Samenvatting partim population genetics

Genetica m.i.v. populatiegenetica
Population genetics
Mutation, variation and selection
Chapter 4 of Futuyma and Kirkpatrick.
Ingredients to the evolutionary process
- Variation in traits (phenotypes, characteristics)
- Reproduction with inheritance of traits
- Variation in reproductive output among individuals
- → Abundance of different trait values will change
o Natural selection
o Random changes (more/less reproduction and survival by chance; genetic drift)
- → Genetic differences determine differences in phenotypes (appearance)


Genetic variation is the fundamental currency of evolution
- Genetic pathways work also if there is no variation
- But,
o We use variation to study genetics (see all previous lectures!)
o Evolution only happens if there is variation
- Population genetics describes genetic variation within and among populations and its
change over time
- Population genetics is roughly the same as evolutionary genetics within species ("Micro-
evolution")


Origins of genetic variation: mutation
- Mutations: Errors during replication of DNA
- Without these errors, no variation
- Types of mutation:
o Point mutation A → T, C → T etc.
 Single DNA base (pair) is changed
 Results in single nucleotide polymorphism (SNP)
 De novo mutation is a variation which exists in offspring but not in the parents
o Structural mutation
 Affect more than one base pair (bp)
 Can be a few bp to millions of bp long
 Chromosome fissions and fusions lead to very
different chromosome numbers across species
- Types of DNA variants:
o Single nucleotide polymorphisms (SNPs)
 A→C
o Insertions
 ACTT → ACGCATT
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, o Deletions
 ACGCATT → ACTT
o Inversions
 ACGCATT → ACACGTT
o Duplications
 ACGCATT → ACGCAGCATT
 Gene duplications can allow one copy to evolve a new function
- Whole genome duplication (most extreme structural mutation)
o In rare cases, gametes remain diploid during meiosis
o If two such gametes mate, this can result in individuals with 4 copies of each
chromosome → tetraploidy
o Often lethal, but can have interesting
consequences
 Can lead to speciation
 Common in plants
 Happened in ancestor of teleost fishes
- Mutation rates
o How often to mutations occur? → rarely
o E. coli: 1 error in 2 × 1010 replications
o Humans: ~1 error per 108 base pairs
 → mutation rate µ = 10-8 per bp
 Per gene mutation rates scale with number of
bp
o RNA viruses (HIV, Ebola) have high mutation rates
 µ = (10-3-10-5) per bp


The inheritance of variation
- The genome:
o The genome consists of
 Protein coding genes
 Intergenic regions
o Intergenic regions
 98% of human genome
 Partly involved in gene regulation
o Protein coding genes
 Transcribed into RNA, translated into proteins
 Human: ~20,000, <2% of the genome
- The universal genetic code of life
o In genes, triplets of nucleotides (codons), code
for 20 amino acids
o Amino acids make up proteins
o Some codons code for the same amino acid
 E.g., CCT, CCC, CCA, CCG all specify
amino acid proline.
o Changes to a codon that do not change the
amino acid are called synonymous.

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, - Synonymous mutations do NOT change the protein
- Non-synonymous mutations change the protein
- Alternative splicing
o In eukaryotes, exons of the same gene can
be combined in different ways = alternative
splicing
o In humans
 Average 7 introns and 1400 bp per
exons
 Introns ~ 17 times larger than exons


Effects of mutation
- Effects of mutations on phenotypes
o Different mutations can affect very different aspects of an organism; E.g.
 Ability of a bacterium to metabolize a new substrate
 Ability of a person to learn language
o The same mutation can (sometimes) affect many traits/phenotypes
 This is called pleiotropy
o Effect of a mutation can depend on other mutations
 Epistasis
- Effect of mutation on fitness
o Many mutations have no effect on fitness (do not affect reproduction or survival) →
neutral mutations
 Especially true for intergenic mutations and synonymous mutations
o Mutations that have an effect mostly decrease fitness → deleterious mutations
o Very few mutations increase fitness (beneficial mutations)
- Germline mutations and somatic mutations
o Higher animals have separate germlines
o Germline mutations can be inherited
o Somatic mutations are not inherited but can e.g. cause cancer
o Plants, corals, sponges have no separate germline
 Somatic mutations can be inherited


Is mutation random?
- Different nucleotides and different genomic regions can have different mutation rates
- Environmental conditions can affect mutation rate (e.g., radiation)
- However, mutations are not directed
o E.g., heat stress does not cause mutations that help with heat adaptation
- In that sense, yes mutations are random


Chapter 6 of Herron and Freeman
The mixing of genetic variation in populations


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, - Allele frequency measures how common an allele is in a population
- Hardy-Weinberg equilibrium (HWE) v
- More generally, assume two alleles A1 and A2
o Their frequencies sum up to 1.
o Given allele frequency p of allele A2, the frequency of A1 is 1-p.
o With probability p a sperm or egg cell carries A2, with probability 1-p A1
o Chances of different offspring genotypes being produced:




- HWE is reached after one generation of random mating, if there is
o An infinite population size
o No natural selection
o No mutation
o No movement between populations
- No real population meets all of these conditions
o Still often close to HWE
o Deviation from HWE can be a sign of natural selection, population structure, or
assortative mating
- If the above conditions are met, no evolutionary change is expected
o Under HWE conditions, allele frequency (p) stays the same over generations
- Example: effect of selection on HWE
o β-hemoglobin locus in humans has two alleles called A and S.
 They differ by a single base in the sixth codon




o Frequencies of the genotypes at this locus among 654 adults from Musoma,
Tanganyika (Africa), and the frequencies expected if the population was at Hardy-
Weinberg equilibrium → heterozygote advantage (Malaria protection)


Recombination
- Gene mixing in genetics
o Genes on the same chromosome are linked
o Become un-linked across generations by meiotic recombination
- Linkage recombination at the population level
o New mutations appear on a haplotype with given alleles at other loci.
o Loci on the same chromosome are inherited together (if no recombination).
o As they appear, mutations are correlated with the alleles around them.
o Linkage disequilibrium measures the correlation of alleles.
 Correlation of alleles at different loci
- Linkage disequilibrium (LD) measures correlation of alleles



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