Genetica m.i.v. populatiegenetica
Chapter 1: The genetics revolution
1.1. The birth of genetics
Brief history: like begets like
- “De appel valt niet ver van de boom”: children resemble their parents,
- used to domesticate animals and selective breeding
o Mechanism behind this was unknown
o Different religious/philosophic explanations
Lamarckism
- Named after Lamarck, organisms acquired
characteristics from parents to offspring
- Inheritance of acquired characteristics
- This is not how inheritance generally works
- However:
o Cultural inheritance is important in some species (e.g. humans, songbirds)
o Epigenetic inheritance does exist (e.g. DNA methylation can be modified by
environment)
Traits are inherited because they have a genetic basis
- Every kind of characteristic is a trait
- Darwin had a good understanding of the process of evolution, but not about the mechanism
of inheritance (genetics)
- Darwin believed in pangenesis – a form of blending inheritance
o Information of mother and father is blended and you get a mixed form
- Why blending inheritance does not work:
o Blending inheritance = mixing of parent’s characteristics
o Under blending inheritance, variation should be eventually lost
Pure colours cannot be recreated from mixture
o Gregor Mendel showed inheritance of discrete characters (no blending)
The colours did not get lost
Mendel’s work was not known to Darwin and his colleagues
Early 20th century: biometricians vs. Mendelians
- Biometricians: - Mendelians:
o Variation is continuous o Variation is discrete
o Evolution is gradual process o Follows Mendel’s laws
o Blending inheritance o Evolution can make jumps
1
,The birth of Genetics
- Gregor Mendel:
o Hybridisation experiments with pea plants
- Cross plants with purple x white flowers
o Under blending inheritance, you might expect all offspring to have intermediate
colour
o All offspring were purple (genetic mechanism called dominance, for other traits,
offspring can look intermediate)
o However, the real proof against blending inheritance comes in the next generation
Because intermediate colours does exist in nature
o Selfing the first generation, produced
705 with purple flowers
224 with white flowers
(Mendel kept good notice of everything, this is important for a scientist)
=> 3:1 ratio (3/4 purple, ¼ white)
The reappearance of white flowers in the second offspring generation
contradicts blending inheritance
Genetic inheritance
- Each individual has two copies of a gene in somatic cells (=body
cells)
o Called a diploid organism* (2n)
o Exceptions: e.g. ants and bees are haplodiploid, gametes are
haploid, breadwheat is hexaploidy, …
- Only one (random) copy enters gametes (=eggs and sperm)
- Egg and sperm copies are combined to form new diploid individual
- The gene for flower colour has two alleles (=variants of a gene)
o The purple allele is dominant
o The white allele is recessive
o And the end of the course you will be able to calculate the
chance of…
But what about continuous traits?
- How can the continuous variation in some traits be explained by mendelian inheritance?
- Continuous traits often show normal (Gaussian) distributions in natural populations. Why?
o The central limit theorem: normal distributions as the natural consequence of
combining many small effects
o in biology you can explain this in very obliquitous way
- Modern Evolutionary synthesis:
o 1918 RA fisher reconciled mendelian inheritance with continuous trait variation
o Infinitesimal model: (can combine the two)
Some traits are influenced by many genes of small effect (“polygenic”)
This leads to continuous trait variation (comes close to normal distribution)
o E.g. of three genes that control the colour of the flower
2
, A/a and B/b and C/c
Dark red: AABBCC
White: aabbcc
Intermediate: AaBbCc
Next generation: relative proportions of each of the
combinations form a normal distribution
- The fact that there is a normal distribution doesn’t prove this is
genetically inherited!
- 1 gene is Mendelian inheritance, many genes is polygenetic
inheritance
Key events in the history of genetics
- 1941: one-gene-one enzyme hypothesis:
o Genes control traits by encoding for enzymes
- 1953: molecular structure of DNA
o Double helix with base pairs between nucleotides of both strands
o A-T and G-C
- 1961: gene regulation
o Regulatory elements control gene expression
o The way an organism looks like is not only controlled by their genes but also how
these genes are regulated
- 1967: translation
o Set of three nucleotides (codon) encodes for one amino acid
o Messenger RNA (mRNA) carries information from DNA to ribosome
o DNA replicates:
DNA is copied after cell division
DNA is inherited from parent to offspring
o DNA is transcribed into RNA
o RNA is translated into proteins
1.2. After cracking the code
- Model organisms (e.g. Drosophila, Arabidopsis thaliana, Bacilla subtilis, E. coli, …)
o Characteristics:
Small and easy to keep
Short generation time
Small genome
Large numbers of offspring
o Idea is that what is learned from one organism holds true for others
- See Griffiths page 713
1.3. Genetics today
- More about understanding the mechanisms and problems, not the specific details from
these examples
Example I: Medical genetics
3
, - Louise Benge has a severe calcification in het arterial
- What do these facts tell us:
o Benge’s brothers and sisters also developed arterial calcification > genetic basis/
disease
o Parents were unaffected > recessive (parents heterozygote)
o Very low level of an enzyme called CD73 (sends a signal that blocks calcification) >
production of this enzyme is inhibited, something can be wrong with the regulation of
the gene that codes for this enzyme
- How to search for the disease allele?
o Tracing a disease gene through a family tree
Circles females, squares males, colour means
they carry the disease
Parents where related to each other (third
cousins), common in genetic diseases
Probability of 2 individuals that hare
heterozygous is rare but not if they are related
o DNA sequences of unrelated individuals will have
differences every few 100 base pairs
o The researchers identified chromosomal segments for which both parents and
Benge and all her siblings were identical CD73 gene
- DNA sequencing identified the gene defect
o Truncated protein
- Knowing the defect allowed to develop a medication
- Substitute for CD73 in signalling cells to keep the calcification pathway turned off
Colour blindness
- Can be corrected trough gene therapy
- Three opsin genes
o Blue
o Green
o Red
- More red-green colour blindness in men
o Red en green opsin genes are on X chromosome
o Men only have 1 copy of the X chromosome
Genetic variation
- Single nucleotide polymorphisms (SNPs)
o Most common type of genetic variation
o Difference of one basepair between two copies
- Mutations: (origin of genetic variation)
o Point mutation = change of one base in the DNA
o A point mutation creates a single nucleotide polymorphism (SNP)
4
Chapter 1: The genetics revolution
1.1. The birth of genetics
Brief history: like begets like
- “De appel valt niet ver van de boom”: children resemble their parents,
- used to domesticate animals and selective breeding
o Mechanism behind this was unknown
o Different religious/philosophic explanations
Lamarckism
- Named after Lamarck, organisms acquired
characteristics from parents to offspring
- Inheritance of acquired characteristics
- This is not how inheritance generally works
- However:
o Cultural inheritance is important in some species (e.g. humans, songbirds)
o Epigenetic inheritance does exist (e.g. DNA methylation can be modified by
environment)
Traits are inherited because they have a genetic basis
- Every kind of characteristic is a trait
- Darwin had a good understanding of the process of evolution, but not about the mechanism
of inheritance (genetics)
- Darwin believed in pangenesis – a form of blending inheritance
o Information of mother and father is blended and you get a mixed form
- Why blending inheritance does not work:
o Blending inheritance = mixing of parent’s characteristics
o Under blending inheritance, variation should be eventually lost
Pure colours cannot be recreated from mixture
o Gregor Mendel showed inheritance of discrete characters (no blending)
The colours did not get lost
Mendel’s work was not known to Darwin and his colleagues
Early 20th century: biometricians vs. Mendelians
- Biometricians: - Mendelians:
o Variation is continuous o Variation is discrete
o Evolution is gradual process o Follows Mendel’s laws
o Blending inheritance o Evolution can make jumps
1
,The birth of Genetics
- Gregor Mendel:
o Hybridisation experiments with pea plants
- Cross plants with purple x white flowers
o Under blending inheritance, you might expect all offspring to have intermediate
colour
o All offspring were purple (genetic mechanism called dominance, for other traits,
offspring can look intermediate)
o However, the real proof against blending inheritance comes in the next generation
Because intermediate colours does exist in nature
o Selfing the first generation, produced
705 with purple flowers
224 with white flowers
(Mendel kept good notice of everything, this is important for a scientist)
=> 3:1 ratio (3/4 purple, ¼ white)
The reappearance of white flowers in the second offspring generation
contradicts blending inheritance
Genetic inheritance
- Each individual has two copies of a gene in somatic cells (=body
cells)
o Called a diploid organism* (2n)
o Exceptions: e.g. ants and bees are haplodiploid, gametes are
haploid, breadwheat is hexaploidy, …
- Only one (random) copy enters gametes (=eggs and sperm)
- Egg and sperm copies are combined to form new diploid individual
- The gene for flower colour has two alleles (=variants of a gene)
o The purple allele is dominant
o The white allele is recessive
o And the end of the course you will be able to calculate the
chance of…
But what about continuous traits?
- How can the continuous variation in some traits be explained by mendelian inheritance?
- Continuous traits often show normal (Gaussian) distributions in natural populations. Why?
o The central limit theorem: normal distributions as the natural consequence of
combining many small effects
o in biology you can explain this in very obliquitous way
- Modern Evolutionary synthesis:
o 1918 RA fisher reconciled mendelian inheritance with continuous trait variation
o Infinitesimal model: (can combine the two)
Some traits are influenced by many genes of small effect (“polygenic”)
This leads to continuous trait variation (comes close to normal distribution)
o E.g. of three genes that control the colour of the flower
2
, A/a and B/b and C/c
Dark red: AABBCC
White: aabbcc
Intermediate: AaBbCc
Next generation: relative proportions of each of the
combinations form a normal distribution
- The fact that there is a normal distribution doesn’t prove this is
genetically inherited!
- 1 gene is Mendelian inheritance, many genes is polygenetic
inheritance
Key events in the history of genetics
- 1941: one-gene-one enzyme hypothesis:
o Genes control traits by encoding for enzymes
- 1953: molecular structure of DNA
o Double helix with base pairs between nucleotides of both strands
o A-T and G-C
- 1961: gene regulation
o Regulatory elements control gene expression
o The way an organism looks like is not only controlled by their genes but also how
these genes are regulated
- 1967: translation
o Set of three nucleotides (codon) encodes for one amino acid
o Messenger RNA (mRNA) carries information from DNA to ribosome
o DNA replicates:
DNA is copied after cell division
DNA is inherited from parent to offspring
o DNA is transcribed into RNA
o RNA is translated into proteins
1.2. After cracking the code
- Model organisms (e.g. Drosophila, Arabidopsis thaliana, Bacilla subtilis, E. coli, …)
o Characteristics:
Small and easy to keep
Short generation time
Small genome
Large numbers of offspring
o Idea is that what is learned from one organism holds true for others
- See Griffiths page 713
1.3. Genetics today
- More about understanding the mechanisms and problems, not the specific details from
these examples
Example I: Medical genetics
3
, - Louise Benge has a severe calcification in het arterial
- What do these facts tell us:
o Benge’s brothers and sisters also developed arterial calcification > genetic basis/
disease
o Parents were unaffected > recessive (parents heterozygote)
o Very low level of an enzyme called CD73 (sends a signal that blocks calcification) >
production of this enzyme is inhibited, something can be wrong with the regulation of
the gene that codes for this enzyme
- How to search for the disease allele?
o Tracing a disease gene through a family tree
Circles females, squares males, colour means
they carry the disease
Parents where related to each other (third
cousins), common in genetic diseases
Probability of 2 individuals that hare
heterozygous is rare but not if they are related
o DNA sequences of unrelated individuals will have
differences every few 100 base pairs
o The researchers identified chromosomal segments for which both parents and
Benge and all her siblings were identical CD73 gene
- DNA sequencing identified the gene defect
o Truncated protein
- Knowing the defect allowed to develop a medication
- Substitute for CD73 in signalling cells to keep the calcification pathway turned off
Colour blindness
- Can be corrected trough gene therapy
- Three opsin genes
o Blue
o Green
o Red
- More red-green colour blindness in men
o Red en green opsin genes are on X chromosome
o Men only have 1 copy of the X chromosome
Genetic variation
- Single nucleotide polymorphisms (SNPs)
o Most common type of genetic variation
o Difference of one basepair between two copies
- Mutations: (origin of genetic variation)
o Point mutation = change of one base in the DNA
o A point mutation creates a single nucleotide polymorphism (SNP)
4
