INHERITANCE

GAMETES AND REPRODUCTION

 Sexual reproduction involves the production of special sex cells, called gametes. The
nuclei of two gametes fuse together, in a process called fertilisation. The cell produced by
this fusion is called a zygote. The zygote then divides repeatedly by mitosis, producing a
multicelled organism.
 Each chromosome contains a DNA molecule, which in turn contains the code for the
synthesis of many different polypeptides or proteins. A length of DNA coding for one
protein or polypeptide is called a gene.
 When a cell divides, it is important that each new (daughter) cell obtains a complete set
of genes. During sexual reproduction, however, something a little different is required.

HAPLOID AND DIPLOID CELLS

 In most of your body cells there are two complete sets of chromosomes in the nucleus. A
cell that has two complete sets of chromosomes is said to be diploid.
 One complete set of chromosomes contains one complete set of genes and therefore one
complete set of instructions for making all the proteins that the organism needs. In
humans, there are 23 chromosomes in one complete set. There are therefore 46
chromosomes in a diploid cell.
 Each chromosome has a number. The chromosomes with the same number contain the
same genes in the same positions. These are said to be homologous chromosomes.
 During sexual reproduction, each gamete contributes one set of chromosomes to form
the zygote. It is therefore important that
gametes have only one set of chromosomes.
A cell with a single set of chromosomes is
said to be haploid.
 You can use the letter n to signify the
number of chromosomes in one set. A
haploid cell has n number of chromosomes,
and a diploid cell has 2n.
 Gametes need to be haploid so that, when
their nuclei fuse, a zygote is formed with the
diploid number of chromosomes.
MEIOSIS

 Meiosis is a type of nuclear division that produces haploid cells from a diploid cell. It is
used in the production of gametes in animals and plants.
 Meiosis has two divisions, not one as in mitosis. These are called meiosis I and meiosis II.
Each division has the same sequence of stages as in mitosis – prophase, metaphase,
anaphase and telophase.
THE PRODUCTION OF GENETIC VARIATION
 The position of a gene on a chromosome is called its locus (plural: loci) You may
remember that genes can exist in different forms, called alleles.
 So, in a diploid cell, each member of a pair of homologous chromosomes may contain
different alleles of the same gene. The two homologous chromosomes are not genetically
identical.
 Two processes that happen during meiosis I result in a mixture of these alleles that is not
the same in every daughter cell. These processes are crossing over and independent
assortment.

GENETIC VARIATION ARISING FROM CROSSING OVER

 In some of the cells undergoing meiosis, crossing

over between these two gene loci does not
happen. The alleles stay on their own
chromosome. But in some of the cells, crossing
over switches the positions of the alleles. Now the
alleles on one chromosome are E and a, and on the
other they are e and A.
 At the end of meiosis, when the new daughter
cells (gametes) are finally formed, each one
gets just one chromatid from each
chromosome. Some will get the non-crossed-
over chromatids, so will have either E and A
or e and a. But some will get crossed-over
chromatids, and they will have either E and a
or e and A. This means that there are four
different kinds of gamete

GENETIC VARIATION ARISING FROM INDEPENDENT ASSORTMENT

 As the homologous chromosomes are pulled

apart, the combination of alleles that ends up in
the daughter cells depends on how these
chromosomes were lined up. Looking at just two
pairs of chromosomes, each with one gene, you
can see that four different combinations of alleles
are possible.
 Now imagine how many combinations of alleles
you can get with 23 pairs of chromosomes, each
with hundreds or thousands of genes on them. It
would seem to be almost limitless. The ability of
 any allele to find itself in the same cell as any other allele is called independent
assortment.

GENETIC VARIATION ARISING FROM RANDOM FERTILISATION

 If you assume that any male gamete can fuse with any female gamete, each with these
potentially large amounts of variation between them, you can see that the new
individuals produced as a result of sexual reproduction have almost no chance of being
genetically identical. They will inevitably have different combinations of alleles.

GENETICS
 Genetics is the study of how characteristics that are determined by genes are passed
down from a parent or parents to their offspring.
 You will remember that a gene is a length of DNA that codes for the production of a
polypeptide molecule. The code is held in the sequence of nucleotide bases in the DNA. A
triplet of three bases codes for one amino acid in the polypeptide that will be constructed
on the ribosomes in the cell. One chromosome contains enough DNA to code for many
polypeptides.


For codominant alleles

MONOHYBRID INHERITANCE AND GENETIC DIAGRAMS
 Always show the complete genetic diagram, including the headings at the left-hand side.
This makes clear to someone looking at your work exactly what you are showing – and it
also helps you to remember what you are doing.
 The grid that is drawn part way through the genetic diagram is called a Punnett square.
A Punnett square is not a genetic diagram! It is a part of a genetic diagram.
 In the parental gametes line you are showing the different types of gamete that each
parent can produce. If the parent is homozygous, as for the white parent in the first
genetic diagram, there is only one type of gamete that can be produced. So you need only
show this one type. There is no need to write down b and b . If you do that, you will still
get the right answer at the end, but your diagram will be unnecessarily complicated.
 You will usually be expected to show which phenotype is associated with which
genotype, in the offspring. The easiest way to do this is to write the phenotype just
underneath the genotype in the Punnett square.
 It is important to remember that the predicted genotypes are all based on chance. You
cannot be sure which sperm will fertilise which egg. In the cross between the two
heterozygous rabbits above, the prediction is that there will be three times as many
brown offspring as white offspring. However, you should not be surprised if this does not
work out exactly. For example, if only two baby rabbits are born, they could both be
brown. They could even both be white.
 Genetic diagrams involving codominant alleles are constructed in exactly the same way
as in the example above, but of course using the correct symbols for these alleles.
F1
AND F2 TEST CROSSES

 If two homozygous individuals are crossed – for example, a homozygous brown rabbit,
BB, with a homozygous white rabbit, bb – the offspring are known as the F1 generation.
They are, of course, always all heterozygous.
 If two of the F1 generation are crossed, their offspring are known as the F2 generation.
 You will probably have noticed by now that, if an individual shows the recessive
phenotype, it must be homozygous for the recessive allele. A white rabbit always has the
genotype bb. However, the genotype of a brown rabbit is unknown. It could be Bb, or it
could be BB.
 In order to determine the genotype of an individual showing the dominant characteristic
in its phenotype, you can do a test cross. This involves crossing the unknown individual
with one showing the recessive phenotype. By looking at the phenotypes of the offspring,
you can obtain information about the genotype of the parent.

SEX LINKAGE

 In men, one of these sex chromosomes is a short chromosome with very few genes on it,
called the Y chromosome. The other is much longer, and contains many genes that are
not found on the Y chromosome. This is called the X chromosome. Men have one of each
of these chromosome (XY) while women have two X chromosomes (XX).
 One of the genes on the X chromosome codes for the production of a factor necessary for
blood clotting, called factor VIII. There are two alleles, a dominant one that codes for the
 normal factor VIII, and a recessive one which results in the lack of factor VIII. You can use
the symbols F and f for these two alleles. A person with only this recessive allele, and no
dominant allele, does not make factor VIII. Their blood does not clot normally, and they
have haemophilia.
 This gene is said to be sex-linked. Because it is found only on the X chromosome, its
inheritance is affected by the sex of an individual

DIHYBRID INHERITANCE
 This is an example of a dihybrid test cross. If you cross an individual showing the
dominant characteristics in their phenotype with one showing the recessive
characteristics, you can use the phenotypes of the offspring to work out the genotype of
the unknown parent.

 The expected
phenotype ratios are
therefore 9 purple stem,
cut leaves:3 purple
stem, potato leaves:3
green stem, cut leaves:1
green stem, potato
leaves.
 This 9 :3:3:1 ratio is
typical of a dihybrid
cross where both
parents are
heterozygous at both
gene loci.
EPISTASIS

 Sometimes, two different genes on different chromosomes affect the same feature. The
alleles of one gene affect the expression of the other. This is called epistasis.
 For example, in the inheritance of feather
colour in chickens, there is an interaction
between two gene loci on different
chromosomes, F/f and G/g. The gene G/g
determines whether or not the bird produces
coloured feathers – allele G codes for a
pigment that produces coloured feathers,
whereas allele g does not produce a pigment,
so the chicken has white feathers. However,
this is also affected by the gene F/f. The
dominant allele, F, prevents the production of
coloured feathers, even if the bird has allele G

AUTOSOMAL LINKAGE

 When two or more gene loci are on the same

chromosome, they do not assort independently in
meiosis as they would if they were on different
chromosomes. The genes are said to be linked. They
stay together in the same combinations as in the
parents, and are said to be linked. Autosomal linkage
involves the autosomes – that is, all of the
chromosomes except the sex chromosomes.
AUTOSOMAL LINKAGE & CROSSING OVER

 Complete linkage between genes on the same chromosome is very rare. You have seen
that, during prophase I of meiosis, homologous chromosomes swap pieces of chromatids.
Alleles from one homologous chromosome can therefore change places with alleles from
the other. You may remember that this is called crossing over. Crossing over breaks the
linkage between genes on the same chromosomes.
 Most of the offspring
of this cross have
their parents’
combinations of
characteristics –
that is, either
striped body,
normal antennae or
ebony body,
aristopedia
antennae. These are
called parental
types. They are in a
1:1 ratio. If linkage
is complete, you
would expect all of
the offspring to be like this – which is exactly what happened with the test cross
involving the male Drosophila
 But when the female is involved in this test cross, some flies are produced that have
different combinations of characters. Some have striped body and aristopedia antennae,
and some have ebony body with normal antennae. These are called recombinants.
 They result from crossing over, which ‘recombines’ the characteristics of the original
parents. The two recombinant classes themselves are in a 1 :1 ratio.
 Crossing over between two gene loci is more likely to take place if the genes are further
apart, because there is more length of chromosome between them that can cross over.
You can use this to get an idea of the positions of genes on a chromosome. The more
recombinants you get in the offspring, the more crossing over has taken place, and the
further apart the genes are.
THE CHI-SQUARED (X2) TEST
 If you look at dihybrid inheritance, you will see that a 9:3:3:1 ratio of phenotypes is
expected in the offspring. It is important to remember that this ratio represents the
probability of getting these phenotypes, and it would be surprising if the numbers came
out absolutely precisely to this ratio.
 But just how much difference might scientists be happy with, before they began to worry
that perhaps the situation was not quite what they had thought?
 To answer this question, you can use a statistical test called the chi-squared (χ 2 ) test.
This test allows you to compare the observed results with the expected results and
decide whether or not there is a significant difference between them.
 The first stage in carrying out this test is to work out the expected results. These and the
observed results are then recorded in a table.
 You can then calculate the difference between each set of
results, and square each difference. (Squaring gets rid of any
minus signs – it is irrelevant whether the differences are
negative or positive.)
 Then you divide each squared difference by the expected
value, and add up all of these answers.

 So now you have a value of χ2 . Next you have to work out what it means. To do this, you
look in a table that relates χ2 values to probabilities.
 In this example, a probability of 0.05 is taken as being the critical one. If your χ 2 value
represents a probability of 0.05 or larger, then you can be fairly certain that the
differences between your observed and expected results are due to chance – the
differences between them are not significant. However, if the probability is smaller than
0.05, then it is likely that the difference is significant, and you must reconsider
assumptions about what was going on in this cross.
 And to work out the number of degrees of freedom, simply calculate the number of
classes of data minus 1. Here you have four classes of data (the four possible sets of
phenotypes), so the degrees of freedom are: 4 –1=3.
  Now, at last, you can look at Table 16.4 to determine whether the results show a
significant deviation from what was expected. The numbers in the body of the table are χ
2 values. You look at the third row in the table (because that is the one relevant to 3
degrees of freedom), and find the χ2 value that represents a probability of 0.05. You can
see that this is 7.82. The calculated value of χ2 was 0.79. So your value is a much, much
smaller value than the one you have read from the table. In fact, there is nothing like this
number in the table – it would be way off the left-hand side, representing a probability of
much more than 0.1 (1 in 10) that the difference in your results is just due to chance. So
you can say that the difference between the observed and expected results is very likely
to be due to chance, and there is no significant difference between what was expected
and what actually happened.
 As in other statistical tests, you often use a null hypothesis when using χ 2 . The null
hypothesis is that there is no difference between your observed and expected results. In
other words, the null hypothesis says that any difference between the observed and
expected results is due to chance. In this example, the χ 2 value you have calculated
supports the null hypothesis.

GENES, PROTEINS AND PHENOTYPE

 In this section a different convention is used for symbols for alleles of human genes.
Previously, you have used a single letter, but now you will use the general convention for
most human genes of a three-letter abbreviation, written in italics. The same
abbreviations are used by all scientists whose work involves these genes. For example,
the gene for producing tyrosinase is shown as TYR. The same three-letter code shown in
normal type (not italics), TYR, represents the protein or polypeptide that the gene codes
for.

THE TYR GENE, TROSINASE AND ALBINISM

 In albinism the dark pigment melanin is totally or partially missing from the eyes,
skin and hair. In humans this results in pale blue or pink irises in the eyes and
very pale skin and hair.
 The pupils of the eyes appear red. The condition is often accompanied by poor
vision, rapid, jerky movements of the eyes and a tendency to avoid bright light.
  The TYR gene is found on the
long arm of chromosome 11.
There is a faulty recessive allele
that results in albinism. About 1
in 17 000 children born worldwide are homozygous recessive for this allele and
therefore show albinism. However, the condition is relatively common in some
populations, such as the Hopi in Arizona and the Kuna San Blas Indians in
Panama.
 A recessive allele of the gene for the enzyme tyrosinase results in either the
absence of tyrosinase or the presence of inactive tyrosinase in the cells where
melanin is made. Tyrosine cannot be converted into DOPA and dopaquinone. The
first two steps of the conversion of the amino acid, tyrosine, into melanin
therefore cannot take place.
 Tyrosinases occur in plant as well as in animal tissues. The action of the enzyme
can be seen in the blackening of a slice of potato left exposed to the air

THE HBB GENE, HAEMOGLOBIN AND

SICKLE CELL ANEMIA

 HBB is the gene that codes for the amino acid sequence in the β-globin
polypeptide in haemoglobin. It is found on the short arm of chromosome 11.


 This small difference in the amino acid sequence makes little difference to the haemoglobin
molecule when it is combined with oxygen. But when it is not combined with oxygen, the
‘unusual’ β-globin polypeptides make the haemoglobin molecule much less soluble.
 The molecules tend to stick to each other, forming long fibres inside the red blood cells.
The red cells are pulled out of shape, into a half-moon or sickle shape. When this
happens, the distorted cells become useless at transporting oxygen. They also get stuck
in small capillaries, stopping any unaffected cells from getting through.
 A person with this unusual β-globin can suffer severe anaemia (lack of oxygen
transported to the cells) and may die. Sickle cell anaemia is especially common in some
parts of Africa and in India.
  A person with one copy of the normal HBB allele and one copy of the sickle cell allele
makes some normal haemoglobin and some sickle cell haemoglobin. They generally
show no symptoms unless they are in conditions where there is excessive oxygen
demand by their muscles – for example, exercising very vigorously.

THE F8 GENE, FACTOR VIII AND HAEMOPHILIA

 The F8 gene contains the code for synthesising a protein called coagulation factor VIII.
The protein is synthesised in liver cells. It is secreted into blood plasma and plays an
important role in the sequence of events that takes place during blood clotting.
 Abnormal alleles of this gene result in the production of abnormal forms of factor VIII
protein, less factor VIII than usual, or even no factor VIII at all. This means that blood
does not clot normally, and excessive bleeding can follow from even a small injury. The
condition is called haemophilia.
 The F8 gene is found on a non-homologous region of the X chromosome. This means that
it is a sex-linked gene. Males have only one copy and cannot therefore mask the effect of
the faulty allele with a normal one. Females can be heterozygous for this condition
without showing any symptoms at all, as only one copy of the normal gene is required to
result in the synthesis of enough factor VIII.

THE HTT GENE, HUNTINGTIN AND HUNTINGTON’S DISEASE

 The locus of the HTT gene is on chromosome 4. This gene codes for the production of a
protein called huntingtin. Scientists still do not know exactly what this protein does, but
it is known to be important in the development of neurones, particularly in the brain.
 In some people, the nucleotide sequence of this gene contains a large number of
repeated CAG triplets. (This is sometimes called a ‘stutter’.) If the number of repeats is
over 40, neurone development is abnormal and the person develops Huntington’s
disease.
 (If repeats number between 36 and 39, the disease sometimes develops but sometimes
not.) The condition develops gradually as a person gets older, and often no symptoms
show until the person is 30–40 years old. They begin to lose their ability to control
movements and to walk, talk or think clearly. The condition is fatal, with death occurring
within 15–20 years after symptoms first appear.
 This faulty allele is dominant. There is therefore a one in two chance that a person with a
parent with the allele will inherit the condition. As the condition may not be noticed until
the person is adult, they may have had children before they knew of the possibility of
passing on Huntington’s.

THE LE GENE, GIBBERELLIN AND STEM ELONGATION

 The height of some plants is partly controlled by their genes. For example, tallness in pea
plants is affected by a gene with two alleles, Le and le. If the dominant allele, Le, is
present, the plants can grow tall, but plants homozygous for the recessive allele, le,
always remain short. The dominant allele of this gene regulates the synthesis of the last
 enzyme in a pathway that produces an active form of gibberellin, GA1 . Active gibberellin
stimulates cell division and cell elongation in the stem, so the plant grows tall.

 A recessive allele of this gene has one nucleotide that differs from the normal allele. This
allele codes for alanine instead of threonine at one position in the primary structure of
the enzyme near its active site, producing a non-functional enzyme. Homozygous plants,
lele, are genetically dwarf as they do not have the active form of gibberellin. Applying
active gibberellin to plants which would normally remain short, such as cabbages, can
stimulate them to grow tall.

CONTROL OF GENE EXPRESSION

GENE CONTROL IN PROKARYOTES

 An understanding of how genes are ‘switched on and off’ first came from studies in
bacteria. One of the moststudied genes is the one that codes for the production of the
enzyme β-galactosidase (also known as lactase). This enzyme is used by some bacteria to
hydrolyse lactose in the bacterium’s environment to glucose and galactose, which can
then be absorbed and used as an energy source by the cell.
 The gene that codes for the production of β-galactosidase is an example of a structural
gene. A structural gene is one that codes for the production of a protein that is used by
the cell. Some structural genes live up to their name by coding for proteins that become
part of a structure in the cell, but many structural genes have other roles, such as coding
for enzymes.
 The expression of the lactase gene is controlled by other genes that lie close to it on the
circular DNA (DNA molecule). These are called regulatory genes.
 Structural and regulatory genes that work together are generally found in a group, and
this cluster of genes is called an operon. The operon that is responsible for the
production of lactase in bacteria is called the lac operon.
 In the bacterium Escherichia coli, the number of molecules of β-galactosidase present in
a cell varies according to the concentration of lactose in the medium in which the
bacterium is growing. The quantity of the enzyme is altered by switching the
transcription of the β-galactosidase gene on or off.
 The lac operon also contains other structural genes, besides the one that codes for β-
galactosidase. There are three structural genes altogether:
 lacZ, coding for β-galactosidase
 lacY, coding for permease (which allows lactose to enter the cell)
 lacA, coding for transacetylase.
 Transcription of all of these genes is controlled by the same promoter, and they are all
transcribed at the same time. The sequence of events when there is no lactose in the
medium in which the bacterium is growing is as follows.
 The regulatory gene codes for a protein called a repressor.
 The repressor binds to the operator region, close to the gene for β-galactosidase.
 Because the repressor is attached to the operator, RNA polymerase cannot bind
to DNA at the promoter region.
 As a result, there is no transcription of the three structural genes.
 The repressor protein has two binding sites. This repressor protein can bind to DNA at
one site and to lactose at the other. When lactose binds to its site, the shape of the
repressor protein changes so that the DNAbinding site is closed.

 When lactose is present in the medium in which the bacterium is growing, the following
processes occur.
 Lactose is taken up by the bacterium.
 Lactose binds to the repressor protein, distorting its shape and preventing it
from binding to DNA at the operator site.
 Transcription is no longer inhibited and messenger RNA is produced from the
three structural genes
 The genes have been switched on and are transcribed together. The bacterium can now
absorb and break down lactose.
 This mechanism allows the bacterium to produce β-galactosidase, permease and
transacetylase only when lactose is available in the surrounding medium and to produce
them in equal amounts. It avoids the waste of energy and materials in producing
enzymes for taking up and hydrolysing a sugar that the bacterium may never meet.
However, the sugar can be hydrolysed when it is available.
 The enzyme β-galactosidase is an inducible enzyme. This means that it is synthesised
only when its substrate is present. The presence of the substrate induces (causes) the
transcription of the gene for the enzyme. The binding of the effector molecule (which in
this case is lactose) to the repressor prevents the repressor from binding to the operator,
the repressor is released and transcription proceeds.
 The production of other enzymes, called repressible enzymes, is controlled in a slightly
different way. Here, the binding of the effector molecule to the repressor helps it to bind
to the operator. So the repressor attaches to the operator region, which stops
transcription.
TRANSCRIPTION FACTORS IN EUKARYOTES

 Eukaryotes do not have operons as prokaryotes do. Instead, the expression of genes in
eukaryotes is controlled by transcription factors.
 A transcription factor is a protein that binds to DNA and affects whether or not a gene is
transcribed. The role of transcription factors is to make sure that genes are expressed in
the correct cell at the correct time and to the correct extent.
 In humans, for example, about 10% of genes are thought to code for proteins that act as
transcription factors.
 Some transcription factors bind to the promoter region of a gene, either allowing or
preventing its transcription. Their presence either increases or decreases the rate of
transcription of a gene.
 There are many different types of transcription factors, which have different effects.
Scientists have probably discovered only a small proportion of them so far, and research
continues to find new ones and increase understanding of how they work. Some
examples of the effects of transcription factors include the following.
 General transcription factors are necessary for transcription to occur. They form
part of the protein complex that binds to the promoter region of the gene
concerned.
 Other transcription factors help to ensure that a number of different genes are
activated in the correct sequence. This is important to allow the correct pattern
of development of body regions as a zygote gradually becomes an embryo and
then a fetus.
 A transcription factor is responsible for the determination of sex in mammals.
 Transcription factors allow responses to environmental stimuli, such as
switching on the correct genes to respond to high environmental temperatures.
 Some transcription factors, including the products of proto-oncogenes and
tumour suppressor genes, regulate the cell cycle, growth and apoptosis
(programmed cell death).
 Many hormones, such as testosterone, have their effect through transcription
factors.
 Transcription factors act in similar ways in plants and animals. You saw that the plant
hormone gibberellin controls seed germination in plants such as wheat and barley by
stimulating the synthesis of amylase. This is a good example of how a hormone can
influence transcription. If gibberellin is applied to barley seeds, there is an increase in
the transcription of mRNA coding for amylase.
 Gibberellin has this effect by causing the breakdown of DELLA proteins. A molecule
known as a DELLA protein is a repressor protein. DELLA proteins normally inhibit the
binding of a transcription factor, such as phytochrome-interacting protein (PIF), to a
gene promoter. Gibberellin causes the breakdown of the DELLA protein, which allows
PIF to bind to its target promoter. Transcription of the gene can then take place,
resulting in an increase in amylase production.