Populations, Genes, and Allele Frequencies

1.  -Definitions:
              Population:  a local group belonging to a single species, within which mating is
                                      actually or potentially occurring.
              Gene Pool:  the set of genetic information carried by all interbreeding
                                      members of the population is called the gene pool.
              Allele Frequency:  measurement of the proportion of individuals in a population
                                      carrying a particular allele.

2  Conditions were you could directly measure the allelic frequencies in a population.
                -EXAMPLE:  MN blood group
                                   Population of 100 individuals:
                                      36 are MM, 48 are MN, 16 are NN
                                      36 MM = 72 M alleles + 48 M alleles (from MN) = 120 M alleles
                                      Frequency of M allele in the population = 0.6 (120/200 = 0.6)
                -When the condition described above is not present, the measure allelic
                  frequencies is accomplished with the Hardy-Weinberg Law.

3.  In the Hardy-Weinberg Law, the following conditions are presumed to exist:
            1. The population is infinitely large, or large enough that sampling error is
                 negligible.
            2.  Mating within the population occurs at random.
            3.  There is no selective advantage for any genotype; all genotypes are equally
                  viable & fertile.
            4.  There  is an absence of factors such as mutation, migration, and random
                  genetic drift.

4.  In the Hardy-Weinberg law the dominant allele is represented by p and the recessive
     allele is represented by q.

5.  p+q=1    Because the sum of p and q represents 100% of the alleles from that gene
     in the population.

6.  Diagram of the allelic frequencies of a cross using a Punnett square showing how
     the equation for the distribution of genotypes in the next generation can be
     expressed.

     Allele frequencies determine genotype frequencies.

Example:  A population with 70% of the alleles for a given gene are A, and 30% are a.  For this population, p=0.7, q = 0.3, and p+q = 0.7+0.3 = 1  The distribution and frequency of genotypes produced by random mating are as follows:

7.   A population in which the frequency of a given allele remains constant from
      generation to generation is in a state of genetic equilibrium for that allele.
      Since the frequencies of the allele remain constant, the conditions presumed for the
      Hardy-Weinberg law hold true in this population.

      -Three important points are relevant to the preceding example:
                 1. While hypothetical alleles are at equilibrium, not all alleles in a population
                      may be in equilibrium.  This is particularly true when the assumptions made
                      in the Hardy-Weinberg law do not hold .
                2. The example above demonstrates why dominant traits do not tend to
                     increase in frequency as new generations are produced.
                3. The example illustrates that genetic equilibrium maintains a state of gene
                     variety in a population.  Allele frequencies remain unchanged during
                     equilibrium - a factor important to the evolutionary process.

8.  -Determining the frequencies for X-linked genes in human males.
       The phenotype of both dominant and recessive alleles is expressed.
       The frequency of an X-linked allele of a gene is the same as its phenotypic
        frequency.
        Example:
            In Western Europe a form of X-linked color blindness occurs in 8% of the males
            (q = 0.08).  The expected frequency in females of this population is q² or
            0.0064.
                            800 out of 10,000 males would be expected to be colorblind
                            64 of 10,000 females would be expected to be colorblind

9.  -Equation used to determine the frequency of 3 multiple alleles in an equilibrium
       population:        (p + q + r)²
     -Equation used to determine the genotype frequencies of three multiple alleles
        in an equilibrium population.   p² + 2pq + 2pr + q² + 2qr + r² = 1
     -EXAMPLE:  ABO blood groups
       An equilibrium population the frequency are: A(p)=0.38, B(q)=0.11, O(r)=0.5
       What are the phenotypic and genotypic frequencies for A, B, and O type blood?

 10. A practical application of the Hardy-Weinberg law is calculation of heterozygote
       frequency in a population.
         -  Frequency of a deleterious recessive phenotype can be determined by counting
            individuals in a sample population.
         -  Albinism:  autosomal recessive trait with incidence of about 1/10,000
                              q² =  0.0001
                              q = 0.01 or 1/100 and thus p= 0.99.
                              The frequency of heterozygous is 2pq = 0.02 or 2% (1/50)

          -Important to note how fast  heterozygotes increase in a population as values of p
           and q move away from zero.  If a recessive trait is rare, the majority of those with
           the trait are heterozygotes.

11. Factors that alter allele frequencies:

       - In nature populations rarely reach equilibrium.  Hardy-Weinberg relationship
         provides an opportunity to study the forces that introduce and maintain genetic
         diversity.
 

Mutation:  sorce of new alleles
Gene pool in a population is reshuffled by assortment and recombination, but does not lead to new alleles.

12. -New alleles are created by mutation.  Mutation is a negligible force in
        changing allele frequencies.
      -Most mutations are recessive and thus difficult to  measure in a diploid
       organism. Dominant mutations can be measured directly if the following
       criteria are met.
             1. The trait must produce a distinctive phenotype that can be
                 distinguished from similar traits produced by recessive allele.
             2. The trait must be fully expressed or completely penetrant so that
                  mutant individuals can be identified.
             3. An identical phenotype must never be produced by nongenetic
                  agents such a drugs or chemicals.

13. - Mutation is a major force in creating new genetic variability, but by
         itself has an insignificant role in changing allele frequencies.
       -Mutation rates are expressed as the number of new mutant genes per
        given number of gametes.
      -2 individuals out of a population of 100,000, are observed with a
        new dominant mutation.  Zygotes that produced these offspring each
        carry two copies of the gene,  have  surveyed 200,000 copies of
        the gene (200,000 gametes).  Assume the affected individuals are
        heterozygous, have uncovered 2 mutant alleles out of 200,000.
        Mutation rate (m) would be 2/200,000 or 1/100,000 = 1X10^-5.
        Hardy-Weinberg Law to estimate the change in frequency
        for the next generation.  If the normal individuals are aa, the frequency
        of "a" (q_o) is 1.0 and the frequency of the mutation "A" is p_o.  If the rate
        of mutation from aÞA is m, then in the next generation:

        New frequency for a, lowered by the rate of mutation is expressed:

      - The rate of mutation is constant form generation to generation.
      - The rate of change in the frequency of the mutant allele is initially high,
         but  declines to zero as equilibrium is approached.
      - Mutation is important in initial changes in an allele frequency, but the
         final frequency is determined by selection.
      - Example:  It would take 70,000 generations to reduce the frequency of
        A to 0.5. Mutation is a major force in generating genetic variability, but
        by itself has an insignificant role in changing allele frequencies.

Migration:  movement between populations

A species becomes divided into subpopulations that may be geographically isolated.  Differences in mutation rate and selective pressures can establish different alleles frequencies in  subpopulations.  Migration occurs when individuals move between these populations.

13. Equation for change in frequency of an allele in one generation caused
       by migration is:   Dp = m (p_m - p)
                                                p = frequency of A in the existing population
                                                p_m = frequency of A in immigrant population
                                                Dp = change in one generation
        m = coefficient of migration = proportion of migrant genes entering the
                population per generation.
     -Change in allelic frequency in one generation for a population where
       p=0.4, pm= 0.6, and 10% of the parents giving rise to the next
       generation are immigrants:
                     If p=0.4, pm=0.6, 10% of parents are immigrants then
                     Dp=m(p_m-p)
                          =0.1(0.6-0.4)
                          =0.02

        -In the next generation, the allele frequency of A (p₁) will increase as
         follows:
                         p₁ = p + Dp
                              =0.4 + 0.2
                              = 0.42

If m is large and/or if p is larger or smaller than p_m, then a large change in frequency of S will occur in a single generation.  An equilibrium will be obtained when p=p_m.

Selection: Mutation and migration introduce new alleles into the population
14. - Natural selection is the principal force shifting allele frequencies within
         large populations
       - One of the most important factors in evolutionary change.
       - When a genotype/phenotype confers an advantage to organisms in
          competition compared to another alternative genotype/phenotype
          combination, selection occurs.

        - Fitness: measure of an organism's ability to survive and leave spring.
                          Total Reproductive Potential.
        - Selection coefficient (s): mathematically calculated difference
                           between the fitness of a given genotype.
        - Equation for determining the effect of selection on successive
           generations in a population: q_n = q_o/1+nq_o
                            n = number of generations elapsing since p_o and q_o
           In the beginning reduction of a lethal allele will be high.  Eventually
           selection becomes negligible.  Selection operates on phenotypes,
           and thus the heterozygotes are not selected against.  Subsequent
           reduction in allele frequency occurs slowly and depends on  removal
           of heterozygotes.  Therefor it is difficult to remove  recessive alleles
           from a population.

        -Eugenics?
         Selective breeding of humans to improve the species.  Suggested that
          individuals suffering form serious genetic disorders should be
          prohibited from reproducing to reduce the frequency of  disorders in
          future generations.  Suppose that  a detrimental trait is present in the
          population at a frequency of 1 in 40,000, and that affected individuals
          do not reproduce.  In 100 generation (about 2500 years), what would
          be the frequency of the condition?  What are your assumptions about
          the eugenic measures effective in this case?
                      q_n = 0.000025/1+(100 X 0.000025)
                           = 0.000024

                      q_o = 1/40,000
                           =0.000025

                      assume: s=1
                                     n=100
                                    q = 0.000025

                      1/0.000024 = 41,666
                      so 1/41,666 = frequency of the condition in 100 generations

15.  Three  types of selection:
        Selection acts on phenotype/genotype combination of polygenic or
        quantitative traits.  Selection for such traits can be:
             1. Directional:  a selective force that changes the frequency of an
                                       allele in a given direction, either toward fixation or
                                       toward elimination.  Often shifts toward extreme
                                       phenotypes occur.  Tends to produce genetic
                                       uniformity.
             2. Stabilizing selection:  preferential reproduction of those
                                       individuals having genotypes close to the mean for
                                       the population.  A selective elimination of genotypes
                                       at both extremes.  Stabilizing selection represents a
                                       population  that has adapted to its environment.
                                       Example:  Human Birth Weights
             3. Disruptive selection:  simultaneous selection for phenotypic
                                       extremes in a  population, usually resulting in the
                                       production of two discontinuous trains.
                                       Occurs in population in heterogeneous environments.

16.  - Genetic Drift:  Random variation in gene frequency form generation to
          generation.  Often observed in small populations.
        - Random fluctuations in allele frequencies occur strictly on the basis of
          chance deviations.  Degree of fluctuation will increase as population
          size decreases.
         - Genetic drift may lead to fixation of an allele.

        - How small populations created in nature:
                  1.  Large population split by natural or man made event.
                  2.  Natural disasters that limit the number of individuals left to
                       reproduce
                  3.  Emigration (founder effect) to a new environment
 
Inbreeding

17. -Assortative mating:
               Nonrandom mating between males & females of a species.
               Selecting of mates with the same genotype is positive
               Selection of mates with opposite genotypes is negative

        - Inbreeding?:
               Mating between closely related organisms.
               Results in increased homozygosity and reduced heterozygosity.
               Self-fertilization is the most extreme example.

        -Consanguineous matings:
                Related by a common ancestor with the previous generation.
                Coefficient of inbreeding (F): Probability that two alleles of a given
                                   gene in an individual are derived from a common allele
                                   in an ancestor.
                                  F= 0 is no allele present are derived from a common
                                        ancestor.
                                  F=1 all genotypes are homozygous and derived from a
                                        common ancestor.

        - Genetic Burden:  number of heterozygous recessive allele that are
                                  lethal or deleterious in the homozygotes.

        -Inbreeding Depression:  
                    -An expression of reduced fitness is a population caused by
                          inbreeding.
                    -Increases homozygousity in individuals
                    -Reduces genetic variability.
                    -Both favorable and unfavorable alleles will become more
                          homozygous.
                    -Ability of the population to adapt to changing conditions will
                          decrease.

Heterosis
18.   Heterosis:
             -Hybrid Vigor:  Superiority of a heterozygote over either homozygote
                                       for a given trait.
             -Extends only to the first generation
             1. Dominance Hypothesis - reversal of inbreeding depression.
                                                Masking of deleterious recessive alleles.
             2. Overdominance - heterozygous generally superior to the
                                                homozygote.  Biochemical diversity.