PRINCIPLE OF GENETICS

10.1 HISTORICAL PERSPECTIVES

* Archeologists have discovered that as long as 7,000 years ago farmers in China
and south Asia were improving crops by planting hybrid seeds that had developed
preferred characteristics.
* Babylonian tablet shows a pedigree of a family of horses through five generations,
with detailed information about height, length of the mane, and other traits,
revealing that they had some knowledge that these traits were transmitted.
*For example, at harvest time farmers would select heads of wheat that had the
most or largest kernels and save them to use as seed the next year. For thousands
of years farmers and breeders have been selectively breeding their plants and
animals in order to produce more productive hybrids
* A number of hypotheses were suggested to explain heredity, but Gregor Mendel,
a little known Central European monk, was the only one who got it more or less
right. His ideas had been published in the 1860s but largely went unrecognized
until after his death.
* While Mendels research was with plants, the basic principles of heredity that he
discovered also apply to humans and other animals because the mechanisms of
heredity are essentially the same for all lifeforms.
*The modern science of genetics started from the rediscovery of the laws of
inheritance in 1900, which were originally postulated by Gregor Johann Mendel.
Three scientistsHugo de Vries, Tshermark, and Carl Correns rediscovered the
principles of genetics independently.
*Sutton and Boveri .They established the chromosomal basis of inheritance.
*He defined it as the science of heredity and variation.
*Bateson along with Punnet observed the variations of Mendelian inheritance and
explained the phenomenon of linkage.
*it is genetically and biochemically proven fact that a gene is a stretch of DNA that
codes for a specific polypeptide.
MENDELIAN GENETICS
*Through the selective growing of common pea plants (pisum sativum) over many
generations,
*For instance, pea flowers are either purple or white; intermediate colors do not
appear in the offspring of crosspollinated pea plants.
*Mendel observed seven traits that are easily recognized and apparently only occur
in one of two forms:
*This observation that there are traits that do not show up in offspring plants with
intermediate forms was critically important because the leading theory in biology at
the time was that inherited traits blend from generation to generation. Most of the
leading scientists in the 19th century accepted this blending theory.
*This was essentially a variation of Lamarcks incorrect idea of the inheritance of
acquired characteristics.
* Mendel picked common garden pea plants for the focus of his research because
they can be grown easily in large numbers and their reproduction can be
manipulated. Pea plants have both male and female reproductive organs. As a
result, they can either self-pollinate themselves or cross-pollinate with another
plant.
* In his experiments, Mendel was able to selectively cross-pollinate purebred plants
with particular traits and observe the outcome over many generations. This was
the basis for his conclusions about the nature of genetic inheritance.
*In cross-pollinating plants that either produce yellow or green peas exclusively,
Mendel found that the first offspring generation (f1) always has yellow peas.
However, the following generation (f2) consistently has a 3:1 ratio of yellow to
green.
*Mendel realized that this is the key to understanding the basic mechanisms of
inheritance.
*The plants in the f1 generation were all heterozygous. In other words, they each
had inherited two different allelesone from each parent plant. It becomes clearer
when we look at the actual genetic makeup, or genotype, of the pea plants instead
of only the phenotype, or observable physical characteristics.
*With all of the seven pea plant traits that Mendel examined, one form appeared
dominant over the other. Which is to say, it masked the presence of the other allele

* Mendels observations from these experiments can be summarized in three

principles: 1. Law of Dominance 2. Law of Segregation 3. Law of Independent
Assortment
* The law of dominance states that there are at least two alleles for a gene and one
of the alleles can be dominant and the other is recessive. The dominant allele, if it
is present, will always determine the trait.
For example, in pea plant tall is dominant over dwarf.
*According to the law of segregation, for any particular trait, the pair of alleles of
each parent separate and only one allele passes from each parent on to an
offspring. Which allele in a parents pair of alleles is inherited is a matter of chance.
We now know that this segregation of alleles occurs during the process of sex-cell
formation (i.e., meiosis).

*According to the law of independent assortment, different pairs of alleles are

passed to offspring independently of each other. The result is that new
combinations of genes present in either parent are possible.

Role of Chromosomes in Inheritance

* chromosomes are structures made of chromatin, which is a mixture of DNA and a
specific family of proteins called histones.
*During cell division, chromosomes are highly condensed, becoming visible by light
microscopy Some regions of the chromosome consist of chromatin that is always
highly condensed, even during interphase. These regions are called
heterochromatin (different chromatin).
*The other regions, which are uncoiled during interphase, and highly condensed
during cell division, are called euchromatin (good or true chromatin).

Sex Chromosomes
*Females have two X chromosomes in every somatic cell; males have one X and
one Y. The X and Y chromosomes are quite different, so males have two
chromosomes that do not appear as a natural pair. The Y chromosome is much
smaller than the X, and its centromere is closer to one end.
Chromosome Theory of Heredity
* Weve seen how chromosomes are segregated during cell division, but what
exactly does this have to do with the inheritance of physical traits (i.e., genes)?
Fairly soon after the rediscovery of Mendels work, many biologists believed that
genes were situated on the chromosomes, but this idea required proof.
*Evidence came in from an experiment conducted by T. H. Morgan on an eye color
mutation (white eyes) in drosophila.
*By comparing karyotypes of specific flies with their phenotype, Morgan
demonstrated that the white eye mutation was inherited along with the X
chromosome.

MULTIPLE ALLELES
*In a diploid (2n) organism every gene must exist in pairs, and each member of that
pair is called an allele or allelic pair. One of the alleles is supplied by the male
gamete (n) and the other one is given by the female gamete (n) during the process
of fertilization.
* These alleles are situated in the homologous pairs of chromosomes at specific
positions called loci.
* When there are two altered forms of a gene present in a diploid cell or in an allelic
pair, it is known as heterozygous and when the members of an allelic pair are of the
same type of genes, they are known as homozygous.
SLIDE 22 (MEANING)
For example, the gene for flower color may be present as that of red color, yellow
color, or white color. But in an individual only two of them are present in alleles, the
heterozygous allele.
SLIDE 23 (ABO BLOOD GROUP)
SLIDE 24 (MICE)
For example, hair color in mice is determined by a single gene with a series of
alleles, each resulting in different coloration. There are alleles for black, brown,
agouti, gray, albino, and others. The twist here is that the same allele can be
dominant or recessive depending on context.
(32) Allelic series are often written as agouti > black > albino. This means that
agouti is dominant to black, and black is dominant to albino. (And agouti is
necessarily also dominant to albino.)
(33) If the black allele is in the presence of an agouti allele, the mouse will be
agouti because black is recessive to agouti.
(34) If that same black allele is paired with an albino allele, the mouse will be black
since black is dominant to albino.
10.3 LINKAGE AND CROSSING OVER
(SLIDE 25 ) Linkage chromosomes.

10.4 GENETIC MAPPING

(44) Recombination can occur between any two genes on a chromosome. The
amount of crossing over is dependent on how close the genes are to each other on
the chromosome.
**If two genes are far apart, for example, at opposite ends of the chromosome,
crossover and non-crossover events will occur in equal frequency. Genes that are
closer together undergo fewer crossing over events and noncrossover gametes will
exceed the number of crossover gametes.
(45) If crossing over does not occur, the products are parental gametes.
(46) If crossing over occurs, the products are recombinant gametes.
**It is usually a simple matter to determine which gametes are recombinants.
These are the gametes that are found in the lowest frequency. This is the direct
result of the reduced recombination that occurs between two genes that are
located close to each other on the same chromosome.
Also, by looking at the gametes that are most abundant, you will be able to
determine if the original cross was a coupling or repulsion phase cross.
(47) For a coupling phase cross, the most prevalent gametes will be those with two
dominant alleles or those with two recessive alleles.
(48) For repulsion phase crosses, gametes containing one dominant and one
recessive allele will be most abundant (see Figure 10.11).
** ((50)By definition, one map unit (m.u.) is equal to one percent recombinant
phenotypes, and one m.u. is called one centimorgan (cM).
To determine the linkage distances, simply divide the number of recombinant
gametes by the total gametes produced. The frequency of recombination between
distantly placed genes and the order genes in a chromosome can be determined by
different mapping techniques. One such method is the three-point cross.
(52)There are four linkage groups in drosophila, 23 in man, 7 linkage groups in
peas, and 10 in maize. By knowing the genetic distance and the order of genes in a
chromosome it is possible to make the genetic map of that chromosome.

10.5 GENE INTERACTION OR POLYGENES

In a monohybrid cross, the F2 generation will show two phenotypes in the ratio 3:1
known as the monohybrid ratio. This happens only when there is complete
dominance.
In dihybrid crosses the F2 generation will have four phenotypes in the ratio 9:3:3:1.
This is applicable when genes are independent (absence of linkage) and show
complete dominance.
In the case of incomplete dominance the heterozygous ratio of a monohybrid cross
will modify into 1:2:1, which is actually the genotypic ratio.
Phenotypic characteristics such as high blood pressure (hypertension) are not the
result of a single blood pressure gene with many alleles (a 120/80 allele, a 100/70
allele, a 170/95 allele, etc.). This phenotype is the result of interactions between a
persons weight (one or more obesity genes), cholesterol level (one or more genes
controlling metabolism), kidney function (salt transporter genes), smoking (a
tendency to addiction), and probably lots of others, too.
Similarly, eye color in man is due to complex interactions of two genes each having
pairs of incompletely dominant alleles. Skin color is determined by the interactions
between at least three independent genes having two or more alleles.

10.6 SEX-LINKED INHERITANCE

Those chromosomes, which are responsible for the determination of the sex of an
organism, are termed as sex chromosomes or X chromosomes. All other
chromosomes of the cell are autosomes.
There are two types of sex chromosomes: X chromosomes and Y chromosomes. X
chromosomes in homozygous conditions determine femaleness and association of X
chromosomes and Y chromosomes produce maleness. We designate the male XY
and the female XX.
The X chromosome contains a significant number of genes. In contrast, the Y
chromosome contains very few. Therefore, genes on the X chromosome (often
called X-linked genes) are in a unique situation.
Females have two copies of each gene, just like the normal situation, with
autosomal (in humans, there are 22 pairs of autosomes) genes.
Males, on the other hand, since they have only one Xchromosome, have only one
copy of each X-linked gene. Because of this, males cannot be homozygous or
heterozygous; they are referred to as hemizygous (The condition of having only one
allele of a pair.)
Therefore, alleles that are recessive in a female are automatically expressed in a
male (because there is no second allele to overshadow the recessive one). The
normal rules of dominance do not apply to males in this case. For this reason,
problems associated with X-linked recessive alleles, such as hemophilia (inability of
blood to clot) and color blindness are more common in males than they are in
females.

Lets consider hemophilia as an example. For a female to be affected by

hemophilia, she has to be homozygous for the hemophilia allele (which we will
designate h). If an affected female mates with an unaffected male:
All of the male offspring would be affected by hemophilia. All of the female offspring
would be unaffected, but would be carriers. This criss-cross pattern of inheritance of
a phenotype (from mother to sons) is one of the features of X-linked inheritance. If
the female parent is a carrier, and the male parent is a hemophiliac, the following
offspring are obtained:
Half of the offspring of each gender will, on an average, be hemophiliac. The origin
of the hemophilia that plagued the crowned families of Europe is actually of
English/German origin.
Queen Victoria was the original carrier. Her son the Prince of Wales did not inherit it,
and so the British royal family has been free of the disease. The royal families of
France, Spain, and Russia, whose daughters were carriers of the hemophilia gene
were not so lucky.
Sex-influenced traits are related to sex but not coded by genes on the sex
chromosomes (baldness, gout, allergies, and cleft palate are all generally more
prevalent in men than women). Typically, they are influenced by the hormone,
testosterone (in both men and women).
Chromosomal non-disjunction is the improper segregation of chromosomes during
cell division. Often, it occurs in sex chromosomes of males or females but it may
occur in an autogenous model as well.

10.7 EXTRA NUCLEAR INHERITANCE

According to traditional ideas the genome is located in the nucleus of a
eukaryotic cell. But there are some genes present in the cytoplasm, inside the
organelles, such as mitochondria and chloroplasts. These organelles have a circular
DNA molecule similar to that of a eukaryotic system. The characteristics inherited
by them are known as extra chromosomal inheritance or cytoplasmic inheritance.

During fertilization only the nucleus of the male gamete enters the egg, leaving the
cytoplasm outside. Thus, the cytoplasm or the cytoplasmic genes of the zygote are
contributed only by the egg and not by the male gamete. Therefore, the extra
chromosomal inheritance is also known as maternal inheritance.
There are three types of cytoplasmic inheritance known today:
A. Maternal influence (egg cytoplasm influences the phenotype of the offspring)
B. Organelle heredity (mitochondria and chloroplasts)
C. Infectious heredity (an infectious particle is transmitted during conjugation)

Cytoplasmic inheritance shows certain special features. (1) Lack of Mendelian

segregation and typical Mendelian ratios. (2) Persistence of characteristics for many
generations. (3) Controlled by mitochondrial and chloroplast DNA. (4) Shows
maternal inheritance as these characters are transmitted only by female gametes.

Variegation in Four oclock Plant and Maternal Inheritance

The classic study of maternal inheritance was performed by Carl Correns on the
four oclock plant. This plant can have green, variegated (white and green), or white
leaves. Flower structures can develop at different locations on the plant and the
flower color corresponds to the leaf color.
When Correns crossed the different colored flowers from different locations on the
female plant with pollen obtained from flowers of the three different colors, the
progeny that resulted from the cross always exhibited the color of the leaf of the
female. That is, regardless of whether the pollen was from a leaf that was green,
variegated, or white.
In the case of the four oclock plant, the different colors of the leaves are a result of
the presence or absence of chlorophyll in the chloroplast, a trait that can be
controlled by the chloroplast DNA.
Thus, green shoots contain chloroplasts that have chlorophyll, the chloroplasts in
the white shoots contain no chlorophyll, and the variegated shoots contain some
chloroplasts with chlorophyll and some without chlorophyll. Thus, depending on the
location in the plant where the flower comes from, the egg can have chloroplast
with chlorophyll, without chlorophyll, or a mixture of the two types of chloroplasts.
This is the biological basis of maternal inheritance.
Snail Shell Coiling and Maternal Effects
The embryo is formed when a female gamete unites with a male gamete. In the
vast majority of species, the female gamete is physically larger than the male
gamete and provides the cytoplasm for the developing embryo.
Those phenotypes that are controlled by nuclear factors found in the cytoplasm of
the female are said to express a maternal effect. Those phenotypes controlled by
organelle genes exhibit maternal inheritance.
The classic phenotype, which exhibits maternal effects, is the coiling direction of
snail shells. The coiling phenotype that is seen in the offspring is controlled by the
genotype of the mother.

**Petite Mutations in Saccharomyces Cerevisiae

Yeast cells usually form large colonies called grande on nutrient agar plates. Rarely
small or minute colonies known as petite also appear among them.
Petite yeasts produce small colonies because they are unable to carry out aerobic
respiration as they have defective mitochondria (with defective electron transport
proteins; cytochromes a, b, and c).

There are three types of petite mutants that differ in their mode of inheritance.
The inheritance of a nuclear gene of haploid yeast shows Mendelian segregation of
asosopres into a 2:2 ratio. Such a ratio is found when the first category of petite
mutants is crossed with the grande wild type and thus a nuclear gene controls this
phenotype, the segregational petites.
In the second type the cross between the grande and petite phenotypes results in
progeny with all normal phenotypes known as neutral petites.
In the third category the cross between grande and petite phenotypes produces all
petite progeny, and they are known as suppressive petites. (Figure 10.16). The
inheritance of poky phenotype (similar to petite yeasts) in Neurospora crassa and
cytoplasmic male sterility in maize are also governed by the mitochondrial gene.
Cytoplasmic male sterility (CMS), a cytoplasmic mutation, is extremely important
for agriculture. CMS plants are male-sterile and female-fertile. These mutations are
in the mitochondria and are maternally inherited.
The complete nucleotide sequence of human mitochondrial DNA has been
determined (16,569 nucleotides). 1. Human mitochondrial DNA codes for 13
proteins, 22 tRNAs, and 2 rRNAs. 2. The complete nucleotide sequences have been
determined for mitochondria and chloroplasts of many other organisms. 3.
Mitochondria have hundreds of proteins, but only a small number (13 in humans)
are coded for by the mitochondrial genome. 4. Most proteins in mitochondria are
coded for by the nuclear genome, translated on cytoplasmic ribosomes, and
imported into the mitochondria. (Figure 10.17).
An endosymbiont is a symbiont that is present inside a cell. Anaerobic
prokaryotes were thought to be the first living things on earth. Anaerobic
prokaryotes evolved into aerobic prokaryotes.
The oxygen released by aerobic prokaryotes was toxic to the anaerobic
prokaryotes, and this presumably was the driving force that caused anaerobic
prokaryotes to evolve into aerobic prokaryotes.
Anaerobic prokaryotes evolved into anaerobic eukaryotes. The anaerobic
eukaryotes took up aerobic prokaryotes as an endosymbiont, and the aerobic
prokaryotes became mitochondria.

10.8 QUANTITATIVE INHERITANCE

Many genes control the inheritances of certain single traits that are measured in a
quantitative manner.
Some of the examples for quantitative inheritance include: A. Height B. Weight C.
Yield in crops D. Growth rate in farm animals E. IQ, etc.
In addition to quantitative inheritance, inheritance of these traits is often referred to
as cumulative gene action or polygenic-inheritance.
Genetic analysis of contributing genes can best be examined using simplified
models.
As an example, lets consider plant height in grain sorghum (often called milo). Wild
sorghums brought from Africa are often 10' tall; those grown from grain are nearly
2' tall, which greatly simplifies harvest. The combine types are sometimes
referred to as 4-dwarf sorghums.

The model for sorghum height is as follows: There are four genes involved in height
determination. Each gene has two alleles, one of which adds about one foot of
height; the other is null.
The alleles that contribute to height are called contributing alleles, and are
designated by primes, A, B, C, etc. Non-contributing (null) alleles are designated
with A, B, C etc. (Sometimes a, b, c may be used.)
A plant with no contributing alleles is 2 tall (AA, BB, CC, DD). Each gene is
equivalent and shows incomplete dominance; that is, AA adds 2 feet, AA adds 1
foot, and AA adds 0 feet to the base height. The same is true for the B, C, and D
gene loci. A plant with the genotypes AA, BB, CC, DD, or AA, BB CC, DD will be 4
tall.

If we allow the 3 tall F1 progeny to self pollinate, which is normal in sorghum, we

expect to see a 1:2:1 ratio of F2 plants that are 4:3:2 tall, respectively.
This is true because only one gene with incomplete dominance is segregating
(heterozygous) in the F1 hybrid. (AA X AA gives 1/4th AA: 2/4th AA:1/4th AA). The
same would be true if AA, BB, CC, DD, or any other 4 tall true breeding plant
(homozygous at all 4 gene loci) was crossed to the AA, BB, CC, DD parent. What if
we cross AA BB, CC, DD to AA, BB, CC, DD? Both parents are 4 tall as is the F1,
but the F1 is heterozygous for 2 genes (AA, BB, CC, DD). Now in the F2, we can
predict that, 1/4th of the progeny will be AA and that 1/4th of these will also be BB
; thus, 1/16th of the progeny should be 6' tall! Likewise, 1/16th should be AA, BB,
CC, DD, or only 2' tall having no primes.
When the range in the F2 progeny goes beyond the original parents, we see
transgressive segregation.
Transgressive segregation implies that the parents donate contributing alleles from
different genes to the hybrid. There should also be plants in the F2 generation that
have one contributing allele (AA, BB, CC, DD, or AA, BB, CC, DD). These should
represent 1/4th (1/8th + 1/8th) of the progeny, and they will be 3' tall.
The same is true for plants with three contributing alleles (AA, BB, CC, DD, and A
A, BB, CC, DD).
Genes that contribute to quantitative traits are referred to as polygenes, or QTLs,
which stands for quantitative trait loci.
When this model applies, the hybrid will always show a phenotype that is the
average of the parents, and there will be more variation among the F2 progeny
than in either P1 or F1 progeny. It would not be difficult to imagine cases where
some genes made larger or smaller contributions than others, or where one or more
genes may be dominant.
Environmental Effects
Most or all quantitative traits are also influenced by environmental factors. In the
case of sorghum height, plants will not reach their genetic potential without water,
nutrients (fertilizer), and sunlight.
Environmental effects means that some differences can be seen within a purebred
parent or in an F1 population, where all of the plants have the same exact
genotype. Environmental effects will also smooth out the stair-step effect
expected for genotypes in the F2 that differ in the number of contributing alleles.
Since it is not possible to count the number of classes in an F2 population when
environmental effects smooth away the genotypic differences, or to identify
individuals in the extremes, the number of genes that contribute to the trait cannot
be simply estimated.
Normal statistical methods can be used for studying the inheritance of quantitative
traits and to analyze the contributions of genes and environment to a trait. The
concept is to partition the sources of variation that lead to differences among
individuals in the sample, and to identify the portion of variation that results from
segregating genes. Total variation (Vt), which is often called phenotypic variation
(Vp), arises from differences in genotype (Vg), the environment (Ve), and may also
result from interactions (Vgxe) where some genotypes do better in one
environment and others in another.
Vt = Vp = (Vg + Ve + Vgxe)
In many cases, the interaction component cannot be measured, so it is ignored or
handled by working within a specific environment or only working with a specific
breed or cross.

Heritability (H2 or broad-sense heritability) is the fraction of variation due to genetic

differences (i.e., Vg. H2 = Vg/Vt). It is relatively simple to make H2 estimates in
plants, since pure-breeding completely homozygous parents can be maintained.
Any variation within a pure-breeding homozygous parent, or in the F1 progeny of a
cross between two pure-breeding parents must result from Ve, since all plants
within each of the populations have the exact same genotype. Thus, these plants
can be used to estimate Ve (variation) among F2 plants, which arises both from
differences in genotype and from local environments. So the variation in the F2 is a
measure of Vt. In the example below, two true breeding corn parents, one with an
average row number of six, is crossed to another with an average of fourteen rows.
The F1, as expected, is right between the parents, having an average of ten rows.
Variance (V) for row number in the parents and F1 is low (arbitrarily measured as 1)
Variance in the F2 is eight. Vt(8) = Vg + Ve (1); ignoring Vgxe since all plants were
grown in the same environment, Vg must be 7. Therefore, H2 = 7/8. It is critical to
realize that: 1. Heritability measures are only valid for the population that was
measured. 2. Genetic differences will not be measured unless the parents have
different alleles. 3. In the environment, gene interactions may be important, but are
generally ignored. Plant and animal breeders are interested in heritability, because
it allows them to predict if selective breeding can be used to improve a trait. For
example, if rate of weight gain in nursing Hampshire pigs is highly heritable, saving
those that grow the fastest for breeding purposes will lead to improved weight gain
in future generations. If H2 is low, changes in the diet may be more important.
Selection will make progress as long as genetic differences can be combined to
make an improved genotype. Selection for one trait may be balanced by loss in
another; for example, selection for increased egg size in leghorns is successful, but
the hens lay fewer eggs.