Genetics - BIOL 2120 - Lecture Notes

I. Development of Evolutionary Theory
    A. Early theories
        1. Special creation - each species had separate origins
        2. Catastrophism
            a. Natural disasters that explained fossil record
            b. Extinction because of disasters
        3. Typological thinking = essentialism
            a. Small number of species
            b. Within species, number of types
            c. But each species is far different from all others
        4. Lamarck -
            a. Transformation of one species to another
            b. Inheritance of acquired characteristics
        5. Lyell
            a. Geologist
            b. Natural forces remain fairly constant over time
            c. Gradual change in earth
    B. Darwin's theory
        1. Evidence
            a. Fossils similar to existing species
            b. Observed results of massive earthquake
                (1) sea floor became dry land
            c. Galapagos Island finches (13)
                (1) differed in body size, beak morphology and function
                (2) occupied different ecological niches
        2. Malthus' essay on competition in populations for limited resources
        3. Why theory shook the world
            a. Earth more than 4000 - 6000 years old
            b. Rejection of catastrophism
            c. Rejection of goal-oriented changes
            d. Rejection of special creation
            e. Replacement of typological thinking with population thinking
            f. Abolition of anthropocentrism
II. Genetic Structure of Populations
    A. Overview
        1. Understanding phenotypic ratios in populations
        2. Only way get Mendelian ratios in population
            a. Must have each allele in frequency of 0.5
            b. If the allelic frequencies differ, will get different proportions
    B. Genotypic Frequencies
        1. at a specific locus (start with simple scenario with two alleles)
        2. how many are homozygous recessive?
        3. how many are heterozygous?
        4. how many are homozygous dominant?
        5. calculate by counting each group, divide number by total counted
        6. note that calculations made in lab were based on assumption
            a. Hardy-Weinberg Equilibrium had been reached
            b. can not make the assumption, then use in making H-W calculations
        7. must be able to distinguish heterozygotes
            a. may need to look at protein structure to identify different alleles
            b. although not seen at phenotypic level, detectable at molecular level
    C. Allelic Frequencies
        1. Assume random mating
            a. Frequency of alleles used to predict frequency of genotypes
        2. p = freq. of dominant allele in population
            a. (2*AA + Aa)/(2 * total)
            b. or (AA + ½Aa)/total
        3. q = frequency of recessive allele in population
            a. (2*aa + Aa)/(2 * total)
            b. or (aa + ½Aa)/total
        4. note that p + q = (2*AA + Aa + 2*aa + Aa)/(2 * total) = 1
        5. alleles, not genotypes, are passed to offspring
        6. fewer alleles than genotypes, so easier to define population parameters
        7. if three alleles: p + q + r = 1
            a. p = AA + ½(AB + AC)/total
            b. q = BB + ½(AB + BC)/total
            c. r = CC + ½(AC + BC)/total
        8. Blood types p = freq. A, q = freq. B, r = freq. O alleles
            a. A = p² + 2pr
            b. B = q² + 2qr
            c. AB = 2pq
            d. O = r²
        9. Sex-linked loci:
            a. p = AA + ½(Aa + AY)
            b. q = aa + ½(Aa + aY)
        10. Frequency of alleles can be used to predict frequency of genotypes
            a. Useful in predicting number of heterozygotes for deleterious alleles
III. The Hardy-Weinberg Law
     A. Assumptions
        1. large population
            a. no genetic drift
            b. genetic drift = chance deviations in allelic frequencies
            c. e.g. 10 people stranded on island; 5 blue eyed, 5 brown eyed
                (1) typhoon kills 5
                (2) all dead had brown eyes
                (3) drastic change in allelic frequencies
        2. random mating
            a. probability of two genotypes mating = the product of frequencies of each
            b. most species do not mate randomly, though for a given gene locus random
                mating may hold true
            c. e.g.. don' choose mate based on PTC tasting...
            d. some ways mating is not random
                (1) humans - IQ, education, socioeconomic status, height, skin color
                (2) harem, pecking order, appearance, strength
        3. no inbreeding
            a. founder effect (Amish polydactyly, Hopi albinism)
            b. bottleneck
            c. result is increase in homozygosity
        4. no mutation
            a. results in changing allelic frequencies
            b. but equilibrium when forward and back mutations balance out
        5. no migration
            a. serves to increase effective size of population
            b. adds different allelic frequencies
        6. no natural selection
            a. assumes both alleles are evolutionarily neutral
            b. no advantage of one over the other
        7. NONE of these assumptions holds true
            a. but allows us to have a null hypothesis
            b. test to see if gene locus is in equilibrium
            c. if not, determine which of these assumptions is false
    B. Predictions
        1. if H-W law satisfied, population is in genetic equilibrium (for that locus)
        2. expect frequencies of alleles to remain constant from generation to generation
        3. gene pool not evolving at this locus
        4. genotypic frequencies will be in proportions of p², 2pq and q² after one
            generation of random mating
        5. said to be in -W equilibrium until one of assumptions is not met
    C. Derivation
        1. if freq. of A is p, freq. of a is q
        2. assume all gametes thrown in pool (random mating)
        3. there are 4 combinations of gametes (show Punnett square)
        4. show that freq. of: AA = p², Aa = 2pq, aa = q²
    D. Extensions to Loci with More Than Two Alleles
        1. (p + q)²
        2. (p + q + r)²
        3. Ex. Blue mussel along Atlantic coast has three alleles for leucine
            aminopeptidase (LAP)
            a. LAP⁹⁸ p = 0.52
            b. LAP⁹⁶ q = 0.31
            c. LAP⁹⁴ r = 0.17
            d. Assume H-W; calculate expected frequencies
            e. p² = 0.27; 2pq = 0.32; q² = 0.10; 2qr = 0.10; 2 pr = 0.18; r² = 0.03
    E. Extensions to Sex-linked Alleles
        1. Females: p² (X^AX^A), 2pq (X^AX^a), q² (X^aX^a)
        2. Males: p (X^AY), q (X^aY)
        3. E.g.. color-blind allele in African Americans q = 0.039
            a. Calculate frequency in males and females
            b. Males: q = 0.039; females q² = 0.0015
            c. If sexes differ in allelic frequencies, seesaw back and forth until equilibrium
                is reached
    F. Testing for Hardy-Weinberg Proportions
        1. Count number of each of three classes (AA, Aa, aa)
        2. Using aa, calculate p and q, then expected p², 2pq, q²
        3. Chi square analysis on expected vs. observed
        4. Only one degree of freedom (once p is determined, all other values are set)
        5. E.g.. Red-backed vole transferrin (blood protein)
            a. 12 MM, 53 MJ, 12 JJ
            b. 1976, Northwest Territories of Canada
            c. Expected: 19.3, 38.5, 19.3
    G. Using the Hardy-Weinberg Law to Estimate Allelic Frequencies
        1. IMPT: can not then go back and test for H-W equil. (Circular reasoning)
        2. Recessive = q²
        3. Work way backwards to determine p and q
        4. estimate level of heterozygosity
IV. Genetic Variation in Space and Time
    A. Same species, different populations
    B. Same population, different times
V. Genetic Variation in Natural Populations
    A. Models of Genetic Variation
        1. Classical model
            a. One allele functions best
            b. Favored by natural selection
            c. Known as wild-type
            d. If new mutation is better, increases in frequency and takes over
            e. Consequences of model: limited genetic variability
            f. Does not fit with evidence gathered since proposal
            g. No longer viable model
        2. Balance model
            a. Natural selection that prevents any allele from reaching high frequency
            b. Maintenance of many alleles at a gene locus
            c. E.g.. Heterozygote superiority
        3. Neutral mutation model
            a. Recurrent mutation
            b. Random changes in allelic frequencies
            c. Explains large genetic variation
            d. Neither allele is strongly selected for
        4. Modes of natural selection
            a. Stabilizing selection
                (1) human birth weight
                (2) malaria, sickle cell trait
            b. Directional selection
                (1) used in agricultural breeding
                (2) also when environment constantly changing
            c. Disruptive selection
                (1) favors homozygotes
                (2) fragment population into subpopulations
                (3) may lead to reproductive isolation and distinct species
    B. Measuring Genetic Variation with Protein Electrophoresis
        1. Break open cells (e.g.. Blood cells)
        2. Run proteins on gel electrophoresis
            a. separate by size, shape, charge
            b. Use marker stain to highlight particular protein
        3. Recognize slight differences in charge, shape, size
        4. Can identify variants of given protein
        5. Determine proportion of polymorphic loci
            a. More than one allele
            b. # of genes with multiple alleles/ all genes observed
        6. Determine amount of heterozygosity
            a. Number of heterozygous loci of individual/total loci observed
    C. Measuring Genetic Variation with RFLPs and DNA Sequencing
        1. Restriction enzymes
            a. Cut specific sequence
            b. If mutation in DNA at that sequence, not cut
        2. Isolate DNA
        3. Cut with restriction enzymes
        4. Run on gel
        5. Use marker sequence to hybridize with gene of interest
        6. How many bands show up? Where are they located?
            a. Two short bands vs. one long band: RFLP
            b. If both two short and one long: heterozygote
        7. DNA sequencing shows more specific differences in genes
            a. Not just 4 or 6 base sequence
            b. Indicates numerous variations
VI. Changes in Genetic Structure of Populations
    A. Mutation
        1. Forward mutations (u)
            a. E.g.. u = 10^-4
            b. If 100,000 alleles in population
                (1) p = 1.0, all alleles are A; 10 will mutate to a
                (2) but if p = 0.1, 10,000 A alleles, only 1 will mutate
         2. Back mutations (usually slower rate) (v)
         3. Equilibrium reached when proportions of two alleles are such that forward
            and back mutations are equal
            a. This requires numerous generations
            b. But during this time, more mutations are introduced
        4. Populations rarely in mutational equilibrium
    B. Genetic Drift
        1. Chance changes in allelic frequencies
        2. Usually due to small populations or sudden reduction in population size
            a. Return to typhoon on island
            b. If population had been 1000, with 500 in each group
            c. Loss of 500 - less likely that all would be brown eyed
        3. Special cases of genetic drift
            a. Founder effect
                (1) population is large now, but at one time it was small
            b. Bottleneck
                (1) sudden reduction in population, then built back up
                (2) loss of genetic diversity
        4. Typically seen when population is in marginal habitat
        5. Habitat destruction fragments populations
            a. Prevents interbreeding
            b. Genetic drift in each isolated population
    C. Migration
        1. Few populations are completely isolated
            a. Islands
            b. Other geographical barriers
        2. Gene flow - movement of genes from one population to another
        3. Two factors affect influence of migration
            a. Difference in allelic frequencies between two populations
            b. Number of migrants
        4. Effectively increases the population size
            a. If one migrant in each direction every other generation
            b. Prevents gene fixation
    D. Natural Selection
        1. Survival of the fittest
        2. Key is that it is reproductive fitness
        3. Must contribute alleles to next generation
        4. Classic example: peppered moths
            a. Prior to 1848 all peppered moths 'typical'
            b. 1848 single dominant mutant 'carbonaria'
            c. 1900: more than 90% carbonaria in polluted areas
        5. Antagonistic pleiotropy
            a. Consider fitness to be number of eggs laid
            b. But may not be realistic: birds may not be able to feed all young, weaker
                and less likely to survive to reproduction
            c. Must always consider reproductive fitness
            d. Follow through to see if more grandchildren are produced
        6. Types of selection
            a. No selection - all adaptive values are equal
            b. One trait selected over other (recessive better, or dominant better)
                (1) note that when select against recessive trait, will rarely be eliminated in
                        population
                (2) protected polymorphism: hidden in heterozygote
                (3) if fitness of heterozygote is reduced, allele can eventually be eliminated
                        from population
            c. Heterozygote superiority (overdominance, heterosis)
                (1) sickle cell trait in Africa
            d. Heterozygote selected against - divergent
                (1) beak size in birds
    E. Nonrandom Mating
        1. Positive assortive mating
            a. Similar phenotypes mate preferentially
            b. E.g.. short guys and gals marry
        2. Negative assortive mating
            a. Opposites attract
            b. E.g.. Tall guys and short girls
        3. Does not affect allelic frequencies in population
            a. Influences genotypic frequencies
        4. Inbreeding - mating between close relatives
            a. Self-fertilization
        5. Outbreeding - form of negative assortive mating
VII. Summary of the Effects of Evolutionary Processes on the Genetic Structure of a     Population
    A. Changes in Allelic Frequency Within a Population
        1. Mutation
            a. such low rate, so frequently negligible
        2. Genetic Drift
            a. If population is small, significant factor
        3. Mutation, migration, selection
            a. May operate, but remain in balance
            b. So allelic frequencies remain constant
        4. Nonrandom mating affects genotypic, not allelic frequencies
    B. Genetic Divergence Among Populations
        1. Genetic drift increases divergence
        2. Migration decreases divergence
        3. Mutations in isolated small populations lead to greater differentiation between
            populations
        4. Natural election may favor different alleles in different populations
    C. Increases and Decreases in Genetic Variation Within Populations
        1. Migration and mutation introduce new alleles to gene pool
        2. Genetic drift removes alleles from gene pool
        3. Inbreeding leads to homozygosity
        4. Outbreeding increases variation
        5. Natural selection can increase or decrease variation
            a. Overdominance increases variation
             b. Allelic selection decreases variation
        6. All factors act in toto
VIII. Summary of the Effects of Evolutionary Processes on the Conservation of Genetic Resources
    A. Extinction
        1. Reduction in gene pool
        2. Loss of habitat
        3. Bottlenecks
        4. Zoo inbreeding
    B. Maintaining Biodiversity
        1. Maintenance of habitat
        2. Large populations
        3. Ability to migrate between populations
    C. Population viability analysis
        1. How large does population need to remain
        2. To keep from going extinct
        3. Over short period of time
IX. Molecular Genetic Techniques and Evolution
    A. DNA Sequence Variation
        1. Compare DNA sequences of species that diverged
        2. Determine rate of change of DNA (per nucleotide per year)
        3. Discover that not all DNA changes at same rate
        4. Nucleotide substitutions per site per year (x 10^-9)
            a. Functional genes
                (1) 5' flanking region: 2.36
                (2) leader: 1.74
                (3) coding sequence - synonymous: 4.65 (same a.a.)
                (4) coding sequence - nonsynonymous: 0.88
                (5) intron: 3.70
                (6) trailer: 1.88
                (7) 3' flanking region: 4.46
            b. Pseudogenes: 4.85
    B. DNA Length Polymorphism
        1. Short deletions and insertions within a gene
        2. Usually in introns and flanking regions: no effect on protein structure
        3. If insert or delete in exon, change in reading frame - select against
    C. Evolution of Multigene Families Through Gene Duplication
        1. May be due to transposition
        2. May be due to unequal crossover
        3. Opportunity for trial and error on developing better gene
        4. Globin gene family most notable
    D. Evolution in Mitochondrial DNA Sequences
        1. Animal mtDNA mutates at rate 5-10 x faster than nuclear DNA
            a. May be DNA polymerase more prone to errors, repair mechanism not as
                efficient
            b. Multiple mitochondria; selective pressure may not be as strong as in
                nuclear genes
        2. Plant mtDNA mutates slower than nuclear DNA
        3. Matriarchal lineages can be constructed 'mitochondrial Eve'
    E. Concerted Evolution
        1. Some genes maintain identical sequence even after duplicated
            a. mechanism not clearly understood
        2. Called concerted evolution or molecular drive
    F. Evolutionary Relationships Revealed by RNA and DNA Sequences
        1. Five kingdom system
        2. Now three kingdom system
            a. Archaea
            b. Bacteria
            c. Eukarya

For questions, comments and additional information, contact mfhicks@pstcc.edu
Last Updated: June 24 2001
Site map: Margaret F. Hicks Home - Biology 2120 - Notes - Population Genetics

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