof. Dr. Fahd M. Nasr
Population Genetics course
Faculty of Sciences-Lebanese University
I.5.1. Hardy-Weinberg law
I.5.2. Two-allele, multiple-allele, and X-linked loci
I.5.3. Genetic equilibrium
II. Applications to HW model
II.1. Genetic variation in space and time
II.2. Derivation of the Hardy-Weinberg law
II.2.1. Assumptions and deviations
II.2.2. Algebraic proof of genetic equilibrium
II.2.3. Clines or clinal variation: spatial and temporal
II.2.4. How to solve population genetics problems?
II.3. Calculations of allele frequencies for recessive traits
II.3.1. Genetic diversity of albinism
II.3.2. Other autosomal recessive traits: cystic fibrosis, phenylketonuria, etc.
II.4. Autosomal dominant traits: Neurofibromatosis 1, Huntington's disease (HD),
Marfan's syndrome, etc.
II.5. Sex-linked traits
III. DNA markers for genetic mapping and analysis of DNA polymorphisms
III.1. DNA markers: RFLPs, SSLPs, and SNPs
III.2. DNA molecular testing: scoring for an RFLP e.g. the -globin gene
III.3. SSLPs: VNTRs (Minisatellites) and STRs (Microsatellites)
III.4. SNPs: definition, consequences and importance in mapping
III.4.1. Various methods for SNPs typing: allele-specific oligonucleotide (ASO) and
DNA chip technology
III.4.2. ASO: solution hybridization techniques, Oligonucleotide ligation assay (OLA),
and amplification refractory mutation system (ARMS test)
III.5. Nuclear genome organization
III.5.1. Variations in gene density in eukaryotic genomes
III.5.2. The composition of the human genome
III.5.3. Classes of interspersed repeats in the human genome
III.5.4. Genome anatomy of the yeast and other model systems
III.5.5. Families of genes: multigene families and gene-superfamilies
III.6. Acquisition of new genes
III.6.1. Two different ways: acquiring genes from other species or duplicating some or
all of the existing genes in the genome
III.6.2. Outcome of gene duplication: three scenarios
III.6.3. Duplications and synteny
III.6.4. Evolution of the globin gene superfamily of human
III.6.5. Developmental homology
III.7. Processes resulting in gene duplication
III.7.1. Unequal crossing-over and replication slippage
III.7.2. Molecular mechanisms for creating new gene structures
III.7.3. Gene evolution: orthology and paralogy
III.7.4. Pseudogenes: conventional and processed
III.8. Mobile genetic elements (MGEs)
III.8.1. Discovery and general features of transposable elements
III.8.2. RNA transposons: LTR and Non-LTR retroelements
III.8.3. DNA transposons: types and properties
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Prof. Dr. Fahd M. Nasr
Population Genetics course
Faculty of Sciences-Lebanese University
III.8.4. Transposable elements in the human and yeast genomes
III.8.5. The Ac-Ds System in Maize
III.8.6. Drosophila transposons: the P element
IV. Genetic variation in natural populations
IV.1. Measuring genetic variation
IV.2. Genetic variation: DNA and protein levels: phenotype [rosy] in Drosophila
IV.3. Amount of genetic variation
IV.4. Two parameters for genetic variation: proportion of polymorphic loci and
Heterozygosity
IV.5. What maintains genetic variation within populations?
IV.5.1. The classical model
IV.5.2. The neutral mutation model
V. Forces that change gene frequencies
V.1. Four evolutionary processes: random mating, mutation, genetic drift, migration, and
natural selection
V.2. Mutation: Heritable changes within DNA
V.2.1. Raw material for evolution
V.2.2. Mutation rate varies between loci and among species
V.2.3. Rates of mutations: forward and reverse
V.2.3.a. Equilibrium frequencies
V.2.3.b. Irreversible vs reversible mutations
V.2.4. Effective population size
V.2.5. Probability of fixation of a new neutral mutation
V.2.6. Fixation of a new favorable mutation
V.3. Genetic drift: sampling errors
V.3.1. Fisher-Wright model of genetic drift
V.3.2. Sampling occurs naturally
V.3.3. The concept of a genetic bottleneck
V.3.3.a. Genetic Bottleneck: historical cases
V.3.3.b. Bottleneck and founder effects
V.3.4. Neutral theory of molecular evolution
V.3.5. Balance between mutation and genetic drift
V.3.6. Assumptions of the infinite alleles model
V.3.7. Relationship between the neutral parameter  = 4 Ne  and the expected
heterozygosity
V.4. Migration of gene flow
V.4.1. Theoretical model
V.4.2. Extensive gene flow occurs among natural populations
V.4.3. Types of barriers to gene flow
V.5. Natural selection and the process of adaptation
V.5.1. Adaptation to environment
V.5.2. Examples of natural selection
V.5.3. Three forms of natural selection
V.5.4. Darwinian fitness (W) and selection coefficient (S)
V.5.5. Effects of selection
V.5.5.a. Types and formulas
V.5.5.b. Heterozygote superiority: heterosis, hybrid vigor, or overdominance
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Prof. Dr. Fahd M. Nasr
Population Genetics course
Faculty of Sciences-Lebanese University
V.5.6. Balance between mutation and selection
V.6. Random mating
V.6.1. Assortative mating: positive and negative
V.6.1. Effects of inbreeding
VI. Populations and Species
VI.1. How do populations evolve?
VI.2. Stability and change
VI.3. Speciation and Extinction
VI.4. Two models of speciation: cladogenesis and anagenesis
VI.4.1. Microevolution and macroevolution
VI.4.2. Distinguishing Homology from Analogy
VI.5. Modes of speciation
VI.5.1. Species concept
VI.5.1.a. The Typological species concept
VI.5.1.b. The phenetic or numerical taxonomy species concept
VI.5.1.c. The biological species concept
VI.5.1.d. The evolutionary/phylogenetic "species" concept
VI.5.1.e. Is there a perfect species concept?
VI.5.2. What is a species?
VI.5.3. How do species arise?
VI.5.4. Allopatric, peripatric, parapatric, and sympatric speciation models
VI.5.5. What is the evidence for parapatric speciation? (ring species)
VI.6. Many intrinsic reproductive isolating mechanisms drive speciation
VI.6.1. Reproductive barriers keep species separate
VI.6.2. Genetic basis of reproductive isolation
VI.6.2.a. What causes post-zygotic isolation?
VI.6.2.b. Dobzhansky-Muller incompatibility
VI.6.2.c. Epistatic interactions
VI.6.3. Speciation genes
VI.6.3.a. What types of genes are involved in speciation?
VI.6.3.b. The Xmrk-2, OdsH, Hmr, and desat-2 loci
VI.7. Speciation occurs at widely differing rates
VI.8. Sexual selection
VI.9. Mass Extinctions are a fact of life
VI.10. Conservation of biodiversity
VI.10.1. Distinguishing features of living organisms
VI.10.2. Why study biodiversity?
VI.10.3. Components of biodiversity
VI.10.4. Regions and ecosystems vary in biodiversity
VI.10.5. What is the “biodiversity crisis”?
VI.10.6. What are the biggest threats to biodiversity?
VI.11. Molecular phylogenetics
VII. Quantitative Genetics
VII.1. Quantitative Traits
VII.1.1. Types of quantitative trait
VII.1.2. Quantitative genetics basic assumptions
VII.2. Autopolyploids and allopolyploids
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Prof. Dr. Fahd M. Nasr
Population Genetics course
Faculty of Sciences-Lebanese University
VII.3. Genetic effects on quantitative traits
VII.4. Separating genetics from environment
VII.4.1. Johannsen’s experiments
VII.4.2. Work out the basis of artificial selection
VII.5. Mathematical basis of Quantitative Genetics
VII.5.1. Heritability
VII.5.2. Additive vs. dominance genetic variance
VII.5.3. Narrow sense heritability
VII.5.4. Heritability in a selection experiment
VII.5.5. Realized heritability
VIII. Evolution at multiple loci
VIII.1. Evolution at two loci
VIII.1.1. Pair of loci located on same chromosome
VIII.1.2. Allele and chromosome frequencies
VIII.1.3. Linkage equilibrium and linkage disequilibrium
VIII.1.4. Conditions for linkage equilibrium
VIII.1.5. Coefficient of linkage disequilibrium
VIII.2. What creates linkage disequilibrium in populations?
VIII.2.1. Selection on multilocus genotypes
VIII.2.2. Genetic drift
VIII.2.3. Population mixing
VIII.3. What eliminates linkage disequilibrium from population?
VIII.4. Genetic recombination: Empirical example
VIII.5. Practical reasons to measure linkage disequilibrium
VIII.5.1. Reconstructing history of the CCR5-D32 locus
VIII.5.2. Using LD to detect strong positive selection
VIII.5.3. G6PD and malaria
VIII.6. Adaptive significance of sex
VIII.6.1. Maynard Smith’s assumptions
VIII.6.2. Dunbrack et al. (1995) experiment
VIII.6.3. Sex in populations means genetic recombination
VIII.6.4. Why is sex beneficial?
VIII.6.5. Genetic drift plus mutation: Muller’s ratchet
VIII.6.6. Anderson and Hughes (1996) test of Muller’s ratchet in bacteria
VIII.6.7. Selection favors sex in changing environments
VIII.6.8. Do parasites favor sex in hosts?
References
Hartl, D. and Clark, A. Principles of Population Genetics. 2006, Fourth Edition Sinauer
Associates: Sunderland.
Hedrick, P.W. Genetics of Populations, Third Edition. 2005, Jones and Bartlett Publishers,
Sudbury, MA.
Kartavtsev, Y. Molecular Evolution and Population Genetics for Marine Biologists. 2015,
CRC Press.
Peng, B., Kimmel, M. and Amos, C.I. Forward-Time Population Genetics Simulations:
Methods, Implementation, and Applications. 2012, John Wiley & Sons.
Templeton, A.R. Population Genetics and Microevolutionary Theory. 2006, John Wiley and
Sons.
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