Extensions to Mendelism

8/3/2019 Extensions to Mendelism

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Extensions to Mendelism

Mendel's pea experiments used a very

simple genetic system: each gene had 2

alleles, one dominant and one recessive,

and genes did not interact with each other.

We are going to look at some variations:

different forms of dominance, multiple

alleles, interactions between genes, andenvironmental effects.


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Partial (Incomplete) Dominance

Mendel studied complete dominance: theheterozygote looks exactly like the dominanthomozygote.

In partial dominance, the heterozygote has

phenotype intermediate between the twohomozygotes.

Example: Four o'clock plants. Red flowers xwhite flowers gives pink F1's. Pink is

intermediate between red and white. Selfing the F1's gives 1/4 red (RR), 1/2 pink (Rr),and 1/4 white (rr)


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Co-dominance

In co-dominance, both parental alleles are expressed in theheterozygote.

Example: blood groups. Antigens on the surface of red blood cellscause them to clot in the presence of the corresponding antibody.

The MN blood group antigens are coded for by the L gene: the 2

alleles are called LM

and LN

. A LM LM homozygote has the M blood type: blood clots in thepresence of anti-M antiserum, but not in the presence of anti-Nserum.

Similarly, a LN LN homozygote has the N blood type: blood clots inthe presence of anti-N antiserum, but not in the presence of anti-M

serum. The LM LN heterozygote has the MN blood type: it clots with bothanti-M and anti-N antiserum. These red blood cells have bothantigens on their surface. Thus, the MN blood group alleles are co-dominant.


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Electrophoresis

When an organism's DNA or proteins are examined closely, almostall genes are co-dominant. Both alleles of the gene are present,even if they don't contribute equally to the phenotype.

Electrophoresis is a way of separating the DNA of the genes or theproteins the genes produce.

Electrophoresis depends on a fundamental physical property:charged objects move in an electric field. DNA and RNA have one negative charge per nucleotide. Most

proteins also have a net negative charge, caused by 2 of the 20amino acids, which have a negative charge. Since oppositecharges attract, most nucleic acids and proteins move towards thepositive pole.

The speed the molecules move is proportional to their charge andinversely proportional to their size: small, highly charged moleculesmove faster than large, less charged molecules.

Electrophoresis is done in a gel matrix, to prevent diffusion fromconfusing the results.


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More Electrophoresis

As an example, the enzyme "phosphatase" removes phosphategroups from other molecules. When an extract is made of theproteins in an organism, it is possible to separate the proteins byelectrophoresis and then stain the gel so only the phosphatase willappear.

In this example, there are 2 alleles of the gene that makesphosphatase. One allele puts more negatively charged amino acidson the protein's surface than the other allele does. Thus, one alleleproduces a more highly charged protein that moves faster inelectrophoresis than the less charged protein from the other allele.These two alleles are called F (Fast) and S (Slow).

After electrophoresis and staining of the gel, an FF homozygote

shows a single band, far down the gel. The SS homozygote showsa single band that has only moved a little ways down the gel. TheFS heterozygote shows both the F band and the S band. Thismeans that the phosphatase gene is co-dominant: the heterozygoteshows both parental types.


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Multiple Alleles

Mendel used only 2 alleles per gene. Anychange in the DNA sequence of a gene is adifferent allele, so there are millions of possiblealleles for any gene.

In reality, many genes have several commonalleles: they are polymorphic. Some genes areconstrained by natural selection to have only asingle allele: they are monomorphic. Having 2alleles, as in Mendels genes, is calleddimorphic.

Genes with multiple alleles can have a variety ofdominance patterns between the alleles.


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ABO Blood Group

The ABO blood group is a common multiple allele system.The gene itself is called I, and it has 3 alleles: IA, IB, andiO.

IA and IB are co-dominant, and both IA and IB aredominant to iO.

Thus, IA IA homozygotes and IA iO heterozygotes have typeA blood.

Similarly, IB IB homozygotes and IB iO heterozygotes havetype B blood.

Because IA

and IB

are co-dominant, IA

IB

heterozygoteshave AB blood. Type O blood occurs in people with the iO iO genotype. Note: O is the most common blood type. Frequency in

the population is not related to dominance.


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Major Histocompatibility Locus

The MHC is the primary determinant of human tissue type, whichdetermines whether organs can be transplanted between peoplewithout rejection by the immune system.

The MHC consists of 6 major genes lying close together on onechromosome. These genes are usually inherited as a single unit,called a "haplotype". Taken together, the MHC genes are probablythe most polymorphic region of the human genome. There arethousands of known haplotypes.

Most people have 2 different haplotypes, one inherited from eachparent. Similarly, mates usually have different haplotypes. Theresult of this is that each person has one haplotype in common witheach parent and one haplotype different. However, a person has a

1/4 chance of having both of the same haplotypes as his/her sibling.Thus, organ transplants between siblings are usually the easiest to

perform.


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More Lethal Alleles

Lethal alleles give an unusual inheritance ratio. Considera mating between two Manx cats. Each is heterozygousTt, with T the dominant tailless allele and t the recessivenormal tail allele.

Using Mendel's Law of Segregation, we see that zygotesform in the ratio of 1/4 TT, 1/2 Tt, and 1/4 tt.

However, all the TT embryos die at a very early stage,and only the Tt (tailless) and tt (tailed) cats are born.

Because there are twice as many Tt as tt, the ratio ofoffspring in the Tt x Tt cross is 2/3 Tt (tailless) to 1/3 tt(tailled).

Note that pure breeding lines of Manx cats (andachondroplastic dwarves) can't exist, because 1/3 of theiroffspring are of the incorrect type.


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Interactions between Two Genes

More than one gene can affect the same

trait. Lots of possible interactions: we will

look at a few, using only 2 genes and

complete dominance for both.


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Two Genes

1. Two dominant alleles necessary for the trait. Example:pea purple vs. white flowers. Mendel looked at one gene,but there is another that is also necessary.

Call the genes A and B. Both have two alleles: A and a, Band b. To get a purple flower, the plant must have both aA allele and a B allele.

Selfing a double heterozygote Aa Bb gives 9/16 A_ B_,3/16 A_ bb, 3/16 aa B_, and 1/16 aa bb. Only the 9/16 A_B_ have both an A allele and a B allele: these are purple.The rest are white.

The final ratio is thus 9/16 purple to 7/16 white. Also worth noting: AA bb x aa BB is a cross between two

white plants. However, the offspring are all Aa Bb =purple.


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Two Genes

2. Duplicate genes. Thedominant allele from at leastone of the two genes isneeded to give the dominantphenotype.

Example: the plant "shepherd'spurse" (Capsella bursa-pastoris, in the mustardfamily). To get a triangularseed pod, you must have adominant allele from either the

A gene or the B gene. Thealternative is an ovoid seedcapsule.

Thus, the offspring of a selfedAa Bb plant give 15/16triangular (9/16 A_ B_, 3/16 A_bb, 3/16 aa B_) and 1/16 ovoid

(aa bb).


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Two Genes

3. Two genes withdifferent effects on thetrait. Chicken combtypes.

Here we have: top left ="pea" comb, from aa B_genotype. Top right ="rose comb", from A_ bbgenotype. Bottom left =

"single comb", from aa bbgenotype. Bottom right ="walnut comb", from A_B_ genotype.


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Two Genes

Epistasis. One gene controls the expression of anothergene.

Example: albinism and coat color in dogs. An albino doglacks all pigment, so it is white. The albinism gene has

two alleles: C (normal color) and c (albino). Another genecontrols black vs. brown: B is the dominant black allele,and b is the recessive brown allele.

If two Bb Cc dogs are mated (both are black), 9/16 of theoffspring are B_ C_ (black), 3/16 are bb C_ (brown), and

4/16 are __ cc (white). The cc dogs can be BB, Bb, or bb:it doesn't matter because the expression of the coat colorgene is controlled by the albino gene.


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Penetrance and Expressivity

Expression of many genes is affected by the environmentor by "background" genetic influences. Two closelyrelated concepts are used to describe this.

Penetrance is the percentage of offspring with the mutantgenotype that express the mutant phenotype.

Expressivity is the degree to which the mutant phenotypeis expressed.

Example. Polydactyly is having extra fingers and toes.There are several forms of this condition. For one form,polydactyly is 65% penetrant: 65% of those who carry thedominant polydactyly allele have extra digits. Examiningthese people, there is a range of expression: some have 1extra digit, some have 2, etc. Also, some of the digits arefunctional: have proper bones, muscles and nerves, whileothers are missing vital components or connections.


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Polydactyly

Alfredo Alfonseca

"The Six Shooter",

former Chicago Cubs

relief pitcher. Six fingers and toes

on each hand, all

functional.


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Environmental Effects

Many traits are affected bythe environment as wellas by genetics.

For example, the

hydrangea flower color iscontrolled first by flowercolor genes similar tothose in the pea: purplevs. white with complete

dominance. But, pink vs.purple is controlled by theacidity of the soil in whichthe plants grow.


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Phenocopies

A phenocopy is an organism that has a mutantphenotype but a normal (wild type) genotype. Itgot the mutant appearance through anenvironmental cause.

Drugs that cause birth defects are a commoncause. Nothing is genetically wrong with thechild, but it was exposed in utero to toxicchemicals

Another example: my cat Angel, whose tail gotrun over by a car, looks like a Manx cat(genetically tailless), even though she startedout with a normal tail.


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Pleiotropy

Pleiotropy is one gene affecting several traits.

This is quite common: genes make proteins and

often affect the overall phenotype in subtle ways

that affect many different body systems. Example: sickle cell anemia causes enlarged

spleen, muscle pain, low red blood cell count,

resistance to malaria, and early death. All of this

is caused by a single mutation in one of thehemoglobin genes.

Extensions to Mendelism

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