Genetic Variation

Genetic Inheritance & Variation

No 2 organisms in a sexually reproducing

species are the same (except clones or

monozygotic twins)
Genetic variation is essential for evolution
and change to occur
There are 2 main processes that generate
variation:

Mutation
Recombination
2

Mutation and Recombination

Mutation is a change in the genetic

information
Recombination is a different arrangement of
the same genetic material
The cat sat on the mat (1)
The bat sat on the hat mutation (2)
The cat sat on the hat recombination of 1
and 2

The main properties of DNA

The genetic material must be able to:

Store information
Replicate (when cells divide)
Express information (as proteins)
Mutate at a low frequency (less than 1 in a
million)

DNA is a molecule that is very well

suited to doing all 4 of these

Mutation
Can occur in any cell at any time, cause may be:

Internal (e.g. mistakes during replication of DNA)

External (e.g. radiation, chemicals)
Most mutations have no effect (neutral)
A few mutations are harmful
A very few mutations are beneficial
Only harmful and beneficial mutations are acted on
by natural selection
Mutations may be non-coding (not in part of gene that
codes for protein - have no effect, or affect gene
expression) or coding.

Effects of coding mutations

Synonymous: the cat ate the rat
Missense:

the fat ate the rat

Nonsense:
the cat ate the
Frameshift:
the cax tat eth era t
Synonymous has no effect on protein,
nonsense makes a smaller protein,
missense/frameshift make incorrect
protein

Conditional mutations
The effects of many coding

mutations depend on
environmental factors
Siamese cats have mutation
in enzyme for black pigment
production, that stops it
working at normal body
temperature
Cooler parts of cat are dark
because enzyme OK at
lower temperature

Mutation during DNA

replication
Replication of DNA is not perfectly accurate, but

there are several ways to correct the mistakes

ACGTACGTAACGTG...
TGCATGCATTGAACGGT
DNA polymerase makes about 1 mistake per 105 bp.
DNA polymerase has a proof-reading activity to correct its
own mistakes (99%).
After DNA replication there is a mismatch repair system to
correct remaining mistakes (99.9%).
This leaves an overall error rate of about 1 base in 1010.

Error correction in
DNA replication
Overall error rate is

about 10-10 per

division
About 1 mistake per
cell per division in
humans

Mutation due to environmental factors

Mutations may be caused by chemicals or

radiation
Chemicals (mutagens) may disrupt
hydrogen bonds between bases, by modifying
them or getting between them
Radiation (including ultra-violet and
radioactive emissions) can damage structure
of bases
These agents may be natural or man-made

DNA excision repair

Another system to repair mutated or

damaged DNA
a
g
a
g

Mutated DNA
One strand is nicked

DNA removed between nicks

a
t

Correct DNA is synthesised

Mendels experiments
Gregor Mendel (a 19th century Czech monk)

worked out the basic laws of genetic

inheritance by breeding pea plants
He chose simple characteristics that are
determined by single genes (monogenic)
Many characters such as height, IQ, disease
susceptibility are determined by several
genes (polygenic)

Mendels first cross

P1 (parental) generation: wrinkled seeds
crossed with smooth seeds
F1 generation: all smooth seeds. Crossed
with itself...

F2 generation: smooth and wrinkled

in ratio 3:1

Mendels genetic hypothesis

AA

aa
A

A
A

Genes come in pairs. Each of the parents has

2 copies of this gene. The A form gives smooth
seeds, the a form gives wrinkled.

Parents produce gametes (eggs, sperm, pollen)

which have 1 copy of the gene.

Aa

Fertilisation produces the F1 generation, all smooth

because the A form is dominant over a;
a is recessive
Each F1 plant produces equal numbers of A and a
gametes which fertilise at random to produce the F2
plants. 1/4 of them are AA (smooth), 1/2 are Aa
(smooth) and 1/4 are aa (wrinkled).

Cross with two genes

AABB

AB

aabb

Ab

aB

ab

AB
AB

ab
AaBb

AB Ab aB ab
4 types of gametes
in equal numbers

Ab
aB
ab
9/16 yellow/smooth
3/16 green/smooth
3/16 yellow/wrinkled
1/16 green/wrinkled

Summary of Mendels
experiments

Genes in an organism come in pairs

Some forms (alleles) of a gene are dominant over

other alleles which are recessive

One (at random) of each pair of genes goes into a
gamete (segregation)
Gametes meet randomly and fertilise
The numbers and types of offspring in a cross are
determined by the above laws
Separate genes behave independently of each other
(later, exceptions to this rule were found)

Genes and chromosomes

Genes can have several different forms due to

mutations in DNA sequence. These forms are called

alleles. Property of having different forms is called
polymorphism
Normal human body cells (somatic cells) are
diploid: 23 pairs of chromosomes:

Numbers 1-22 (autosomes)

X and Y (sex chromosomes)
XX in females, XY in males

Gametes (eggs, sperm, pollen) are haploid, i.e. they

have a single copy of each chromosome

Phenotype, Genotype, Alleles

The phenotype of an organism is its

observable properties
The genotype is the set of alleles it
has for all of its genes (5,000 in
bacteria; 35,000 in humans)
New alleles are created by mutation
and their effect the phenotype may be
dominant or recessive

Significance of genetic
variation
Some alleles directly cause specific traits,

such as (in humans) rare genetic diseases

e.g. Cystic fibrosis, sickle-cell anaemia; (in
bacteria) ability to grow on certain sugars
Many alleles contribute to many traits of an
organism such as size, shape, intelligence,
behaviour, and risk of getting diseases e.g. (in
humans) cancer, heart disease, asthma
Genetic variation is what evolution acts on.
Without it there would be no different species.

Multiple genes and quantitative traits

bell-shaped (normal) distribution in
population
These are influenced by several
genes, so the overall effect
depends on the random selection
of alleles in an individual
e.g. for height genes, you are
more likely to have a mixture of tall
and short alleles than all tall or all
short

number

Many traits like height, IQ show a

height

Genetic Linkage and

Recombination

Mendel was lucky - the genes he chose all

segregated independently
This is not true of all genes - many genes are linked
In humans, there are 23 pairs of chromosomes and
about 35000 pairs of genes - each chromosome has a
few hundred to a few thousand genes
Genes close together on the same chromosome are
linked and do not segregate independently

Terms & Definitions

Genes can have several different forms due to

mutations in the DNA. These forms are called alleles.

Property of having different forms is called
polymorphism
Organism with 2 copies of the same allele of a gene
in diploid cells is homozygous for the gene
Organism with different alleles of a gene in diploid
cells is heterozygous for the gene
Males are hemizygous for genes on X and Y
chromosomes

Modes of inheritance
Dominant alleles affect the phenotype when

present in 1 copy (heterozygous), e.g.

Huntingtons disease
Recessive alleles affect the phenotype only
when present in 2 copies (homozygous), e.g.
cystic fibrosis
Can tell whether dominant or recessive by
studying Mode of Inheritance in families

Autosomal dominant
inheritance
Person with trait in each generation
Males and females equally likely
to show trait
Where 1 parent is heterozygous,
about 50% of offspring show trait
Example: Huntingtons disease

Autosomal recessive
inheritance

Trait may skip generations

Males and females equally likely to show trait
Heterozygotes (carriers) do not show trait
About 25% of offspring of 2 carriers will show trait
Example: cystic fibrosis

X-linked recessive inheritance

Carrier (heterozygous,
unaffected) mothers pass the trait
to about 50% of sons

Trait is never transmitted

from father to son

In the population, trait will be much more common in males

than females. Example: muscular dystrophy

Jumping genes
Genomes are not always stable. Some DNA sequences can

jump from one place to another (transposons)

Transposons can be responsible for things like antibiotic
resistance in bacteria
They can also affect the expression of a gene near to where they
jump
If a transposon jumps in some cells but not others, can get a
variegated phenotype

Maize (corn) cob

Transposon mechanism

Oogenesis & spermatogenesis

(animals)
Oogenesis is the process of egg formation
Spermatogenesis is the process of sperm

formation
Both go through several stages, with (in
mammals) different timing in males than
females
Sperms go through more cell divisions than
eggs do - more chance of mutation

Fertilisation
2 haploid cells (egg, sperm) form 1 diploid cell

(the zygote) which develops into the embryo

Whether sperm contained an X or Y
chromosome determines if embryo is female or
male
Embryo contains an assortment of genes from
each original parent - more genetic diversity
Mitochondria (and their DNA) come only from
mother via the egg - maternal inheritance

Meiosis
Process of cell division in germ cells,

to produce eggs or sperm (gametes)

1 diploid cell
2 haploid cells
Goes through several defined stages
Chromosomes are passed on as rearranged copies due to recombination
- creates genetic diversity

Meiosis and Recombination

Chromosomes pair up

DNA replication
Chiasmata form

Recombination

1st cell division

Gametes

2nd cell division

Result: meiosis generates new combinations of alleles

The overall process

Mum

Egg

Dad

Sperm

Development
to adult
Fertilisation

Meiosis
Recombination

How much genetic variation?

About 35,000 genes in humans
If each gene has only 2 alleles (probably

an underestimate), then:

Number of possible genotypes = 335,000 =

1016,700

Far more than all the atoms in the

Universe!
Essentially, we are all genetically unique
(except identical twins)

Recombination
The closer together 2 genes are on the same

chromosome, the less likely there is to be a

recombination between them - such genes are
linked and do not segregate independently
Genes that are far apart are likely to have a
recombination between them and will segregate
independently - such genes are unlinked
Genes on separate chromosomes are unlinked

Linkage to an autosomal
dominant gene
AA
aa

Aa

A and a are alleles of a marker

gene

Aa

Yellow shading indicates affected

with a genetic disease (NOT caused
by gene A/a)

Aa

aa

Aa

aa

Allele a of the marker gene

always segregates with the disease,
so the 2 genes must be linked

An application of linkage
Can do prenatal

diagnosis for
genetic disease
using a linked
bb
gene
Useful when you
dont know
exactly what
Bb
gene is causing
the disease

BB

bb
Bb

?
bb