1. Genetic Variation
Chapter 10 and 11 in the course textbook especially pages , ,

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

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 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. Mendel’s 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. Mendel’s 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

13. Mendel’s 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 Aa
Fertilisation produces the F1 generation, all smooth
because the “A” form is dominant over “a”;
“a” is recessive A a
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 AaBb AB Ab aB ab AB Ab 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 Mendel’s 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. Huntington’s 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: Huntington’s 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