©2000 Timothy G. Standish Jeremiah 23:24 24Can any hide himself in secret places that I shall not see him? saith the LORD. Do not I fill heaven and earth?

©2000 Timothy G. Standish

Jeremiah 23:24

24Can any hide himself in secret places that I shall not see him? saith the LORD. Do not I fill heaven and earth? saith the LORD.


Beyond MendelBeyond Mendel

Timothy G. Standish, Ph. D.


Some traits, when they are tested using Mendel’s techniques, do not produce a 3:1 or 9:3:3:1 ratio Example: When disk shaped and long summer squash are crossed they result in a F2 phenotypic ratio of

9/16 disk, 6/16 sphere and 1/16 long; a 9:6:1 ratio instead of the expected 9:3:3:1 or 3:1 In such cases it is not necessary to abandon Mendel’s basic principle of independent assortment of

genes or the chromosome theory that genes occupy specific loci on chromosomes However, a more subtle understanding is necessary of genes, gene products and alleles

When The Ratios Are WrongWhen The Ratios Are Wrong


Exceptions to Mendelian ratios may be accounted for in the following ways:

1 Incomplete or codominance - Two or more alleles exist, but none is dominant to the other/s

2 Multiple alleles for a single gene3 Epistasis - In which interactions between more than one

gene result in a trait4 X-linkage - In which the locus of a gene is on the X

chromosome5 Sex influenced or limited genes, where expression is

influenced or limited by gender or environment

ExplainationsExplainations


Incomplete or codominance - Two or more alleles exist, but none are dominant to the other

Incomplete dominance results in blending of the parental traits

Example: In four O’clock flowers (and others) red crossed with white results in pink F1 progeny

1 Incomplete Or Codominance1 Incomplete Or Codominance

XX


F2 results show this is not blended inheritance


F1P

XX

CRCWCRCR CWCW

CRCR

CRCW

CRCW

CWCW

CR CW

CR

CW

F2 GenerationF2 Generation

2: 11:

In the F2 generation a 1:2:1 ratio results of red to pink to white


ErythrocyteErythrocyte

Membrane

Cytoplasm

Codominant traits show up clearly whether the other allele is present or not

Example: MN blood group genes in humans are codominant


M

M

M

M antigen

Anti M antibodies

M phenotypeMM genotype



Membrane

Cytoplasm




N antigen

Anti N antibodies

N phenotypeNN genotype

N

N

N



Membrane

Cytoplasm




M

M

M and N antigens

Anti M antibodies

MN phenotypeMN genotype

NAnti N antibody


2 Multiple Alleles2 Multiple Alleles Any gene with two or more alleles is said to have

multiple alleles Mendel worked with only two allele systems, but

variations from the kind of results he obtained occur when more than two alleles are involved

Note that while individuals cannot have more than two alleles for a given gene, populations can have many different alleles

Human ABO blood types provide an excellent example of multiple alleles in human populations


2 Multiple Alleles2 Multiple Alleles ABO blood types are determined by the presence of antigens

on the surface of erythrocytes in much the same way as MN blood types

The antigens are oligoscaccharides presented on the cell surface

Almost everyone makes an oligosaccharide called “H substance” which is a chain of sugars joined together in the following order:

L-fructose ˜ b galactose ˜ N-acetylglucosamine Individuals with O type blood only display the H substance on

their erythrocytes


2 Multiple Alleles2 Multiple AllelesType A and B blood result from the presence

of enzymes which add a sugar to the H substance

Type A individuals produce an enzyme that adds N-acetylgalactosamine to the galactose in the H substance

Type B individuals express a very similar enzyme that adds galactose to the same place


2 Multiple Alleles2 Multiple Alleles If neither enzyme is expressed type O blood results If the N-acetylgalactosamine adding enzyme is

present type A blood results If the galactose adding enzyme is present type B

blood is made If both the N-acetylgalactosamine and galactose

adding enzymes are present, type AB blood results As the enzymes are coded for by genes, blood type is

under direct genetic control


When a single trait is controlled by more than one gene epistasis may result

The squash example we started with is an example of epistasis

Understanding biochemical pathways helps us understand epistasis

EpistasisEpistasis

B CA 21 DC

A3

1

D2

B


EpistasisEpistasis

B CA 21

If the gene for enzyme 1 was knocked out, the flower would be colorless

B CA 21

X

Imagine that this pathway produces a red pigment, C, in flowers and that A is a colorless precursor and B is a yellow intermediate


EpistasisEpistasis

B CA 21

If the gene for enzyme 1 was knocked out, the flower would be colorless

B CA 21

X

Imagine that this pathway produces a red pigment, C, in flowers and that A is a colorless precursor and B is a yellow intermediate

If the gene for enzyme 2 was knocked out, the flowers would be yellow


EpistasisEpistasis

B CA 21

Because enzymes can catalyze many reactions in a short period of time, the presence of just one copy of a gene is typically enough to mask the absence of a bad copy

Thus an individual heterozygous for enzyme 1 could still produce intermediate product B

B CA 21X X

If both genes were knocked out, the flowers would be colorless


Consider a cross between a two individuals heterozygous for both enzyme coding genes

Lets call the functional enzyme 1 gene 1F and the mutated gene producing nonfunctional enzyme 1, 1n

We will use the same convention for enzyme 2 with genes 2F and 2n

Our cross would look like this:

EpistasisEpistasis

1F1n2F2n X 1F1n2F2n


11FF11nn22FF22nn XX 11FF11nn22FF22nn

1F2n

1n2F

1n2n

1F2F

1n2n1n2F1F2n1F2F

1F1n2F2n1F1n2F2F1F1F2F2n

1F1n2n2n1F1n2F2n1F1F2n2n1F1F2F2n

1n1n2F2n1n1n2F2F1F1n2F2n1F1n2F2F

1n1n2n2n1n1n2F2n1F1n2n2n1F1n2F2n

1F1F2F2F


11FF11nn22FF22nn XX 11FF11nn22FF22nn

1F2n

1n2F

1n2n

1F2F

1n2n1n2F1F2n1F2F

1F1n2F2n1F1n2F2F1F1F2F2n

1F1n2n2n1F1n2F2n1F1F2n2n1F1F2F2n

1n1n2F2n1n1n2F2F1F1n2F2n1F1n2F2F

1n1n2n2n1n1n2F2n1F1n2n2n1F1n2F2n

1F1F2F2F


– 10:3:3 = (9+1):3:3– 10:6 = (9+1):(3+3)– 13:3 = (9+1+3):3

A 9:4:3 RatioA 9:4:3 Ratio

– 9:7 = 9:(3+3+1)– 12:3:1 = (9+3):3:1– 12:4 =(9+3):(3+1)

A ratio made up of some combination of 9:3:3:1 is generally a good hint that epistasis is at work

A biochemical pathway like the one discussed will result in a 9:4:3 ratio as long as there are two alleles each of which behaves in a simple dominant/recessive way

The 9:4:3 ratio is really a 9:(3+1):3 ratio Other possible phenotypic ratios for a

dihybrid cross involving epistasis include:


Agouti Mice - A 9:4:3 RatioAgouti Mice - A 9:4:3 Ratio

Mice lacking yellow or black are albino

Brown mice actually exhibit agouti coloration, a mix of yellow and black with hair strands alternating yellow and black melanin pigment

Yellow Black AlbinoAgouti

Mutating a gene coding for an enzyme necessary to make black pigment results in yellow mice

Mutating an enzyme for yellow results in black



ColorlessPrecursor

YellowY

AgoutiB

Black

ColorlessPrecursor

Yb

yB

yb

YB

ybyBYbYB

YyBbYyBBYYBb

YybbYyBbYYbbYYBb

yyBbyyBBYyBbYyBB

yybbyyBbYybbYyBb

YYBB

ColorlessPrecursor

Y Agouti/Yellow

BBlack

Two possible explanations of agouti


Cross two agouti individuals who

are both heterozygous

YyBb X YyBb



ColorlessPrecursor

YellowY

AgoutiB

Black

ColorlessPrecursor

Yb

yB

yb

YB

ybyBYbYB

YyBbYyBBYYBb

YybbYyBbYYbbYYBb

yyBbyyBBYyBbYyBB

yybbyyBbYybbYyBb

YYBB

BlackAgouti/Yellow

ColorlessPrecursor

YB



Cross two agouti individuals who

are both heterozygous

YyBb X YyBb


As mentioned earlier, the F2 generation of a cross between a disk shaped and a long squash has a disk:spherical:long ratio of 9:6:1

How can this ratio be explained? In the F2 generation the following genotypes

must result in the indicated phenotypes

Another Example Of Epistasis:Another Example Of Epistasis:Fruit Shape In Squash, A 9:6:1 RatioFruit Shape In Squash, A 9:6:1 Ratio

9 A_B_3 A_bb3 aaB_1 aabb Long

Disk

Sphere


4 X-Linkage4 X-Linkage Thomas Hunt Morgan was the first to associate a trait

(gene) with a chromosome. Worked with fruit flies (Drosophila melanogaster) In humans and Drosophila, males are XY Thus males are haploid for the X chromosome Because of this, recessive genes on the X chromosome

show up far more commonly in male than female phenotypes


DrosophilaDrosophila Nomenclature Nomenclature

+ = Wild type, phenotype in nature (i.e. red eyes and round wings)

Mutants are alternatives to the wild type Fruit fly genes are named after the mutant Dominant mutations are capitalized (i.e. Hairless or

H and Bar or B) Recessive mutants are named using lower case

letters (i.e. black or b and white or w)


Sex DeterminationSex Determination Two ways in which sex can be determined: Environment:

Turtles - Temperature of development Some fish - Social structure

Chromosomes - Three methods: XO - Haploid/diploid ie bees, haploid males diploid females ZW - Heterogametic (ZW) females, homogametic (ZZ) males, ie

birds XY - Heterogametic (XY) males, homogametic (XX) females, ie

humans and Drosophila


Morgan’s Discovery Of An X-Morgan’s Discovery Of An X-Linked Linked DrosophilaDrosophila Gene Gene

A white-eyed male was discovered

X+ X+

X+Y

Xw X+

XwY

X+ Xw

X+

Y

Xw X+

X+Y

Xw X+

X+Y

X+ X+

Xw

Y

X P

X F1

F2

1/21/4 1/4


The Key To Morgan’s DiscoveryThe Key To Morgan’s Discovery The key to Morgan’s discovery was the observation that all

the white eyed individuals in the F2 generation were males

Without this vital data on the association of white eyes with being male, the gene for white eyes could have been seen as a simple recessive trait on an autosome

This illustrates the importance of recording all the data possible and being alert to the possibility of interesting things being present in the data

“Fate favors the prepared mind” (Louis Pasture)


Human X-linked Recessive Human X-linked Recessive GenesGenes

Brown enamel - Tooth enamel appears brown rather than white

Hemophilia - Two types:– A - Classic hemophilia, deficiency of blood

clotting factor VIII

– B - Christmas disease, deficiency of blood clotting factor IX


X-linked Recessive GenesX-linked Recessive GenesRelated to sightRelated to sight

Coloboma iridis - A fissure in the eye’s iris Color Blindness - Two types:

– Deutan - Decreased sensitivity to green light– Protan - Decreased sensitivity to red light

Congenital night blindness - Not due to a deficency of vitimin A

Mocrophthalmia - Eyes fail to develop Optic atrophy - Degeneration of the optic nerves


Royal PedigreeRoyal Pedigree

Albert of Saxe-Coburg (18XX-18XX)

Edward Duke of Kent (1767-1820) Victoria Princess of Saxe-Coburg (1786-1861)

Emperor Frederick III of Germany (1831-1888)

Victoria (1840-1901)

Victoria Queen of England (1819-1910)

Leopold Duke of Albany(1853-1884)

Victoria(1866-1953)

King Alfonso XIII of Spain (1841-1910)

Beatrice(1857-1944)

Alice(1843-1878)

Tsar Nicholas IIof Russia (1868-1918)

Irene(1866-1953)

King Edward VII of England (1841-1910)

Alix (Alexandra)(1872-1918)

Olga(1895-1918)

Alexis(1904-1918)

Anastasia(1901-1918)

Marie(1899-1918)

Tatiana(1897-1918)


Expression of genes that are not necessarily on the X chromosome may be influenced by the gender of the individual

One major reason for this is the impact that steroid sex hormones have on the expression of genes

Male pattern baldness is the classic example of a sex influenced gene in humans

5 Sex-Influenced Or Limited Genes5 Sex-Influenced Or Limited Genes

Genotype Phenotype

Female Male

BB Bald Bald

Bb Flocculent Bald

bb Flocculent Flocculent


Genes do not work in isolation, but their expression is influenced by their environment

Just as expression of sex influenced genes are influenced by the hormones in their environment other environmental variables impact expresson of most genes

Environmental EffectsEnvironmental Effects

Being Himalayan gives a whole new meaning to the term “brown nosing.”

Documents

©2000 Timothy G. Standish Jeremiah 23:24 24Can any hide himself in secret places that I shall not see him? saith the LORD. Do not I fill heaven and earth?