nucleic acids · the monomers of nucleic acids are called nucleotides. there are two major classes...
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Nucleic Acids
Nucleic acids are one of the 4 major macromolecules found in all living things. A
macromolecule is also known as a polymer, which means it is a large molecule made of
smaller repeating subunits known as monomers. The monomers of nucleic acids are
called nucleotides.
There are two major classes of nucleic acids:
1) DEOXYRIBONUCLEIC ACID (DNA)
DNA is the chemical basis for the gene, the fundamental unit of inheritance and is
responsible for governing the activities of the entire cell. DNA is mainly found in the
nuclei of cells but is also present in the mitochondria.
2) RIBONUCLEIC ACID (RNA)
RNA molecules are mainly found in the cytoplasm of cells and perform various tasks,
such as acting as structural scaffolds or being chemical messengers. There are a
variety of different forms of RNA including, mRNA, tRNA, and rRNA.
Nucleotides:
A nucleotide consists of three parts:
i) A nitrogenous base
(so called because nitrogen atoms form part of
the rings of the molecule)
There are two types of nitrogenous bases, purines
and pyrimidines.
In DNA, there are two purine bases, adenine and guanine and two pyrimidine bases,
thymine and cytosine that are used to make nucleotides.
In RNA, adenine, guanine and cytosine occur, but thymine does not, it is replaced by the
pyrimidine uracil.
Pyrimidines
(single ring)
Purines
(double ring)
ii) A 5-carbon sugar (in DNA it is deoxyribose; in RNA it is ribose)
iii) A phosphate group
A nucleic acid polymer consists of alternating chains of sugar and phosphate, with a
nitrogenous base attached to a deoxyribose (or ribose) sugar. The nucleotide is held
together by covalent bonds that are known as a phosphodiester bond.
A molecule of RNA is a single-stranded structure that often becomes folded, while
DNA takes on a double stranded, helical formation. In DNA, bonds are formed between
nitrogenous base pairs and are held together through hydrogen bonding.
The nitrogenous base pairs between the DNA double helix always pair up such that
adenine and thymine are together and guaninie and cytosine are joined.
Nucleotides are not only important as building blocks of nucleic acids; they also have
important functions in their own right. Most of the energy being put to use at any given
moment in any living organism is derived from the nucleotide adenosine triphosphate
(ATP).
Deciphering the Genetic Code
Genes and Chromosomes
The gene is the major functional sub-unit of DNA. Genes are specific sequences of
DNA that have the potential to be expressed and to guide an organism’s development.
We often think of genes as the portion of inherited information that defines one
particular trait of an organism’s physical characteristics.
The sum of the entire DNA including all of the genes (20 000 - 25 000) within a cell is
referred to as the genome.
The specific number, type and arrangement of genes are unique to each species, but
even organisms that are only
distantly related may carry very
similar genes.
In humans genes are organized
onto chromosomes. Each
chromosome contains linear
double-stranded molecules. DNA
molecules are held together with
proteins called histones. A
chromosome is actually 60%
protein, 35% DNA, 5% RNA.
Genes are not spaced regularly
along chromosomes. The density of
genes can vary from one
chromosome to another. For
example, in humans:
Chromosome 4 – 1.3 billion base pairs = 200 genes
Chromosome 19 – 72 million base pairs = 1450 genes
There is no set relationship between the number of genes on a chromosome and the total length of the chromosome
Central Dogma
DNA provides the information that ultimately codes for a specific protein to be
produced. This is a two-step process of transcription, followed by translation.
DNA
Nucleus transcription
mRNA
Cytoplasm translation
Proteins
Transcription is a process that
occurs within the nucleus, where
the information from one gene is
used as a template to produce a
complementary strand of RNA
nucleotides (mRNA) that is then
moved into the cytoplasm.
Translation is the process where the mRNA
transcript is used to generate a sequence of amino
acids, which will eventually fold into a three-
dimensional structure and become an active protein.
This process occurs in the cytoplasm of cells and
requires a number of accessory molecules (rRNA
and tRNA).
Information for the genetic code is read as a series
of three consecutive bases or codons. Each codon
ultimately corresponds to a specific amino acid that
will be added to a growing polypeptide chain.
Mutations A mutation is any type of heritable genetic
change. There are several types of
mutations, some which go unnoticed; others
are beneficial, while others still may have
serious, deleterious effects.
The following are common mutations that
can occur during replication:
Base Substitution
A different nucleotide is substituted.
Examples:
Silent - same amino acid is specified
Mis-sense - a different amino acid is
specified
Non-sense - codon changed to a stop
Frameshift mutation
Addition or deletion of a base can throw
reading frame off
Example:
SEETHEREDCATANDTHEFATDOG
SEEHEREDCATANDTHEFATDOG
Even without exposure to mutagens, each
of your genes undergoes thousands of
mutations during your life; most of these
are corrected by repair enzymes.
Cell Division
You are made up of approximately 100 trillion cells. This is amazing considering that all these cells started from one fertilized egg. Even now
cells are dividing in your body! Cell division is needed for:
1. Growth - organisms increase in size by creating more cells
2. Repair - old and damaged tissue is replaced by new cells
3. Reproduction – single celled organisms reproduce by splitting in two
How does cell division occur?
Cell division occurs in three stages:
1. Replication – Making an exact copy of DNA
The replication process must be relatively quick and it must be accurate
for cells to survive. Remarkably, cells are able to duplicate their DNA in
a few hours, with an error rate of approximately one per billion
nucleotide pair!
2. Mitosis - The division of chromosomes in the nucleus
3. Cytokinesis - The division of the cytoplasm and cell organelles
The end result of these stages are TWO identical cells from one original
cell.
In order to describe the events of the cell cycle, the process has been
divided into several phases:
INTERPHASE:
The cell is doing its job
DNA in the form of chromatin – cannot be
seen
Cell grows
At the end of interphase the DNA has
replicated
PROPHASE:
Nuclear membrane disappears
Nucleolus disappears
DNA shortens and thickens and becomes
visible - chromsomes
Spindle fibres form and can be seen
Centrioles move apart
METAPHASE:
Chromosomes line up at equator of cell
Centrioles are located at poles
Spindle fibres attach to centromeres and
centrioles
ANAPHASE:
Centromeres split and single-stranded
chromatid move to opposite poles
Pulled by spindle fibres
TELOPHASE:
Opposite of prophase
Nuclear membrane reappears
Nucleolus reappears
Spindle fibres disappears
Chromatid become longer and
thinner and cannot be seen
(chromatin)
FINAL RESULT OF CELL DIVISION:
Cytokinesis occurs (division of
cytoplasm)
Two genetically identically daughter
cells
Meiosis
Different characteristics are displayed by different people. This variation in
characteristics is shown because each person comes from a different family. Even
within a family there are differences.
Each human cell has 46 chromosomes in total or 23 pairs of chromosomes. Each pair of
chromosomes resembles each other in size, shape and genetic information. You receive
one member of each pair from your father and the other from your mother. These
pairs of chromosomes are called homologous chromosomes. Your genes are located on
these chromosomes.
Meiosis is the process by which a diploid cell (2n) produces haploid (n) gametes or sex
cells.
Meiosis occurs only in the sex organs of most living things:
Spermatogenesis = sperm production in the testes
Oogenesis = egg/ovule production in the ovaries
Plants = pollen (microspores) in the anther and ovules/eggs (megaspores) in the ovaries
Meiosis Terminology
Diploid
Two sets of chromosomes (2n)
Body cells (somatic) are diploid cells
Human cells have 46 chromosomes or 2 sets (2n) of 23 chromosomes
Haploid
Single set of chromosomes (n)
Sperm or egg (gametes) are haploid cells
Human sex cells have 23 chromosomes
Homologous chromosomes (homologues)
Two chromosomes similar in shape and size that carry the same genetic information
Inherit one chromosome from each parent
Zygote
The cell that results when an egg and a sperm unite (fertilization)
Synapsis
The pairing of homologous chromosomes
Occurs in prophase I of meiosis
Tetrad
Two homologous chromosomes form a loose connection of 4 chromatids
Crossing over
The process where the ends of chromosomes (adjacent) become twisted or tangled
together and break apart
The ends of the homologous chromosomes may switch or exchange places
Explains why all offspring will be different (except identical twins)
Non-disjunction
During meiosis one chromosome does not get pulled to the proper end of the cell
One cell may get too many chromosomes and others too few
Stages of Meiosis (Interphase occurred first)
Phase Diagram Key events
Prophase I
Same as prophase of mitosis
Nuclear membrane and
nucleolus disappear
Chromosomes become visible
(previously chromatin)
Spindle fibres appear
Synapsis occurs as homologous
chromosomes pair up
The exchange of information
occurs in a process called
crossing over
Metaphase I
Tetrads line up at the equator
of the cell
Chromosomes align randomly
and differently each time
through meiosis (law of
independent assortment)
Anaphase I
Tetrads separate and double
stranded chromosomes move to
the poles of the cell
Telophase I
Two cells forming, with ½ the
number of chromosomes
Each strand is different
because of crossing over
Chromosomes still must be
separated into single stranded
chromatid
Prophase II
Same as mitosis prophase
Metaphase II
Double stranded chromosomes
line up at the equator
Same as mitosis metaphase
Anaphase II
Double stranded
chromosomes separate
into single stranded
chromatids
Same as mitosis
anaphase
Telophase II
Four cells with the
haploid number of
chromosomes
Each cell is genetically
different from each
other and different
every time meiosis
occurs
Mendelian Genetics
Early Ideas About Genetics
Aristotle (384-322 BC) Pangenesis - every part of the body was involved in the production of the “seeds” of the
parents; seeds fused to give rise to a new individual.
Anton van Leeuwenhoek (1632-1723) The idea of an “animalcules” in the semen of males – a tiny preformed embryo.
19th Century
Blending theory of inheritance
Charles Darwin Offspring had variations of their parent's characteristics; but he could not explain why.
Gregor Mendel (1822-1884) Developed the fundamental principles that became the modern science of genetics.
Mendel’s Experiments
Gregor Mendel was a monk, whose studies included mathematics and botany. He
conducted a series of experiments on pea plants over an eight-year period.
Mendel used pure bred (or true breeding) pea plants for his experiments, which are
plants that produced predictable offspring (Example - tall or short).
Mendel actually studied seven different traits, each trait that had only two possible
variations. Mendel obtained pure bred plants through selective breeding.
Useful terminology:
P generation = Parent Generation
F1 generation = Offspring of parents (first filial generation)
F2 generation = Offspring of F1 (second filial generation)
Mendel bred pure breeding tall plants with
pure breeding short plants.
All of the offspring were tall. The tall
pea plants were then crossed with each
other.
The resulting offspring showed a 3:1 ratio
of tall plants to short plants.
These results led Mendel to conclude that the trait for tall plants must be dominant and
the trait for short plants to be recessive. When both a dominant and a recessive trait
are present, only the dominant one will manifest itself.
Mendel conducted theses experiments many times, using the seven different traits. For
each test, he obtained the same results.
In addition, Mendel came up with the Law of Segregation:
i) The inherited traits (or genes) are determined by pairs of ‘factors’ or alleles.
ii) The alleles segregate (or separate) in the formation of gametes (eggs or sperm)
iii) The alleles are inherited – one from each parent.
Using the information obtained from Mendel’s
experiments, we can look at his experiments
again from the point of view that every trait is
associated with a different allele.
Symbols are assigned to the alleles. Capital
letters for dominant traits and lower case for
recessive.
Examples: T = tall and t = short
The genotype are the alleles for a
particular trait.
The phenotype is how the alleles
physically manifest themselves.
Genotypes can be either homozygous
or heterozygous.
Homozygous means that both of the
alleles are the same (TT or tt).
Heterozygous means the two alleles
are different (Tt).
Punnett Squares
Comparing one trait at a time in breeding experiment is referred to as a monohybrid
cross. The results can be organized in a Punnett square; a way of calculating the
probability of inheriting a particular trait. It is a simple method of illustrating all
possible combinations of gametes from a given set of parents.
Examples:
In guinea pigs, black fur is dominant to white fur. What would the F2 generation look
like if you started with a male homozygous for white fur and a female homozygous for
black fur?
Cross a white furred male with a female from the F1 generation.
Test Cross A test cross is a type of breeding experiment that can be used if the phenotype of an
organism is known, but the genotype is unknown.
The test cross is always performed between the organism with an unknown genotype
(that carries a dominant allele – heterozygous or homozygous dominant) and an organism
that has a homozygous recessive genotype.
A test cross would NOT be employed to determine human genotypes.
Sample Problem:
Having blue flowers is dominant (B) is a dominant characteristic to the recessive trait of
having pink flowers (b). By performing a test cross with an plant of unknown genotype
that has blue flowers, determine the possible outcomes that could result.
When performing a test cross there are only two possible outcomes that can occur:
1. All offspring will appear to have the dominant trait. This would suggest that the
unknown organism has a genotype that is homozygous dominant.
2. Half the offspring would have the dominant trait and half would have the recessive
trait. This would suggest that the unknown organism has a genotype that must be
heterozygous.
Test crosses have proven to be a useful tool in the process of selective breeding.
Selective breeding is the crossing of desired traits from plants or animals to produce
offspring that have one or several of the desired characteristics.
Selective breeding commonly employs the techniques of either inbreeding or
hybridization.
Hybridization is the mating of two different parents to produce offspring with
desirable characteristics of both parents.
Inbreeding is the process by which mating occurs between closely related individuals
for the purpose of maintaining or perpetuating certain characteristics. Inbreeding can
often result in rare recessive features/conditions manifesting themselves.
Practice Questions
If you are given a dominant round (R) seed pea plant and you need to know the genotype
of this plant, you need to do a test cross. What pea plant genotype would you cross this
mystery dominant plant with?
In doing this cross, you find that the offspring are all round. What does this indicate
about the mystery parent genotype?
In doing this cross, you find that the offspring show a 1:1 ratio of round:wrinkled. What
does this indicate about the mystery parent genotype?
In corn, the allele for purple kernels is dominant to the alleles for yellow kernels.
Determine the likely genotypes of the parents if the offspring that results from
pollination produce 47 purple kernel producing plants and 14 yellow kernel producing
plants.
This idea of using the phenotypes of offspring to predict the genotypes of parents is
employed when studying human inheritance patterns. This is called Pedigree Analysis.
Pedigree Analysis
Pedigree chart: a graphic presentation of a family tree that shows the pattern of
inheritance for a single gene.
From the point of view of individual III - 1, the symbols represent the following relationships:
I - 1 = grandfather I - 2 = grandmother
II - 1 and II - 2 = aunts II - 3 = uncle II - 4 = father II - 5 = mother
III - 2 = fraternal twin sister III - 3 = brother
Practice Problem #1
The following Pedigree shows a family with the trait of shortsightedness. The allele for
shortsightedness (E) is dominant to the allele for normal vision (e). Predict the genotypes for
each individual in the family.
Practice Problem #2
Phenylketonuria (PKU) is a genetic disorder caused by a dominant allele. People with PKU are unable to metabolize a naturally occurring amino acid, phenylalanine. If phenylalanine accumulates it inhibits the development of the nervous system, leading to major cognitive delays. The symptoms of PKU are not evident at birth, but can develop quickly if the child is not placed on a special diet. The pedigree chart below shows the inheritance of the defective allele in one family.
a) How many generations are shown in the pedigree?
b) How many children were born to the parents of the first generation?
c) What are the genotypes of individuals 1 and 2 in generation I?
d) How is it possible that in generation II, some of the children showed symptoms of PKU,
while others did not?
e) Individuals 6 and 7 in generation II had a child without PKU. Does this mean that they
can never have a child with PKU? Explain your answer.
Incomplete Dominance and Codominance
Not all alleles interact under the principle of dominance and recessive. Incomplete
dominance is when both alleles contribute equally to the phenotype of the organism,
creating a blend of traits in a heterozygous genotype.
Example:
In four o'clock flowers, red flowers (CR) is incompletely dominant to white (CW). The
heterozygous plants (CRCW) are pink in colour. What are the possibilities for the F2
generation starting with a cross between a red and white flower?
Codominance: Two dominant alleles are expressed at the same time. No blending.
Example:
In cattle, red hide colour (R) is codominant to white (W). Cows that are heterozygous
for this trait have a roan hide colour (RW), where the red hair and white hair both
appear on the animal.
Cross two roan cows and determine the chance of getting a white animal.
Sometimes it is a benefit for an individual to inherit two different alleles for the same
trait. This is called heterozygous advantage. An example is a person who is
heterozygous for the sickle cell gene; they have some normal red blood cells and are
resistant to malaria.
Dihybrid Crosses 1. What is the frequency of tossing one dice and having it roll the number one?
2. What is the frequency of tossing two dice and having both roll one?
3. What is the frequency of tossing a Yahtzee! Five dice that all roll the number one?
The above examples illustrate that the result of one toss of the dice has no affect on
the outcome of future rolls, that is, one’s dice action is segregated from the others and
independent.
In his studies Gregor Mendel discovered that like the dice, alleles assort independently
from each other. Mendel termed this, The Law of Independent Assortment. The law
states that:
If genes are located on separate chromosomes, then they will be inherited independently of each other.
This simply means that the inheritance of alleles for one characteristic does not affect
the inheritance of alleles for another characteristic (as long as the alleles are on
different chromosomes).
Example:
Whether a human has attached or free earlobes has no effect upon whether or not
their hair is curly or straight. The characteristics are independent from one another.
Mendel came up with the idea for the law of independent assortment while studying the
inheritance of two separate traits in crossbreeding (following the same procedures he
had used for studying single traits). This kind of approach is called a dihybrid cross.
There are two approaches we can take to determine the probability for each of the
possible outcomes to occur in a dihybrid cross.
Approach #1
You can solve a dihybrid problem by completing two separate monohybrid crosses, one
for each of the characteristics being examined. Then the crosses can be combined to
calculate the probabilities of the dihybrid crosses.
Example:
In garden pea plants the pod colour yellow (Y) is dominant over the recessive allele
green (y); while round seed shape (R) is dominant over wrinkled (r). Following mating
between parents with the genotypes YyRr x YyRr, what are the probabilities of
obtaining offspring with the following characteristics:
Yellow pods and round seeds
Green pods and round seeds
Yellow pods and wrinkled seeds
Green pods and wrinkled seeds
Pod Colour Probability Seed Shape Probability Combined
Probability
Yellow Round
Green Round
Yellow Wrinkled
Green Wrinkled
Approach #2
The alternative method to solving dihybrid problems has you come up with all the
possible combinations of alleles that can occur during a cross, and then completing a
giant Punnett square. The first step is to identify the complete genotype of each
organism in the cross (this will include 4 alleles, two for each trait being examined).
Using the previous example of Yellow (Y) and green (y) pea pods and round (R) and
wrinkled (r) pea seeds:
What is the probability of obtaining green and wrinkled peas?
Predict the chance of a yellow and round pea from the following parents:
yyRr x Yyrr
Multiple Alleles
Many traits in humans and other species are the result of the inheritance of more than
two alleles for one gene. A gene with more than two alleles is said to have multiple
alleles.
Blood Types In humans a single gene determines a person's ABO blood type. This gene determines
what type of an antigen protein, if any, is attached to the cell membrane of red blood
cells. An antigen protein is a molecule that stimulates the body's immune system. The
gene is designated "I" and it has three common alleles: IA, IB and i. The different
combinations of the three alleles produce the four different phenotypes of blood.
A & B are dominant to O. A & B are codominant. The possible genotypes for blood typing
are:
IAIA - IBIB -
IAi - IBi -
IAIB - ii -
Examples:
A man with hybrid type A blood and a woman with type AB blood wish to know the
possible blood types for their children.
A rich couple are confronted by a man who claims to be the man's son from a previous
marriage. The son's blood type is "O" and both the man and his ex-wife are hybrid type
A. What is the probability that the young man is telling the truth?
Rh Factor
In addition to the substances that cause A, B, and O blood types there is another
factor called the Rh factor that can be found in blood. The genes for having the Rh
factor are completely dominant to the genes for not having the Rh factor.
For example: Let: R - have the Rh factor
r - absence of the Rh factor
Therefore, RR and Rr produce people that are Rh positive & rr only produce an Rh
negative individual.
What are the possibilities for a man that is pure type B and pure Rh positive with a
woman who is hybrid A and Rh negative?
In addition to the many traits being controlled by one gene with multiple alleles, there
are also many traits that are polygenic, which means they are controlled by more than
one gene. Examples of polygenic traits include, height, skin colour and eye colour. These
traits tend to exhibit continuous variation in which the phenotype varies gradually from
one extreme to another.
Sex Linkage
Linked genes are genes that are on the same chromosome and that tend to be inherited
together. These genes DO NOT exhibit Mendel's law of independent assortment and
therefore do not follow the Mendelian inheritance patterns that have been previously
discussed.
Sex Determination
Human cells contain 46 chromosomes (23 pairs). The first 22 pairs are referred to as
autosomes; these chromosomes carry the majority of our traits. Your 23rd pair of
chromosomes are called your sex chromosomes; these are the ones that determines
your sex, but they also carry some traits. Males have one X and one Y chromosome
(XY), while females have two X chromosomes (XX).
Sex Linkage
Thomas Hunt Morgan (1866-1945) was an American geneticist who worked with fruit
flies (Drosophila melanogaster) and developed theories on gender and inheritance.
Fruit flies are an ideal subject for study in genetics because:
They reproduce rapidly
Offspring can mate shortly after leaving the egg
Females produce over 100 eggs each mating
You can study many generations in a short period of time
They are small – can be housed in a single culture tube
Males can be easily distinguished from females.
Morgan’s Experiment
Morgan explained his experiments by concluding that the X and Y chromosomes contain
different genes, and that in his fruit flies, the Y chromosome does not carry the gene
to determine eye colour.
Morgan called characteristics that are controlled by genes located on the sex
chromosomes as sex-linked traits.
In humans there are numerous sex-linked traits:
Hemophilia
Nearsightedness
Colour blindness
Hairy ears (Y linked)
Juvenile Glaucoma
Muscular Dystrophy
Males and females produce the same amount of proteins coded by genes located on the
X chromosome. However, females have two copies of this chromosome while males only
have one. Experiments have shown that one of the X chromosomes in each female cell is
inactivated. Which one is inactivated is random, and therefore different X
chromosomes are active in different cells. The inactivated X chromosome is called a
Barr Body.
Sex-Linked Problems
What are the possible offspring for a cross between a normal female and a colour-blind
male
Let: X - Normal gene for colour-blind male
Xc - Recessive gene for colour-blindness
In humans, baldness is sex-linked and recessive to normal amount of hair. For hair
colour, black is incompletely dominant to blonde, heterozygous have brown hair colour.
Show the possible offspring for a man who is bald and had brown hair and a woman who
is blonde and a carrier for baldness.