Supplemental Lecture (97/02/21 update) by Stephen T. Abedon (abedon.1@osu.edu)

  1. Chapter title: Genetics
    1. A list of vocabulary words is found toward the end of this document
    2. Genetics is the study of heredity, which is the movement of non-cultural (i.e., non-acquired), biologically coded information from parent to child. This information is encoded, predominantly, on the molecule known as DNA (or as RNA in some viruses). There it takes the form of long sequences of nucleotide bases. In fact, the most fundamental aspect of life is the existence of this information and its passage to offspring.
    3. To a large extent DNA information is organized into discrete units called genes, and genes, in turn, encode (template) the production of linear, polymeric macromolecules such as RNA and proteins. Genes display consistent locations on chromosomes (called loci). However, variation exists within populations of individuals between genes found at the same loci. Some of this variation also exists within individuals and often it is readily observable. Consequently, it is possible to keep track of the variation found at many loci as chromosomees are passed through generations.
    4. Heredity, and thus genetics, encompasses all of these aspects of genes, ranging from how genes make gene products (molecular genetics) to how genes behave among populations of individuals (population genetics). In this lecture we will consider a number of core concepts of genetics, especially as they relate (mostly non-molecularly) to the movement of genes from parent to offspring, and in the absence of evolution.
  2. Hereditary [genetic] material
    1. A substance capable of templating its own replication.
    2. Without exception, biological hereditary material consists of either the nucleic acid DNA, or, less frequently, the nucleic acid RNA.
    3. The concepts of hereditary material and that of genotype are intimately related.
  3. Genome
    1. A complete set of hereditary material possessed by an organism within its chromosome(s).
    2. Strictly, a diploid or polyploid organism possesses more than one genome while a haploid organisms possesses only one.
  4. Gene
    1. Discrete, linear units of information encoded on chromosomes.
    2. See one gene, one polypeptide.
  5. One gene, one polypeptide
    1. Classically, this was stated as one gene, one protein, but today we know that proteins are composed of polypeptides.
    2. The idea is that a gene encodes the information necessary to allow the synthesis of a polypeptide.
    3. All necessary information:
      1. Even more generally, but still basically correct, a gene is an entity that codes for the synthesis of an RNA molecule).
      2. This all can get additionally complicated since in addition to the information needed to synthesize a polypeptide (and/or RNAs), genes often contain all sorts of information as to when and where a polypeptides may be made.
      3. All of these ideas are embodied in the word gene.
  6. Locus [pl. loci]
    1. The specific location on a chromosomes where a gene resides.
    2. Generally these locations are invariant and exceptions are considered to be interesting.
  7. Allele
    1. Same location, different sequence:
      1. Two genes of similar though not quite identical sequence, located at the exact same loci on two different chromosomes are said to be allelic.
      2. Note that the sequence difference between alleles need not be dramatic and, in fact, tends not to be dramatic. Instead it usually is limited to one, or at most a few, nucleotide differences.
    2. Within a given species, a given locus often has more than one allele associated with it (and the associated gene is said to be polymorphic).
    3. Very often different alleles can be distinguished in terms of differences in their physical impact on the organism. That is, they may be associated with (often readily measurable) phenotypic differences.
  8. Genotype
    1. All of the alleles carried by an individual. Also, the substance and potential of the hereditary material possessed by an individual.
    2. Thus, two individuals usually differ "genetically" and this is technically expressed as each individual possessing a different genotype.
    3. In classical terms, the genotype was inferable but otherwise unknowable. However, today, on a molecular level, genotype and sequence are equivalent.
  9. Phenotype [trait]
    1. The physical characteristics of an individual; the realized genotype.
    2. Genotype tends to influence (significantly) phenotype via numerous polypeptide (etc.) intermediaries.
    3. However, a given genotype does not guarantee a given phenotype. This is because the environment an organism exists in can influence its phenotype.
    4. Particularly, phenotype is a composite expression of genotype, environment, and some degree of interaction (e.g., feedback) between genotype and environment.
  10. Homozygote [homozygotic, homozygous]
    1. In a diploid individual, a homozygote is one that contains two identical alleles at a single (or more) specified loci.
    2. Recall that embodied in the concept of diploidy is the idea that an individual has two of each type of chromosome. This all but guarantees that the same individual will also have two copies of each gene and thus two alleles at each loci (i.e., one on each chromosome type). In a homozygote, these two alleles are identical.
  11. Heterozygote [heterozygotic, heterozygous]
    1. Non-identical alleles:
      1. In a diploid individual, a homozygote is one that contains two non-identical alleles at a single (or more) specified loci.
      2. Note that two alleles located at a given loci and carried by a heterozygote do not influence each other chemically (at least not usually).
    2. Meiotic variation:
      1. The alleles passed to progeny by a heterozygote tend to not differ from those passed from a homozygote except in terms of numbers of types.
      2. Note that upon meiosis one would expect a heterozygote to give rise to two haploid daughter cells each carrying one allele, and a second two haploid daughter cells each carrying the second allele. In other words, one-half and one-half.
  12. Recessive
    1. In a heterozygote, an allele which has no positive (or negative) influence on phenotype, but whose adjacent allele does, is called recessive.
    2. Lack of function:
      1. Recessiveness often results from lack of function.
      2. In other words, with one gene, one polypeptide, one might suppose that a recessive allele is genetically incapable of producing an associated non-defective polypeptide.
    3. See dominant allele.
  13. Dominant
    1. The flip side of a recessive allele. A dominant allele is, minimally, one which is capable of exerting an influence on phenotype.
    2. Heterozygote = homozygous dominant:
      1. Classically, a heterozygote consisting of a dominant and a recessive allele have the same phenotype as a homozygote carrying two copies of the same dominant allele.
      2. In addition, both the heterozygote and homozygote (carrying one or two copies of the dominant allele, respectively) will display a phenotype which differs from that expressed by a homozygote carrying two copies of the recessive allele.
  14. Bacteria are haploid
    1. Automatic homozygosity:
      1. Bacteria generally have only a single chromosome per cell. Consequently, they tend to have only a single copy of any given gene. Any mutation in one of those genes will therefore be expressed (to the extent, at least, that expression may occur within the context of protein regulation).
      2. This haploid nature of bacteria (and any other organisms existing in a haploid state) contrasts with the diploid nature of many of the organisms you are familiar with such as most animals, etc. In other words, bacterial alleles tend to be neither dominant nor recessive, or at least rarely tested as such in the wild.
  15. Wild type
    1. A description of an allele which naturally occurs in wild populations, often at a relatively large frequency, thus taken to represent how the allele normally operates in a wild individual.
    2. Non-defective allele:
      1. Often wild type is contrasted with alleles found at the same loci which contain one or more defects.
      2. Particularly, wild type alleles are often dominant (though not always since there are numerous cases of defective alleles which are capable of dominating the phenotype associated with the wild type allele).
      3. The concept of wild type can be confusing when more than one allele is substantially and similarly frequent at a given loci within a wild population.

  16. Abbreviating alleles

    1. Recessive and DOMINANT:
      1. Alleles are often represented as italicized abbreviations.
      2. By convention, a recessive allele is written in lower case (i.e., a as opposed to A), and a dominant allele is written in upper case (i.e., A).
      3. Note that conventions become more complicated in situations in which there are more than two alleles at a given loci.
    2. A diploid individual may therefore be designated AA, Aa, or aa depending on the alleles present at locus A (homozygous dominant, heterozygous, homozygous recessive, respectively).
  17. Crossing [cross, test cross]
    1. A mating (i.e., sexual reproduction) between two individuals.
    2. Crossing and examining progeny is a way (often the only not biochemical one) of teasing out genotype information from phenotype information.
    3. Note that a cross between an AA individual and an aa individual would be represented as AA x aa.
  18. Selfing [self]
    1. A mating (i.e., sexual reproduction in which maximal inbreeding has been achieved) in which a single individual serves as both parents.
    2. This is common among some types of plants.
  19. Backcross
    1. A mating that occurs between generations, particularly, between a parent and an F1 offspring. The term backcross also refers to an individual that is the product of such a mating.
  20. Progeny
    1. Offspring.
  21. F1 [F2, etc.] generation
    1. The individuals (or individual) mating in the first round of a genetics experiment is called the parental generation.
    2. Offspring:
      1. Subsequent generations are numbered as subscripts of F (for filial).
      2. Thus, the first generation of progeny are called the F1 generation, the progeny of matings among the F1 generation are called the F2 generation, etc.
  22. Mendelian ratio
    1. Start with a cross between two homozygotes, each containing different alleles at the same loci. In the F1 generation, this cross will be represented by heterozygotes each containing one allele from one parent and another allele from the other parent. That is, there is only one type of individual which results, a heterozygote.
    2. Three F2 genotypes:
      1. Mating within the F1 generation, however, leads to three different types of individuals in the F2 generation.
      2. Two are homozygous for each allele and two are the same as that represented in the F1 generation.
    3. Dominant-recessive pair:
      1. If one of the alleles is recessive and the other dominant, then:
        1. the parental generation will display two distinct phenotypes
        2. the F1 generation will display only a single phenotypes (i.e., that associated with the dominant allele)
        3. the F2 generation will display two distinct phenotypes.
      2. One of the F2 generation phenotypes will be displayed by the lone recessive homozygote, while the dominant phenotype will be displayed by all the others.
    4. Using letter stand-ins for alleles such that A is the dominant allele and a is the recessive allele, then the parental generation consists of AA and aa, the F1 generation consists of Aa only, and the F2 generation consists of one AA, one aa, and two Aa.
    5. Three-to-one ratios:
      1. If any individual carrying at least one A expresses the dominant phenotype, then the ratio of F2 generation phenotypes is expected to be 3:1 in favor of the dominant phenotype.
      2. This is the Mendelian ratio.
      3. Remember that all of this occurs as a consequence of the sexual cycle (i.e., haploid begetting diploid begetting haploid, etc.) and random mating between the various participants (in this case, within generations rather than random mating between generation).
    6. In short, a Mendelian ratio is achieved in the F2 when two homozygotes are crossed, one homozygous for a dominant allele and the other homozygous for a recessive allele. The ratio consists of two phenotypes being present 3 to 1, dominant to recessive, for reasons considered in detail above.
  23. Punnett square
    1. A relatively easy way of keeping track of ratios of alleles expected in progeny.
    2. Example:
      1. Below the frequency (f) of an allele among the males in a mating is described in shorthand: f(A,male) or f(a,male) which repectively describes the frequency of male gameters carrying the dominant allele and the frequency of male gametes carrying the recessive allele.
      2. Multiplying the male frequency by the frequency of an allele among the females {f(A,female) and f(a,female), below} gives the frequency of that allelic combination among the next generation, which in most cases is the same for both male and female.
                 f(A,male)   f(a,male)  
                   = w          = x     
              --------------------------
              |           |            |
              |           |            |
f(A,female)   |   f(AA)   |   f(aA)    |
   = y        |   = w*y   |   = x*y    |
              |           |            |
              |           |            |
              --------------------------
              |           |            |
              |           |            |
f(a,female)   |   f(Aa)   |   f(aa)    |
   = z        |   = w*z   |   = x*z    |
              |           |            |
              |           |            |
              --------------------------
      1. Note that Aa and aA are equivalent so the frequency of f(Aa) or f(aA) is x*y + w*z.
    1. Example: Mendellian ratio:
      1. A specific example below is the special case where all initial frequencies are 0.5 (i.e., f(Aa) = 1.0). This parental generation is equivalent to the F1 generation generation discussed under Mendelian ratio:
                 f(A,male)   f(a,male)  
                   = 0.5       = 0.5    
              --------------------------
              |           |            |
              |           |            |
f(A,female)   |   f(AA)   |   f(aA)    |
   = 0.5      |   = 0.25  |   = 0.25   |
              |           |            |
              |           |            |
              --------------------------
              |           |            |
              |           |            |
f(a,female)   |   f(Aa)   |   f(aa)    |
   = 0.5      |   = 0.25  |   = 0.25   |
              |           |            |
              |           |            |
              --------------------------
      1. Note how the above ratios work out to:
        1. 1:1:1:1 or f(AA) : f(Aa) : f(aA) : f(aa).
        2. 1:2:1 or f(AA) : f(Aa)=f(aA) : f(aa).
        3. 3:1 or f(A phenotype) : f(a phenotype).
      2. with the third example true only for a alleles which are recessive to A alleles.
  1. Allele frequency (is different from genotype frequency)
    1. Going from genotype frequency to allelic frequency:
      1. Theoretically, at least, it is possible to count up all of the individuals that have one combination of alleles at a given loci and determine the frequency of this combination among the rest of the population.
      2. From this frequency of all of the genotypes found in a population it is possible to determine the frequency of all of the alleles found in the population.
    2. Example: calculating allele frequency from genotype frequency:
      1. If 0.25 of the population is Aa, 0.50 AA, and 0.25 aa, then the frequency of the A allele is (0.25 + 0.00 + 0.50 + 0.50 + 0.00 + 0.00) / (0.25 + 0.25 + 0.50 + 0.50 + 0.25 + 0.25) = 1.25 / 2 = 0.63.
      2. This is how one determines the frequency of alleles in Punnett squares.
      3. Note how 0.63 compares with your knowledge that the A allele is carried by 75% of the individuals in the example population (i.e., f(Aa) + f(AA))
  2. Dihybrid
    1. A dihybrid individual is one which is heterozygous at two different loci.
    2. Complicated genetics:
      1. A stepwise increase in complication occurs when one starts considering multiple alleles located at multiple loci.
      2. Consider an A and a allele existing at the A loci and a B and b allele exist at the B loci. In such a case, possible diploid genotypes include AABB, AaBB, aaBB, AABb, AaBb, aaBb, AAbb, Aabb, and aabb.
      3. Note that only the fifth member in the above example is considered a dihybrid.
    3. Gamete genotypes:
      1. Continuing with the example presented above, note that the haploid gametes of a dihybrid would include AB, Ab, aB, and ab.
      2. Note also that only those diploid individuals carrying the appropriate alleles are actually capable of producing a given gamete. For example, an AABb individual could give rise to an AB and an Ab but not an aB or an ab.
    4. Independent assortment:
      1. Furthermore, assuming independent assortment of chromosomes, and locus A not being found on the same chromosomes as locus B, then an AABb individual would be expected to give rise to two AB and two Ab gamete per meiotic division.
      2. In fact, the term independent assortment was not originally coined to describe the meiotic process, but instead to describe this consequence of gamete formation by a dihybrid individual.
  3. Linkage [syntenic loci]
    1. In a dihybrid, if locus A and locus B are found on the same chromosome (i.e., they are syntenic) then only recombination can separate these alleles.
    2. P(assortment) = f(distance between loci):
      1. If two loci are found sufficiently close on the same chromosome then the likelihood that recombination will separate the associated alleles is much lower than the likelihood that two alleles will separate into different gametes if they are found on two different chromosomes (or even far apart on the same chromosome).
      2. Consequently, two alleles sharing the same chromosome are said to be linked, and the degree of linkage is a function of how physically close the loci are on the chromosome.
  4. Linkage map
    1. Distance inferred from linkage:
      1. Because the degree of linkage appears to be well correlated with distance on a chromosome, measurements of linkage can be used to estimate distance between loci found on the same chromosome.
      2. Such maps of chromosome are very commonly employed in genetic studies.
  5. Genetic map
    1. Equivalent to a linkage map except obtained by means other than (or in addition to) studies of rates of recombination (i.e., degrees of linkage).
    2. Currently investigators are hard at work attempting to elucidate a genetic map of the entire human genome.
  6. Epistasis [epistatic]
    1. No entry.
  7. Overdominant
    1. No entry.
  8. Pleiotropy [pleiotropic]
    1. No entry.
  9. Polymorphism [polymorphic]
    1. No entry.
  10. Semidominance [incomplete dominance]
    1. No entry.
  11. Vocabulary
    1. Allele
    2. Allele frequency
    3. Cross
    4. Dihybrid
    5. Dominant
    6. Gene
    7. Genome
    8. Genotype
    9. F1 generation
    10. F2 generation
    11. Hereditary material
    12. Heterozygote
    13. Homozygote
    14. Linkage
    15. Locus
    16. Mendelian ratio
    17. One gene, one polypeptide
    18. Phenotype
    19. Punnett square
    20. Recessive
    21. Self
    22. Wild type
  12. Practice questions
    1. Given a two allele, one loci system in which the frequency of genotype Aa is 0.25, a frequency of genotype aa of 0.50, and A is dominant to a, then what is the frequency of the phenotype associated with allele A? What is the frequency if instead A is recessive to a? [PEEK]
      1. 0.25, 0.25
      2. 0.25, 0.50
      3. 0.50, 0.25
      4. 0.50, 0.50
      5. none of the above
    2. Is a cross between an AABb individual and an AaBB individual capable of producing a dihybrid? If so, how many of the progeny would expect to be dihybrids? Possible bonus question: If you allowed random mating within a population containing 40% AABb individuals and 60% AaBB individuals, what fraction of the progeny would you expect to be dihybrids (the answer to this bonus question is not included among the multiple choice answer below)? [PEEK]
      1. no
      2. yes, 10%
      3. yes, 25%
      4. yes, 50%
      5. yes, 75%
      6. yes, 80%
      7. none of the above
    3. A mating between two dihybrid individuals yields progeny which are 16% AABB, 8% AABb, 1% AAbb, 8% AaBB, 34% AaBb, 8% Aabb, 1% aaBB, 8% aaBb, and 16% aabb. Assume no evolution. This is an example of _________________. [PEEK]
      1. linkage
      2. a Mendelian ratio
      3. selfing
      4. non-syntenic loci
      5. none of the above
      6. all of the above
  13. Practice question answers
    1. iii, 0.50 for A dominant and 0.25 for A recessive.
    2. iii, yes, 25%; bonus question answer: 12%.
    3. i, linkage; here's where the frequencies came from:
      1. AaBb x AaBb
      2. Assume that the A and B are linked (and therefore a and b are linked).
      3. Furthermore, assume that linkage is not complete such that 80% of meiosis products remain linked while 20% do not.
      4. In that case, the following gametes would be produced (with frequencies shown parenthetically): AB (40%), Ab (10%), aB (10%), ab (40%).
      5. Working all this through a Punnett square givens F1 genotype frequencies:
       |  AB        Ab        aB        ab  
       |  0.40      0.10      0.10      0.40
-------|------------------------------------
AB     |  AABB      AABb      AaBB      AaBb
0.40   |  0.16      0.04      0.04      0.16
       |                                    
Ab     |  AABb      AAbb      AaBb      Aabb
0.10   |  0.04      0.01      0.01      0.04
       |                                    
aB     |  AaBB      AaBb      aaBB      aaBb
0.10   |  0.04      0.01      0.01      0.04
       |                                    
ab     |  AaBb      Aabb      aaBb      aabb
0.40   |  0.16      0.04      0.04      0.16
      1. From the above genotype frequencies can be calculated:
      2. AABB = 0.16 = 16%
      3. AABb = 0.04 + 0.04 = 0.08 = 8%
      4. AAbb = 0.01 = 1%
      5. AaBB = 0.04 + 0.04 = 0.08 = 8%
      6. AaBb = 0.01 + 0.01 + 0.16 + 0.16 = 0.34 = 34%
      7. Aabb = 0.04 + 0.04 = 0.08 = 8%
      8. aaBB = 0.01 = 1%
      9. aaBb = 0.04 + 0.04 = 8%
      10. aabb = 0.16 = 16%
      11. Note that this all is an example of what is known as linkage disequilibrium. I.e., a bias is shown in a population toward the linkage of certain alleles (e.g., AB rather than aB). Each generation the population will be drawn toward less and less of a bias since linkage is not complete. The population will therefore eventually reach equilibrium where there will be no bias. Thus, the population as described above is in linkage disequilibrium.
      12. The fact that ratios of F1 genotypes are not what you expect, and no evolution is going, is suggestive of linkage disequilibrium which, of course, is suggestive of linkage.
  1. References
    1. Raven, P.H., Johnson, G.B. (1995). Biology (updated version). Third Edition. Wm. C. Brown publishers, Dubuque, Iowa. pp. 231-257.