Genetic Variation

1
Genetic Variation

• Chapter 10 and 11 in the course textbook
  especially pages 187-197, 227-228, 250-255

2
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

3
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

4
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

5
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.

6
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

7
(No Transcript)
8
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.
9
Error correction in DNA replication

• Overall error rate is about 10-10 per division
• About 1 mistake per cell per division in humans

10
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

11
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)

12
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 31
13
Mendels genetic hypothesis
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.
AA
aa
Parents produce gametes (eggs, sperm,
pollen) which have 1 copy of the gene.
A
a
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).
14
Cross with two genes
AABB
aabb
AB
ab
AaBb
AB
ab
aB
Ab
4 types of gametes in equal numbers
9/16 yellow/smooth 3/16 green/smooth 3/16
yellow/wrinkled 1/16 green/wrinkled
15
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)

16
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

17
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

18
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

19
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
20
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

21
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