CHAPTER
14
MENDEL AND THE GENE IDEA
·
Every
day we observe heritable variations (eyes of brown, green, blue, or gray) among
individuals in a population.
·
These
traits are transmitted from parents to offspring.
·
One
mechanism for this transmission is the “blending” hypothesis.
·
This
hypothesis proposes that the genetic material contributed by each parent mixes
in a manner analogous to the way blue and yellow paints blend to make green.
·
Over
many generations, a freely mating population should give rise to a uniform
population of individuals.
·
However,
the “blending” hypothesis appears incorrect as everyday observations and the
results of breeding experiments contradict its predictions.
·
An
alternative model, “particulate” inheritance, proposes that parents pass on
discrete heritable units - genes - that retain their separate identities in
offspring.
·
Genes
can be sorted and passed on, generation after generation, in undiluted form.
· Modern genetics began in an abbey garden, where a monk names Gregor Mendel documented the particulate mechanism of inheritance.
1. Mendel brought an experimental and quantitative
approach to genetics
·
Mendel
grew up on a small farm in what is today the Czech Republic.
·
In
1843, Mendel entered an Augustinian monastery.
·
He
studied at the University of Vienna from 1851 to 1853 where he was influenced
by a physicist who encouraged experimentation and the application of
mathematics to science and by a botanist who aroused Mendel’s interest in the
causes of variation in plants.
·
These
influences came together in Mendel’s experiments.
·
After
the university, Mendel taught at the Brunn Modern School and lived in the local
monastery.
·
The
monks at this monastery had a long tradition of interest in the breeding of
plants, including peas.
·
Around
1857, Mendel began breeding garden peas to study inheritance.
·
Pea
plants have several advantages for genetics.
·
Pea
plants are available in many varieties with distinct heritable features (characters) with different variants (traits).
·
Another
advantage of peas is that Mendel had strict control over which plants mated
with which.
·
Each
pea plant has male (stamens) and female (carpal) sexual organs.
·
In
nature, pea plants typically self-fertilize, fertilizing ova with their own
sperm.
·
However,
Mendel could also move pollen from one plant to another to cross-pollinate
plants.
·
In
a typical breeding experiment, Mendel would cross-pollinate (hybridize) two contrasting, true-breeding pea varieties.
·
The
true-breeding parents are the P
generation and their hybrid offspring are the F1 generation.
·
Mendel
would then allow the F1 hybrids to self-pollinate to produce an F2
generation.
·
It
was mainly Mendel’s quantitative analysis of F2 plants that revealed
the two fundamental principles of heredity: the law of segregation and the law
of independent assortment.
2. By the law of segregation, the two alleles for a
character are packaged into separate gametes
·
If
the blending model were correct, the F1 hybrids from a cross between
purple-flowered and white-flowered pea plants would have pale purple flowers.
·
Instead,
the F1 hybrids all have purple flowers, just as purple as the
purple-flowered parents.
·
When
Mendel allowed the F1 plants to self-fertilize, the F2
generation included both purple-flowered and white-flowered plants.
·
The
white trait, absent in the F1, reappeared in the F2.
·
Based
on a large sample size, Mendel recorded 705 purple-flowered F2
plants and 224 white-flowered F2 plants from the original cross.
·
This
cross produced a three purple to one white ratio of traits in the F2
offspring.
·
Mendel
reasoned that the heritable factor for white flowers was present in the F1
plants, but it did not affect flower color.
·
Purple
flower is a dominant trait and white flower is a recessive trait.
·
The
reappearance of white-flowered plants in the F2 generation indicated
that the heritable factor for the white trait was not diluted or “blended” by
coexisting with the purple-flower factor in F1 hybrids.
·
Mendel
found similar 3 to 1 ratios of two traits among F2 offspring when he
conducted crosses for six other characters, each represented by two different
varieties.
·
For
example, when Mendel crossed two true-breeding varieties, one of which produced
round seeds, the other of which produced wrinkled seeds, all the F1 offspring
had round seeds, but among the F2 plants, 75% of the seeds were
round and 25% were wrinkled.
·
Mendel
developed a hypothesis to explain these results that consisted of four related
ideas.
• 1)
Alternative version of genes (different alleles) account for variations in
inherited characters.
·
Different
alleles vary somewhat in the sequence of nucleotides at the specific locus of a
gene.
·
The
purple-flower allele and white-flower allele are two DNA variations at the
flower-color locus.
• 2) For each character, an organism inherits two alleles, one from each parent.
·
A
diploid organism inherits one set of chromosomes from each parent.
·
Each
diploid organism has a pair of homologous chromosomes and therefore two copies
of each locus.
·
These
homologous loci may be identical, as in the true-breeding plants of the P
generation.
·
Alternatively,
the two alleles may differ
·
In
the flower-color example, the F1 plants inherited a purple-flower
allele from one parent and a white-flower allele from the other.
• 3) If two alleles differ, then one, the dominant allele, is fully expressed in the organism’s appearance.
• The
other, the recessive allele, has no
noticeable effect on the organism’s appearance.
·
Mendel’s
F1 plants had purple flowers because the purple-flower allele is
dominant and the white-flower allele is recessive.
• 4) The two alleles for each character segregate (separate) during
gamete production.
·
This
segregation of alleles corresponds to the distribution of homologous
chromosomes to different gametes in meiosis.
·
If
an organism has identical allele for a particular character, then that allele
exists as a single copy in all gametes.
·
If
different alleles are present, then 50% of the gametes will receive one allele
and 50% will receive the other.
·
The
separation of alleles into separate gametes is summarized as Mendel’s law of segregation.
·
Mendel’s
law of segregation accounts for the 3:1 ratio that he observed in the F2
generation.
·
The
F1 hybrids will produce two classes of gametes, half with the
purple-flower allele and half with the white-flower allele.
·
During
self-pollination, the gametes of these two classes unite randomly.
·
This
can produce four equally likely combinations of sperm and ovum.
·
A
Punnett square predicts the results
of a genetic cross between individuals of known genotype.
·
A
Punnett square analysis of the flower-color example demonstrates Mendel’s
model.
·
One
in four F2 offspring will inherit two white-flower alleles and
produce white flowers.
·
Half
of the F2 offspring will inherit one white-flower allele and one
purple-flower allele and produce purple flowers.
·
One
in four F2 offspring will inherit two purple-flower alleles and
produce purple flowers too.
·
Mendel’s
model accounts for the 3:1 ratio in the F2 generation.
·
An
organism with two identical alleles for a character is homozygous for that character.
·
Organisms
with two different alleles for a character is heterozygous for that character.
·
A
description of an organism’s traits is its phenotype.
·
A
description of its genetic makeup is its genotype.
·
Two
organisms can have the same phenotype but have different genotypes if one is homozygous
dominant and the other is heterozygous.
·
For
flower color in peas, both PP and Pp plants have the same phenotype
(purple) but different genotypes (homozygous and heterozygous).
·
The
only way to produce a white phenotype is to be homozygous recessive (pp) for the flower-color gene.
·
It
is not possible to predict the genotype of an organism with a dominant
phenotype.
·
The
organism must have one dominant allele, but it could be homozygous dominant or
heterozygous.
·
A
testcross, breeding a homozygous
recessive with dominant phenotype, but unknown genotype, can determine the
identity of the unknown allele.
3. By the
law of independent assortment, each pair of alleles segregates into gametes
independently
·
Mendel’s
experiments that followed the inheritance of flower color or other characters
focused on only a single character via monohybrid
crosses.
·
He
conducted other experiments in which he followed the inheritance of two
different characters, a dihybrid
cross.
·
In
one dihybrid cross experiment, Mendel studied the inheritance of seed color and
seed shape.
·
The
allele for yellow seeds (Y) is
dominant to the allele for green seeds (y).
·
The
allele for round seeds (R) is
dominant to the allele for wrinkled seeds (r).
·
Mendel
crossed true-breeding plants that had yellow, round seeds (YYRR) with true-breeding plants that has green, wrinkled seeds (yyrr).
·
The
two pairs of alleles segregate independently of each other.
·
The
presence of one specific allele for one trait has no impact on the presence of
a specific allele for the second trait.
·
In
our example, the F1 offspring would still produce yellow, round
seeds.
·
However,
when the F1’s produced gametes, genes would be packaged into gametes
with all possible allelic combinations.
·
Four
classes of gametes (YR, Yr, yR,
and yr) would be produced in equal
amounts.
·
When
sperm with four classes of alleles and ova with four classes of alleles
combined, there would be 16 equally probable ways in which the alleles can
combine in the F2 generation.
·
These
combinations produce four distinct phenotypes in a 9:3:3:1 ratio.
·
This
was consistent with Mendel’s results.
·
Mendel
repeated the dihybrid cross experiment for other pairs of characters and always
observed a 9:3:3:1 phenotypic ration in the F2 generation.
·
Each
character appeared to be inherited independently.
·
The
independent assortment of each pair of alleles during gamete formation is now
called Mendel’s law of independent
assortment.
·
One
other aspect that you can notice in the dihybrid cross experiment is that if
you follow just one character, you will observe a 3:1 F2 ratio for
each, just as if this were a monohybrid cross.
4. Mendelian inheritance reflects rules of probability
·
Mendel’s
laws of segregation and independent assortment reflect the same laws of
probability that apply to tossing coins or rolling dice.
·
The
probability scale ranged from zero (an event with no chance of occurring) to
one (an event that is certain to occur).
·
The
probability of tossing heads with a normal coin is 1/2.
·
The
probability of rolling a 3 with a six-sided die is 1/6, and the probability of
rolling any other number is 1 - 1/6 = 5/6.
·
When
tossing a coin, the outcome of one toss has no impact on the outcome of the
next toss.
·
Each
toss is an independent event, just like the distribution of alleles into
gametes.
·
Like
a coin toss, each ovum from a heterozygous parent has a 1/2 chance of carrying
the dominant allele and a 1/2 chance of carrying the recessive allele.
·
The
same odds apply to the sperm.
·
We
can use the rule of multiplication to determine the chance that two or more
independent events will occur together in some specific combination.
·
Compute
the probability of each independent event.
·
Then,
multiply the individual probabilities to obtain the overall probability of
these events occurring together.
·
The
probability that two coins tossed at the same time will land heads up is 1/2 x
1/2 = 1/4.
·
Similarly,
the probability that a heterogyzous pea plant (Pp) will produce a white-flowered offspring (pp) depends on an ovum with a white allele mating with a sperm with
a white allele.
·
This
probability is 1/2 x 1/2 = 1/4.
·
The
rule of multiplication also applies to dihybrid crosses.
·
For
a heterozygous parent (YyRr) the
probability of producing a YR gamete
is 1/2 x 1/2 = 1/4.
·
We
can use this to predict the probability of a particular F2 genotype
without constructing a 16-part Punnett square.
·
The
probability that an F2 plant will have a YYRR genotype from a heterozygous parent is 1/16 (1/4 chance for a YR ovum and 1/4 chance for a YR sperm).
·
The
rule of addition also applies to genetic problems.
·
Under
the rule of addition, the probability of an event that can occur two or more
different ways is the sum of the separate probabilities of those ways.
·
For
example, there are two ways that F1 gametes can combine to form a
heterozygote.
·
The
dominant allele could come from the sperm and the recessive from the ovum
(probability = 1/4).
·
Or,
the dominant allele could come from the ovum and the recessive from the sperm
(probability = 1/4).
·
The
probability of a heterozygote is 1/4 + 1/4 = 1/2.
5. Mendel discovered the particulate behavior of
genes: a review
·
While
we cannot predict with certainty the genotype or phenotype of any particular
seed from the F2 generation of a dihybrid cross, we can predict the
probabilities that it will fit a specific genotype of phenotype.
·
Mendel’s
experiments succeeded because he counted so many offspring and was able to
discern this statistical feature of inheritance and had a keen sense of the
rules of chance.
·
Mendel’s
laws of independent assortment and segregation explain heritable variation in
terms of alternative forms of genes that are passed along according to simple
rule of probability.
·
These
laws apply not just to garden peas, but to all other diploid organisms that
reproduce by sexual reproduction.
· Mendel’s studies of pea inheritance endure not only in genetics, but as a case study of the power of scientific reasoning using the hypothetico-deductive approach.
B. Extending Mendelian Genetics
1. The relationship between genotype and phenotype
is rarely simple
·
In
the 20th century, geneticists have extended Mendelian principles not only to
diverse organisms, but also to patterns of inheritance more complex than Mendel
described.
·
In
fact, Mendel had the good fortune to choose a system that was relatively simple
genetically.
·
Each
character (but one) is controlled by a single gene.
·
Each
gene has only two alleles, one of which is completely dominant to the other.
·
The
heterozygous F1 offspring of Mendel’s crosses always looked like one
of the parental varieties because one allele was dominant to the other.
·
However,
some alleles show incomplete dominance where
heterozygotes show a distinct intermediate phenotype, not seen in homozygotes.
·
This
is not blended inheritance because the traits are separable (particulate) as
seen in further crosses.
·
Offspring
of a cross between heterozygotes will show three phenotypes: both parentals and
the heterozygote.
·
The
phenotypic and genotypic ratios are identical, 1:2:1.
·
A
clear example of incomplete dominance is seen in flower color of snapdragons.
·
A
cross between a white-flowered plant and a red-flowered plant will produce all
pink F1 offspring.
·
Self-pollination
of the F1 offspring produces 25% white, 25% red, and 50% pink
offspring.
·
Incomplete
and complete dominance are part of a spectrum of relationships among alleles.
·
At
the other extreme from complete dominance is codominance in which two alleles affect the phenotype in separate,
distinguishable ways.
·
For
example, the M, N, and MN blood groups of humans are due to the presence of two
specific molecules on the surface of red blood cells.
·
People
of group M (genotype MM) have one type of molecule on their red blood cells,
people of group N (genotype NN) have the other type, and people of group MN
(genotype MN) have both molecules present.
·
The
dominance/recessiveness relationships depend on the level at which we examine
the phenotype.
·
For
example, humans with Tay-Sachs disease lack a functioning enzyme to metabolize
gangliosides (a lipid) which accumulate in the brain, harming brain cells, and
ultimately leading to death.
·
Children
with two Tay-Sachs alleles have the disease.
·
Heterozygotes
with one working allele and homozygotes with two working alleles are “normal”
at the organismal level, but
heterozygotes produce less functional enzymes.
·
However,
both the Tay-Sachs and functional alleles produce equal numbers of enzyme
molecules, codominant at the molecular level.
·
Because
an allele is dominant does not necessarily mean that it is more common in a
population than the recessive allele.
·
For
example, polydactyly, in which individuals are born with extra fingers or toes,
is due to an allele dominant to the recessive allele for five digits per
appendage.
·
However,
the recessive allele is far more prevalent than the dominant allele in the
population.
·
399
individuals out of 400 have five digits per appendage.
·
Dominance/recessiveness
relationships have three important points.
• 1) They range from complete dominance, though various degrees of incomplete dominance, to codominance.
• 2) They reflect the mechanisms
by which specific alleles are expressed in the phenotype and do not involve the
ability of one allele to subdue another at the level of DNA.
• 3) They do not determine or
correlate with the relative abundance of alleles in a population.
·
Most
genes have more than two alleles in a population.
·
The
ABO blood groups in humans are determined by three alleles, IA, IB, and i.
·
Both
the IA and IB alleles are dominant to
the i allele
·
The
IA and IB alleles are codominant to
each other.
·
Because
each individual carries two alleles, there are six possible genotypes and four
possible blood types.
·
Individuals
that are IA IA
or IA i are type A and place
type A oligosaccharides on the surface of their red blood cells.
·
Individuals
that are IB IB
or IB i are type B and
place type B oligosaccharides on the surface of their red blood cells.
·
Individuals
that are IA IB
are type AB and place both type A and type B oligosaccharides on the surface of
their red blood cells.