1. GENETICS
DEFINITION
Genetics is the science that seeks to
understand, explain, and ultimately exploit
the phenomenon of heredity (i.e. the
transmission of biological characteristics of
organisms from one generation to the next –
from parents to offspring).

2. HISTORICAL BACKGROUND
The superficial facts of heredity have been
known to mankind since the prehistoric
time, hence the old-age saying, “like begets
like”.

3. Pondering on the intricacy of the hereditary
phenomenon one early naturalist had this to
say,
“It often happens also that the children may
appear like a grandfather and reproduce the
looks of a great grand-parent, because the
parents often conceal in their bodies many
primordial mingled in many ways, which
fathers hand on to fathers received from their
stock; from these Venus brings forth forms
with varying lot, and reproduce the
countenance, the voice, the hair of their
ancestors

4. However the mechanism of the
phenomenon has eluded the inquisitive
mind of man for ages until the basic facts
of biology, particularly those concerned
with reproduction became known
towards the end of the nineteenth
century and beginning of the twentieth
century.

5. Up until late 19th century work on the
genetic phenomenon had been investigated
along two main lines of approach, namely:
 the identification of the physical nature of
the genetic material
 the understanding of the manner by which
biological characters are inherited.

6. Since before the dawn of the 20th century
very little was known about either
phenomenon these lines of investigation
were pursued separately.

7. IDENTIFICATION OF GENETIC
MATERIAL
In the very early days of investigation of the
genetic phenomenon it was thought that
biological materials could arise
spontaneously from decaying matter.
However this belief was later disproved
through a series of experiments in which it
was shown that no organisms developed in
sealed flasks containing boiled organic
matter.

8. Latter, with the development of the
science of classification of biological
organisms into separate and distinct
species it became evident that organisms
of one species could only give rise to
organisms of the same type.

9.  Since spontaneous generation of organisms
implied non-fixity of species the theory was
finally dropped in favour of the theory of
continuity of life which propounded that new
organisms arise only through the continuity
of life.

10.  After the general acceptance of the concept
of a continuous transfer of living material
between generations several theories were
proposed to explain how the transfer could
be effected.
 It was generally accepted at least that an
organism develops from a miniscule piece of
transmitted matter, though the physical
nature of the matter remained controversial.

11.  Some workers believed that an organism
developed from a substance received
from the female egg and a contribution of
form received from the male seminal
fluid.
 Latter, after the discovery of sex cells
(i.e. the egg and sperm) it was theorized
that one of the sexes contained within it
the entire organism in perfect miniature
form which could develop into its
preformed adult proportions – the pre-
formation.

13. However latter it was demonstrated that
different adult structures develop from
uniform embryonic tissues which provide
no clue as to their ultimate fate.

14. This led to the replacement of the pre-
formation theory by another concept which
propounded that tissues, organs, and
many other new factors which were not
present in the original formation of an
organisms appeared in the course of
development of the organism.

15. The appearance of the organs was
believed to arise entirely through
mysterious vital forces - the epigenetic
concept.

16. This view was later modified by the
proposition that organs arose through a
gradual transformation of increasingly
specialized tissue.

17.  It was latter advanced that an organism
developed from very small invisible
components (gemmules) which were exact
copies of each body organ.
 These were thought to be transmitted by the
blood stream to the sex organs where they
assembled into gametes.

18.  Upon fertilization mixture of paternal and
maternal organs and tissues would be
constituted, followed by the distribution of
the miniature elements to different parts of
the body during development.

19. This theory was well received by believers of
evolution since it provided an explanation of
how heritable changes could occur, leading
to the appearance of new species.

20. It was propounded that each of these
hereditary agents had a spiritual conscious
like property that could perceive and
interpret messages from the outside.

21.  Thus, for example, the excess use or disuse
of an organ would change its gemmules and
consequently lead to a changed inheritance
in the descendants.

22. This theory was however quickly disproved by
empirical experimentation – the work of John
Lamark.

23. Instead it was advanced that multi-cellular
organisms give rise to two types of tissue,
i.e. somatic and germplasmic tissue.
Somatic tissue was considered to be
essential for life processes of the
organism but was not capable of sexual
reproduction.
 Thus changes occurring in somatic
tissues could not be passed on in heredity.

24. On the other hand, germsplasmic tissue
is capable of reproduction and hence
any changes occurring within it could
lead to altered inheritance.

25. The germplasm was considered to be
transmitted from one generation to the
next and accounted for the many
biological similarities between
ancestors and descendants.

26. An end to the early beliefs and theories
concerning the nature of hereditary
material approached with the advent of
microscope, and hence the consequent
detailed knowledge of cell structure and
cell division.

32. At first the nucleus was shown to be
directly involved in fertilization through the
union of the sperm and egg nuclei.

33. Latter dark staining nuclear threads (latter
named chromosomes) were shown to
divide longitudinally during cell division,
with passage of equal portions of the
material to the two daughter cells

38. The total number of the threads was shown
to be constant in each cell of an organism
and species except for gametes which
contained half the number of threads in
other cells.

49. However, the number of nuclear threads
was shown to be restored when the nuclei
of the gametes fused during fertilization to
form the first embryonic cell.

50.  These observations provided the first clue
regarding the transmission of hereditary
factors from one generation to the next.

51.  Since the splitting of the parental
chromosomes occurred longitudinally, and
since the chromosomes of the offspring were
equal to the number of parental
chromosomes it was reasoned that the link
between parents and offspring occurred
through gametes.

52. TRANSMISSION OF GENETIC MATERIAL
Meanwhile, in another scenario, the
mechanism of heredity was being
investigated by crossing different parental
stocks exhibiting contrasting visible
characteristics and observing the outcome
in the offspring.

53.  Originally it had been long believed
heredity was a blending process whereby
the different parental characteristics
blended with each other.

54.  This belief however was dismissed by
observations that offspring often resembled
one or the other parent.

55. This led to speculations that parents
could contribute quantitatively
differently to the inheritance of the
offspring.
The direction of the wind at fertilization
was also believed to affect the
transmission of heredity to offspring.

56. These problems were settled with Mendel's
discovery that the appearance of
characters in heredity followed specific
laws.

58. Mendel showed that the hybrid between two
parental types of organisms, which had
differed in single character, would produce
two types of gametes in equal numbers.
Each type of gamete was an unchanged
descendant of one of the original parental
gametes.

62.  It soon became apparent from
Mendel's findings that each hereditary
unit (i.e. gene) must be inherited
between generations such that each
descendant has a physical copy of
the material, and that the material
must provide information to its carrier
as to structure, function and other
biological attributes of the organism.

66.  According to this contention there was
no blending or dilution of inheritance
whatsoever and inherited characters
were determined by discrete units
which remained unchanged in the
hybrid

67.  When Mendel's findings were discovered
forty four years latter they were found to fit
quite well with the particulate nature and
behaviour of individual chromosomes
during cell division.
 Consequently chromosomes were
pinpointed as carriers of hereditary units
(genetic material).

68.  Thence the science of modern genetics was
born and proceeded along the line that an
actual hereditary material existed, that it was
particulate in nature, and that its
transmission from one generation to the next
could be predicted.

69. NUCLEIC ACIDS
 Although the correspondence
between the events of cellular
division and the transmission of
Mendelian characters finally led
scientists to identify the nucleus and
its constituent chromosomes in
particular as carriers of genetic
material the nature of the genetic
material itself had not been identified
by the end of the nineteenth century.

70.  By this time however, methods of
separating nuclei from cytoplasm had
been developed. Later an acid
containing a large amount of
phosphorus was extracted from the
nucleus.

71.  The acid, named nucleic acid, proved to be
a constant feature of all cells.
 Soon it was shown that the acid could be
broken down into smaller sections or units
each of which consisted a sugar, a
phosphate group, and a nitrogen-
containing portion. The units were named
nucleotides.

72. It was further shown that the sugar in the
nucleotides was either a ribose or a deoxy-
ribose.

74.  No particular nucleic acid contained
both these sugars in its molecule.
Consequently two main types of
nucleic acids could be found.

75.  Those containing ribose sugar in their
molecule were named ribonucleic acids
(RNA) while those containing deoxy-ribose
sugar were named deoxy-ribonucleic acids
(DNA).

76.  RNA was found to occur mainly in the
cytoplasm while DNA occurred only in the
nucleus.

77.  The phosphate group of the nucleotides was
shown to be attached to the sugar at its
number 5 carbon position.
 Besides the sugar and phosphate groups
which were observed to be constant for all
nucleotides of all nucleic acids, a more
variable nitrogen-containing group was also
present, attached to the sugar at its number
1 carbon position.

79.  The nitrogen-containing group contained
either one or two carbon-nitrogen rings and
could function as a base.
 Bases containing one carbon-nitrogen ring
were named pyrimidines, while those
containing two rings were named purines.

81.  Two forms of purines (i.e. adenine and
guanine) were identified in both DNA and
RNA.
 Likewise two types of pyrimidines were
distinguished (i.e. cytocine and thymine) in
DNA while in RNA cytocine was substituted
by uracil.
 Each base distinguished the particular
nucleotide carrying it.

82.  From these observations therefore, it was
established that that nucleic acids are linear
polymers composed of four types of
nucleotides.
 In DNA the nucleotides are adenine, guanine,
cytosine and thymine, whereas in RNA the
nucleotides are adenine, guanine, cytosine
and uracil.

90.  Therefore four different types of
nucleotides were shown to occur in DNA
and in RNA.
 It was latter shown that the nucleotides
were connected together to form chains by
a series of phosphate-sugar bonds at
number 3 and 5 carbons of the sugar.

95.  By mid-twentieth century the DNA
molecule had been shown to consist
of a long chain of hundreds or
thousands of different nucleotides in
varied lengths and sequences.

96.  The length and variability of the DNA
molecule was consistent with the concept
that genetic material could contain different
types of information specifying all the
biological characteristics of an organism i.e.
both the sequence and length of the
nucleotide chain (DNA or RNA) could attain a
great degree of variability, each sequence
and length coding for a different biological
message.

97.  Later in the nineteenth forties x-ray and
other studies indicated that the DNA
molecule was a double strand.

99.  The bases of the double-stranded DNA were
shown to be quantitatively related such that
the total pyrimidine bases (thymine and
cytocine) were equal to the total purine
bases (adenine and guamine) i.e. T + C = A +
G, suggesting that base pairing was always
between a pyrimidine and a purine and never
between a pyrimidine and pyrimidine nor
between a purine and another purine.

100.  It was established further that each base
pair consists of a combination of one
purine and one pyrimidine connected
together by hydrogen bonds.

101.  Further it was shown that the pyrimidine
thymine was always paired to the purine
adenine (i.e. T-A) and the pyrimidine
cytocine was bonded to the purine guanine
(i.e. C-G).

106.  It was then confirmed that the DNA
molecule is a two-stranded structure and
coiled like a rope whose strands could be
separated only if the free ends were
permitted to revolve freely.

107. The coiling resembles a which staircase
has been twisted in opposite ways at the
end, with the strands composed of
phosphate-sugar linkages which are
repeated continuously, and interconnected
by complementary single purine or
pyrimidine bases.

110.  The great variability possible in the DNA
molecule and the ability of the molecule to
duplicate itself exactly suggested that the
DNA molecule was the very long sought
genetic material.
 Chemical analyses of chromosomes
showed that they contained large amounts
of DNA together with a histone-type
protein, which are now believed to
surround DNA. The chromosomes have
been shown to contain also small amounts
of RNA.

115.  Further quantitative results showed that the
amount of DNA in the nuclei of diploid cells
of an organism or species was relatively
constant, and that the amount was half as
much in haploid cells e.g. sperms.

117.  This corresponded to the relationship
between the diploid and haploid number of
chromosomes in cells. This suggested that
further that the DNA was the genetic material
sought for.

118.  Cyto-photometric studies with cell nuclei
also showed that the DNA remained
quantitatively constant in all nuclei of an
organism, except in haploid cells in which
the amount was only half that present in
diploid cells.

119.  The cyto-photometric technique involves
treating the nucleus with a warm acid,
followed by staining with a schiff's reagent.
This gives a reddish-purplish staining
reaction to the nucleus and is very specific
to DNA.
 Thus only chromosomes show this
reaction. By measuring the amount of light
transmitted through the stained nuclei it is
possible to determine quantitatively the
amount of DNA in the nuclei.

120.  It was shown further that the amount of
DNA doubled during the interphase stage
and was then equally distributed to two
daughter cells at anaphase. This again
corresponded with the behaviour of
chromosomes.

121.  With the above configuration it was possible
to explain how a DNA could replicate itself
exactly.

122.  It was explained that in order to replicate the
DNA molecule had to separate its strands
and then attract free-floating nucleotides to
pair with the bases of each strand. The
nucleotides would then be connected into
new strands with the aid of enzymes.

123. Thus it was concluded that the primer DNA
strand enters into a pairing relationship
with added free nucleotides which are then
zipped together by a polymerase enzyme.

125.  Further studies showed that new
nucleotides in a nucleotide chain were
added at number 3 carbon position of the
de-oxyribose sugar at one end of the chain.
 It was observed that if one of the deoxy-
ribonucleotides was absent in the reactants
then no DNA was synthesized.
 This suggested that the copying of a DNA
strand does not permit the existence of
gaps and that this copying proceeds
through complementary base pairing.

126.  The DNA molecule itself was synthesized in
vitro for the first time in 1957.
 This was done by mixing a previously formed
DNA with four different kinds of deoxy-
ribonucleotides in the form of triphosphates
in the presence of a polymerase enzyme and
magnesium ions.

127. REPLICATION AND SYNTHES OF
NUCLEIC ACIDS
 The most accepted explanation of the mode
of DNA replication is that each DNA strand
is a template or mould for its complement,
and a new helix has one old and one newly
synthesized strand.
 It has been suggested that replication
starts long before the unwinding of the two
complementary DNA strands is completed.
The two processes seem to proceed
simultaneously.

130.  Latter it was shown that a DNA molecule
can be synthesized in the absence of
primer DNA provided the different kinds of
nucleotides are mixed with polymerase
enzyme.
 The reaction, though has a long time lag to
occur. Eversince different DNA molecules
that do not occur naturally have been
synthesized in vitro.

131.  The RNA differs from DNA molecule first
because of its ribose sugar and also because
of the substitution of the pyrimidine thymine
by uracil in RNA.
 RNA is found throughout the cell

132.  Three main types of cellular RNA have been
identified, i.e. nuclear, ribosomal, and
soluble RNA. The latter two RNA's are
found in the cytoplasm.
 Each portion of RNA has been found to
represent a special function in the
synthesis of proteins.

133.  RNA appears to maintain a single strand
structure. Experimental evidence has shown
that, with very few exceptions from some
RNA viruses, all cellular RNA is of nuclear
origin and is derived from DNA templates.
The single strand then separates from the
DNA is derived from DNA templates

134.  Experimental evidence has shown that RNA
is copied from only one strand of DNA. The
DNA molecule splits and a single strand of
the molecule serves as a template upon
which a single strand of RNA is assembled.

135.  The free ends of the bases in the RNA strand
become connected in a new ribose-
phosphate-base sequence. The single strand
then separates from the DNA template and
passes into the cytoplasm.

136.  In RNA the absence of equality between the
base ratios of guanine to cytosine and
adenine to uracil implies a lack of
complementary pairing between the bases.
 This suggests that RNA generally maintains
a single-stranded structure. i.e. there is no
double-helix.

137.  Nevertheless RNA acquires stability from its
ability to fold back on itself, so that
occasional base pairing and hydrogen
bonding enables some form of paired helical
structure.