Transcript 1st

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 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
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 seeds
crossed with smooth seeds
F1 generation: all smooth seeds. Crossed
with itself………...
F2 generation: smooth and wrinkled
in ratio 3:1
Mendel’s genetic hypothesis
AA
aa
A
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.
a
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
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).
Cross with two genes
AABB
AB
aabb
Ab
aB
ab
AB
AB
ab
Ab
AaBb
AB Ab aB ab
4 types of gametes
in equal numbers
aB
ab
9/16 yellow/smooth
3/16 green/smooth
3/16 yellow/wrinkled
1/16 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 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