Genetic Variation

Chapter 10 and 11 in the course textbook especially pages 187-197,

227-228, 250-255

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

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

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 itsown mistakes (99%).After DNA replication there is a “mismatch repair” system tocorrect 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

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)

Mendel’s first cross

P1 (parental) generation: wrinkled seedscrossed with smooth seeds

F1 generation: all smooth seeds. Crossedwith itself………...

F2 generation: smooth and wrinkled in ratio 3:1

Mendel’s genetic hypothesis

Aa

AA aa

A a

A a

A

a

Genes come in pairs. Each of the parents has2 copies of this gene. The “A” form gives smoothseeds, the “a” form gives wrinkled.

Parents produce gametes (eggs, sperm, pollen)which have 1 copy of the gene.

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 F2plants. 1/4 of them are AA (smooth), 1/2 are Aa(smooth) and 1/4 are aa (wrinkled).

Cross with two genes

AB ab

AABB aabb

AaBb

AB abaBAb

4 types of gametesin equal numbers

AB Ab aB ab

AB

Ab

aB

ab

9/16 yellow/smooth3/16 green/smooth3/16 yellow/wrinkled1/16 green/wrinkled

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)

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

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

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

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 traitto about 50% of sons

Trait is never transmittedfrom father to son

In the population, trait will be much more common in malesthan females. Example: muscular dystrophy