Biology Dept
Kenyon College
Chapter 3.
Gene Product Interaction, Crossover, Mobile Genes
Fall Section Spring Section 1 Spring Section 2
Gene product interaction

In real living organisms, all traits result from the interaction of many gene products.  Suppose two enzymes are required to produce a trait.  What may be the result?  What will happen to Mendelian inheritance ratios?

  • Recessive epistasis.  The presence of recessive alleles at one locus makes useless the presence of dominant alleles at another locus.  This happens if two enzymes are needed in series; "the chain breaks" if either link fails.  The Mendelian ratio of a dihybrid cross is 9:7.
  • Dominant epistasis.  The presence of one dominant allele at one locus compensates for the lack of dominant alleles at the other locus.  If it works in both directions, the ratio from a dihybrid cross is 15:1.
PROBLEMS: Solutions

1. In sweet peas, purple is dominant; white is recessive.  Suppose two recessive white flowers from different breeders are cross-bred together.  The flowers--surprise--show the dominant purple color.  When self-crossed, the ratio is 9 purple: 7 white.  Explain these results.

2.  In fancy fowl, feathers are dominant to non-feathered.  Two pure-breeding feathered birds from two different fowl fanciers are bred, producing lovely feathered offspring.  The offspring are intercrossed, and a few of their offspring have no feathers.  The ratio is:
15 feathered: 1 non-feathered.  Explain these results.

3. Beetle colors. 

Suppose the color of beetles is determined by this enzyme pathway.  Enzymes A and B are needed in series, but enzyme C represses enzyme A.

Figure out what dihybrid crosses would produce what ratios.  Remember that you have to specify the entire genotype, including the purebreeding locus; for instance:
AABbCc would be a dihybrid cross for B and C, but AA would be the same for all offspring.

  •   9   : 4  : 3 
  • 12   : 3  : 1 
  • 13  : 3 


Complementation refers to the fact that mutations producing null alleles in different genes can be complemented, or compensated in effect, by the gene product provided elsewhere.  An example of complementation is two-way recessive epistasis: The two white strains of sweet pea complement each other:

P1 P1 p2 p2   X   p1 p1 P2 P2  -->  P1 p1 P2 p2  (purple flowers)

You can use complementation analysis to intercross a large number of independently isolated null phenotypes, and figure out how many different genes are required for the enzyme pathway to produce the phenotype.

See the MIT site on Complementation. 

Non-Mendelian Inheritance

Some forms of inheritance complicate the pattern of Mendelian inheritance and reassortment of traits.  Inheritance may be overlaid by expansion of triplet repeats, or by parental imprinting.  A  few genes are not inherited by Mendelian principles at all, because they are contained on an extranuclear chromosome of the mitochondria or chloroplast.

Microsatellite expansion

A well-known example is Fragile X Syndrome.  This very common cause of mental retardation results from a region of repetitive DNA sequence that grows longer than normal with each generation.  The length of the sequence--a multiple triplet repeat, called a microsatellite--encourages the region of the chromosome to shut down expression of an essential FMR1 gene nearby.  It also makes the chromosome "fragile;" that region of the chromosome fails to condense during cell culture for karyotyping.  Fragile X shows incomplete dominance; females who carry the trait will show partial (but not total) compensation by the wild-type allele on the other X chromosome.
Check here for research on Fragile X.

Imprinting and DNA methylation

So far, all the inheritance mechanisms we have considered depend on DNA sequence of bases: A, T, C, G.  However, certain sequences in addition contain chemical modification such as methylation.  These modifications are added after DNA replication.  They add information about how a gene will be expressed.

In mammals, methylation occurs in the gonads, as sperm or eggs develop.
The male and female produce DIFFERENT patterns of methylation.  This means that the degree of expression of a trait may be different, depending on which parent you have inherited the trait from--even though the trait is completely autosomal.

For example Huntington's disease is autosomal dominant.  The onset of disease may occur in childhood, if you inherit the trait through your father; but only much later in life, if you inherit through your mother.

Another disease involving methylation is Fragile X Syndrome.  (See your handout.)  In Fragile X, a region of repetitive CGG sequence is too long.  The length of the repetitive sequence stimulates enzymes to "turn off" expression, including a nearby essential gene, FMR-1.  This sequence is "turned off" through methylation in the female, and fails to get "turned back on" in her children.  Children of males do not show the syndrome; but the grandchildren have high risk.

Extranuclear Chromosomes

Outside the nucleus are the mitochondria, which evolved out of endosymbiotic bacteria.  Plants in addition havechloroplasts which arose the same way.  Mitochondria  have small circular chromosomes which are inherited through the female, because the sperm contribute no mitochondria to the fertilized egg.

A mother passes on mitochondrial traits to all of her children.  Some Mitochondrial Diseases  have been identified, including muscle degeneration and some forms of migraine headache.

Recombination by Crossover of Chromosomes

Two DNA helices may "cross over" or recombine, a process requiring breakage of each strand at the phosphodiester backbone and ligation to another strand.  There are two different classes of recombination:

  • Homologous recombination occurs when two homologues (regions of nearly identical gene sequence) associate and exchange.  This type of recombination can occur with many different sequences, but the two sequences which actually recombine must be nearly identical.
  • Site-specific recombination occurs when a gene (or phage genome, or plasmid) needs to insert itself into (or excise itself out of) a larger genome.  This recombination involves little or no homology, but involves enzymatic recognition of a particular short DNA  sequence.
In either case, recombination does not happen by itself.  It is mediated by recombinase enzymes.  These enzymes bind to DNA; cleave and protect single-stranded DNA; and mediate the transfer of a single-stranded end to the recombining duplex.  To visualize a recombinase enzyme interacting with DNA, visit this example, the hin recombinase.

Problem:  Is hin recombinase involved in homologous recombination, or site-specific recombination?  Explain your answer.

Homologous recombination

This image series shows how two homologous chromosomes within a tetrad cross over and exchange portions of their arms. (Problem: What phase of meiosis?)  The blue and red arms designate homologues from different parents.  (Why are they each double already?)Click the image:

Linkage and Mapping

What happens to Mendelian ratios when two genes are linked on the same chromosome?

  • Random reassortment.  If the map positions, or loci, of the two genes are far enough apart so that many crossovers occur between them, then they may appear to reassort independently, with Mendelian ratios.  This is actually what happened with several of Gregor Mendel's pea traits.
  • Deviation of ratios--"parental" vs. "recombinant."  If the loci are near enough so that recombination is less than 50%, then linkage will be favored for the pattern of alleles that was the same for each parent.
Consider these two crosses, for traits with 10% recombination.

                 A    B            a    b                             A    b            a    B
Parents         --------     X    -------                            --------     X    -------
                A    B            a    b                       A    b            a    B

                             A    B                                         A    b
F1                               --------    < Same phenotype! >    --------
                                    a    b                                          a    B

Test Cross                       45%         A    B           5%
with  a    b                                         ---------
         --------                                           a    b
          a    b
                                   45%          a    b      5%
                                                     a    b

                                               5%       A b             45%
                                                              a    b

                                               5%       a    B       45%
                                                              a    b

Which classes are "parental"?  "Recombinant"?

Map Distances.
For distances <10%, where the proportion of double crossovers is small, the rate of recombination is approximately proportional to the physical distance along the DNA helix.   So one can map the order of genes on a chromosome by intercrossing strains with closely linked markers.
1% recombination = 1 map unit

Problem: What happens when there are double crossovers?  How does this interfere with map calculations?

To practice gene mapping, try out Virtual Fly Lab.  Problem: Try crossing female Stubble, Aristapedia with male wild type. Explain your results.   (Note: both Stubble and Aristapedia traits have to start out hybrid, because the double dominant is lethal.)

LOD scores and pedigrees.
Today we use statistical analysis of human pedigrees to calculate the linkage between particular diseases and regions of DNA that may contain the gene for the disease.  The "log of the odds" (LOD) score yields the probability of a given recombination frequence for a given set of pedigree data.

Mobile genes.
Some genes, such those encoding resistance to antibiotics, can move from one genome to another, at a new place in the genetic map.  Some of these mobile genes can even transfer between two distantly related species of organism.

Transposable elements
The first transposable elements to be characterized genetically were controling elements for seed coat color in maize (corn.)  Barbara McClintock won the Nobel Prize for showing that DNA is not all "fixed" in the genome, but that some sequences can insert and excise by intramolecular recombination.

Images below are from

Electronic Companion to Genetics, Cogito Learning Media

There are  many classes of transposons.  In bacteria, a common structure of a transposon contains:
  • An insertion sequence (IS) at the right and left ends.  The IS contains the gene encoding the transposase enzyme.

  • A gene encoding antibiotic resistance.  This gene confers a selective advantage to bacteria containing the transposon, in  the presence of the antibiotic.
Some bacterial transposons can be exchanged among many different species, usually carried by plasmids.
Other transposed pieces of DNA can be inverted at one place in one species, to turn on or off the regulation of a gene.  An example of such a site-specific transposition event is the flagellar gene regulation catalyzed by hin recombinase.

Bacterial Gene Transfer

Bacterial gene exchange differs from eukaryotes:

  • Bacteria do not exchange genes by meiosis.  (Why not?)  They rarely exchange two entire genomes.
  • Bacteria commonly exchange small pieces of genome, a few genes at a time, through transformation, transduction, or conjugation.
  • Transfer between species, even kingdoms, is common; less common  in eukaryotes, though it does occur.
Transformation is the uptake of DNA from outside the cell.  Only a single strand is taken up, through a special protein  complex in the cell membrane.  The process requires calcium ion (Ca2+).  Transformation occurs at extremely low frequency, but with large populations of bacteria, it offers a significant route for genetic transfer.

Phage Transduction
There are two types"

  • Generalized transduction (depicted below).  A piece of host DNA gets packaged by mistake, instead of the phage DNA.  This rare event results in a phage delivering only bacterial DNA to the next host.  The DNA then recombines homologously, replacing the host allele.
  • Specialized transduction, in which a lysogenic prophage recombines itself out of the genome (by site-specific recombination) and mistakenly includes a piece of bacterial DNA.  The resulting phage progeny can infect cells to produce lysogens with a second copy of the allele they had packaged, attached to the phage DNA.
Diagram of generalized transduction:


Plasmids are small circles of DNA that contain an origin of replication (ori) and a small number of genes, some of which may confer a survival advantage on a host.  Some plasmids can transfer between different species; even between different kingdoms.  A shuttle vector is a plasmid engineered in the test tube to contain an ori site for bacteria, and an ori site for animal or plant cells.  Shuttle vectors are enormously useful to clone a gene conveniently in bacteria, then express it in tissue culture.


Conjugation is the process by which a plasmid is transferred from an F+ cell into an F- cell.  The F factor in the F+ cell contains genes which express pili for attachment, and special membrane proteins for the transfer complex.  Some conjugative plasmids carry drug resistant strains--a big problem for hospitals.

If an F plasmid is integrated into a host genome (an Hfr, for high frequency recombination) the F factor can transfer part or all of the genome into the recipient F- cell.

Electronic Companion to Genetics, Cogito Learning MediaI
Episomes and Hfr
The F plasmid can recombine itself into the host chromosome by site-specific recombination.  It can then (a) transfer part or all of the chromosome into a recipient F- cell, as an Hfr; or (b) recombine itself out again, and mistakenly pick up a piece of the host chromosome to carry into the next F- host.

Problem (5)  Explain two different genetic processes in bacteria that can create a "partial diploid" for a small part of the genome.  Explain why these processes are useful for bacterial genetic analysis.

Interesting sites on bacterial genetics: