Genes in Populations Revision Notes
Lecture 1 – Background and structure
Population genetics: The study of genetic variation in populations.
- Any organism
- Any population: Natural, artificial, experimental
- Any environment: Soil, aquatic, terrestrial
- If there wasn’t any variation, our population would quickly become extinct.
Why do we study population genetics?
1. Understand how natural selection operates
2. Understand the basis of genetic disease
3. Understand human origins and evolution
4. Help conservation biology
5. Forensic science
6. Agricultural improvement
Inheritance – a historical perspective:
- Offspring resemble their parents.
- Heritable variation is necessary for evolutionary change.
- No variation leads to extinction.
- How does resemblance occur?
Early ideas – the peculiar cause of George Spencer: 1941 hanged for committing bestiality (sow was also killed)
“fathered” a deformed piglet.
The first theory of inheritance: Jean-Baptiste de Lamarck (1744-1829)
- Inheritance of acquired characteristics
- Organs that are used grow bigger and offspring inherit these characters – wrong
- Epigenetics can explain some of his ideas
- Darwin didn’t know how inheritance happened
Mendel and Inheritance (1822-1884):
- Father of genetics
- Classic experiments on peas (around 1865)
- Results weren’t known to Darwin
- Experiments rediscovered in 1900
Other population genetics landmarks:
1900: Mendel’s laws rediscovered
1907: Hardy and Weinberg independently work out genotype frequencies
1909: Terms “gene”, “genotype” and “phenotype” invented by Johasen
1911: Morgan and co-workers discover linkage. First genetic map built
1918: Fisher resolved Mendelians vs Biometricians debate
1953: Watson and Crick discover structure of DNA
1977: DNA sequencing invented by Sanger
2003: Human genome sequenced
TODAY: Over 5 million known positions in the human genome
Lecture 2 – Mutation, variation and genome organisation
What are mutations?
- The failure to store genetic information faithfully.
- Daughter cell division can cause problems but also parent offspring.
- Can affect whole chromosomes or a single gene and can be spontaneous or induced.
1
,- In the lab we can induce a mutation in a gene and use this to determine its role.
- Can be harmful, neutral or beneficial.
- Are the source of all genetic variation and are necessary for natural selection and evolution.
Causes of mutation:
- Induced mutations – radiation, UV, X-rays.
- Mutagen: Anything that increases chemical reactivity in cells.
- Chernobyl (1986) “restored Eden”
- Fukushima (2011):
Mutation rate went up, lower population size in hotspots.
Spider web pattern – slightly off, indicates a hotspot. Beetles – unequal/messed up marking pattern indicates a
hotspot.
Chromosomes and karotypes:
- Human chromosomes are present in pairs – diploid. 23 pairs, 2n = 46
- Gametic cells (eggs and sperm) are haploid.
- Karotype: The number and appearance of chromosomes in the nucleus of a eukaryotic cell.
Used to describe the complete set of chromosomes in a species of in an individual organism.
- Chromosomal variation:
1. Polyploidy: Multiple chromosomes
2. Aneuploidy: Wrong number of chromosomes
3. Translocations: Exchange of parts between non-homologous chromosomes
4. Deletions: Certain elements are deleted
5. Inversions: When certain regions of the gene are inverted
Polyploidy:
- Humans (and most vertebrates) are diploid – two complete sets of chromosomes.
- More than two sets (dispermy), results in three complete sets of chromosomes (3n = 69).
- Happens in 1-3% of conceptions – always lethal.
- Polyploidy in higher plants is common. Related species often vary in ploidy – chrysanthemums.
- Bacteria are usually monoploid – one set of chromosomes.
Aneuploidy:
- When one set of chromosomes is incomplete (e.g. a chromosome missing, an extra chromosome is present).
- Autosomes:
1. Nullisomy: Both members of a pair are missing (lethal).
2. Monosomy: One member of a pair is missing (lethal).
3. Trisomy: One extra chromosome (usually lethal).
4. Trisomy 21: Down’s Syndrome (not lethal – longevity: 40 years +).
- Sex chromosomes:
Lacking a chromosome:
45X – Turner’s Syndrome (infertile – no other effects, worse for males)
45Y – Inviable
Extra chromosomes:
47XYY 47XXY 47XXX
Minor effects
Extra sex chromosomes don’t seem to cause too many issues
Translocations:
- Exchange of parts between non-homologous chromosomes.
- Carriers are normal.
- Offspring can have the wrong number of copies of each chromosome – usually lethal.
2
, Deletions:
- Part of a chromosome is missing.
- Patient only has one copy of each gene in that region.
- Severity depends upon the size of the missing region.
- Chromosome 5 – Cri-du-chat syndrome (also causes developmental issues).
Inversions:
- When certain regions of the gene are inverted: DEFG GFED.
- Usually fine because genes are still present and functional – problem if the region is lost.
- Paracentric: Centromere excluded.
- Pericentric: Includes centromere.
- Often no effect on phenotype – a balanced rearrangement.
- Possible problems in meiosis.
Crick’s second great discovery – the genetic code:
- Three nucleotides are called a codon. Every codon specifies an amino acid.
- An amino acid can be encoded by more than one codon – the code is degenerate.
- 1.5% encodes proteins
- 3% regulates protein expression
- 45% caused by transposons – variable/moveable positions of DNA
- 6.6% not transcribed
- 44% contains many useful variations
DNA mutations:
- Coding region mutations: Substitutions, insertions and deletions.
- Non-coding region mutations: Repeat length variation and useful genetic markers.
1. Substitutions: Substitution of a nucleotide.
- Silent/synonymous mutation: Codes for the same amino acid.
- Replacement/non-synonymous mutation: Codes for a different amino acid. May not code for the same protein.
2. Insertion/deletions (indels):
- Nucleotide base deleted, shift position.
- Nucleotide base inserted, shift position.
- Different protein encoded due to shift in the open reading frame – coding region.
- Genotype change can influence phenotype (albinism, pea colour, sickle cell anaemia, bananaquits).
Non-coding region mutations:
- 95% of the genome isn’t involved in protein coding/expression.
- Variation in these parts of the genome is very useful.
- SNPs single nucleotide polymorphisms: 12,000,000 discovered in man (0.3% of the genome).
- Satellite DNA: Units of repeated DNA.
- Microsatellites/simple tandem repeats.
- Nearly always harmless.
- Widely used in: Finding disease genes, conservation genetics, evolutionary genetics, agricultural improvement.
Gametic Somatic
Heritable Yes No
Effect Can be severe Usually mild
Affects all cells Yes No
Summary:
- Genetic variation is caused by mutation.
- Without mutation there would be no evolution.
- Mutations can affect chromosomes or nucleotides.
3
Lecture 1 – Background and structure
Population genetics: The study of genetic variation in populations.
- Any organism
- Any population: Natural, artificial, experimental
- Any environment: Soil, aquatic, terrestrial
- If there wasn’t any variation, our population would quickly become extinct.
Why do we study population genetics?
1. Understand how natural selection operates
2. Understand the basis of genetic disease
3. Understand human origins and evolution
4. Help conservation biology
5. Forensic science
6. Agricultural improvement
Inheritance – a historical perspective:
- Offspring resemble their parents.
- Heritable variation is necessary for evolutionary change.
- No variation leads to extinction.
- How does resemblance occur?
Early ideas – the peculiar cause of George Spencer: 1941 hanged for committing bestiality (sow was also killed)
“fathered” a deformed piglet.
The first theory of inheritance: Jean-Baptiste de Lamarck (1744-1829)
- Inheritance of acquired characteristics
- Organs that are used grow bigger and offspring inherit these characters – wrong
- Epigenetics can explain some of his ideas
- Darwin didn’t know how inheritance happened
Mendel and Inheritance (1822-1884):
- Father of genetics
- Classic experiments on peas (around 1865)
- Results weren’t known to Darwin
- Experiments rediscovered in 1900
Other population genetics landmarks:
1900: Mendel’s laws rediscovered
1907: Hardy and Weinberg independently work out genotype frequencies
1909: Terms “gene”, “genotype” and “phenotype” invented by Johasen
1911: Morgan and co-workers discover linkage. First genetic map built
1918: Fisher resolved Mendelians vs Biometricians debate
1953: Watson and Crick discover structure of DNA
1977: DNA sequencing invented by Sanger
2003: Human genome sequenced
TODAY: Over 5 million known positions in the human genome
Lecture 2 – Mutation, variation and genome organisation
What are mutations?
- The failure to store genetic information faithfully.
- Daughter cell division can cause problems but also parent offspring.
- Can affect whole chromosomes or a single gene and can be spontaneous or induced.
1
,- In the lab we can induce a mutation in a gene and use this to determine its role.
- Can be harmful, neutral or beneficial.
- Are the source of all genetic variation and are necessary for natural selection and evolution.
Causes of mutation:
- Induced mutations – radiation, UV, X-rays.
- Mutagen: Anything that increases chemical reactivity in cells.
- Chernobyl (1986) “restored Eden”
- Fukushima (2011):
Mutation rate went up, lower population size in hotspots.
Spider web pattern – slightly off, indicates a hotspot. Beetles – unequal/messed up marking pattern indicates a
hotspot.
Chromosomes and karotypes:
- Human chromosomes are present in pairs – diploid. 23 pairs, 2n = 46
- Gametic cells (eggs and sperm) are haploid.
- Karotype: The number and appearance of chromosomes in the nucleus of a eukaryotic cell.
Used to describe the complete set of chromosomes in a species of in an individual organism.
- Chromosomal variation:
1. Polyploidy: Multiple chromosomes
2. Aneuploidy: Wrong number of chromosomes
3. Translocations: Exchange of parts between non-homologous chromosomes
4. Deletions: Certain elements are deleted
5. Inversions: When certain regions of the gene are inverted
Polyploidy:
- Humans (and most vertebrates) are diploid – two complete sets of chromosomes.
- More than two sets (dispermy), results in three complete sets of chromosomes (3n = 69).
- Happens in 1-3% of conceptions – always lethal.
- Polyploidy in higher plants is common. Related species often vary in ploidy – chrysanthemums.
- Bacteria are usually monoploid – one set of chromosomes.
Aneuploidy:
- When one set of chromosomes is incomplete (e.g. a chromosome missing, an extra chromosome is present).
- Autosomes:
1. Nullisomy: Both members of a pair are missing (lethal).
2. Monosomy: One member of a pair is missing (lethal).
3. Trisomy: One extra chromosome (usually lethal).
4. Trisomy 21: Down’s Syndrome (not lethal – longevity: 40 years +).
- Sex chromosomes:
Lacking a chromosome:
45X – Turner’s Syndrome (infertile – no other effects, worse for males)
45Y – Inviable
Extra chromosomes:
47XYY 47XXY 47XXX
Minor effects
Extra sex chromosomes don’t seem to cause too many issues
Translocations:
- Exchange of parts between non-homologous chromosomes.
- Carriers are normal.
- Offspring can have the wrong number of copies of each chromosome – usually lethal.
2
, Deletions:
- Part of a chromosome is missing.
- Patient only has one copy of each gene in that region.
- Severity depends upon the size of the missing region.
- Chromosome 5 – Cri-du-chat syndrome (also causes developmental issues).
Inversions:
- When certain regions of the gene are inverted: DEFG GFED.
- Usually fine because genes are still present and functional – problem if the region is lost.
- Paracentric: Centromere excluded.
- Pericentric: Includes centromere.
- Often no effect on phenotype – a balanced rearrangement.
- Possible problems in meiosis.
Crick’s second great discovery – the genetic code:
- Three nucleotides are called a codon. Every codon specifies an amino acid.
- An amino acid can be encoded by more than one codon – the code is degenerate.
- 1.5% encodes proteins
- 3% regulates protein expression
- 45% caused by transposons – variable/moveable positions of DNA
- 6.6% not transcribed
- 44% contains many useful variations
DNA mutations:
- Coding region mutations: Substitutions, insertions and deletions.
- Non-coding region mutations: Repeat length variation and useful genetic markers.
1. Substitutions: Substitution of a nucleotide.
- Silent/synonymous mutation: Codes for the same amino acid.
- Replacement/non-synonymous mutation: Codes for a different amino acid. May not code for the same protein.
2. Insertion/deletions (indels):
- Nucleotide base deleted, shift position.
- Nucleotide base inserted, shift position.
- Different protein encoded due to shift in the open reading frame – coding region.
- Genotype change can influence phenotype (albinism, pea colour, sickle cell anaemia, bananaquits).
Non-coding region mutations:
- 95% of the genome isn’t involved in protein coding/expression.
- Variation in these parts of the genome is very useful.
- SNPs single nucleotide polymorphisms: 12,000,000 discovered in man (0.3% of the genome).
- Satellite DNA: Units of repeated DNA.
- Microsatellites/simple tandem repeats.
- Nearly always harmless.
- Widely used in: Finding disease genes, conservation genetics, evolutionary genetics, agricultural improvement.
Gametic Somatic
Heritable Yes No
Effect Can be severe Usually mild
Affects all cells Yes No
Summary:
- Genetic variation is caused by mutation.
- Without mutation there would be no evolution.
- Mutations can affect chromosomes or nucleotides.
3
