Genen en Evolutie
Evolutionary change is a change in allele frequencies.
Factors affecting genetic variation in a population
1.
2.
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7.
X-linked genes
Linkage disequilibrium
Gametic Phase Disequilibrium
Darwinian selection
Meiotic Drive
Genetic Drift
Population Structure
Random Mating (rm, inbreeding) - non-overlapping generations
Population STructure ( size, subdivision)
Migration (gene flow)
Genetic System (haploid/ diploid, (a)sexual)
Sex differences in allel frequencies
Complex selection models
 Fluctuating fitness
 Differential selection in the sexes
 X-linked genes
 Frequency dependent selection
 Density-dependent selection
 Fecundity selection
 Age-structures populations
 Heterogeneous environments and clines
 Diversifying selection
 Gametic selection
 Meiotic Drive
 Epistasis
 Evolution of recombination rate
 Sexual selection
 Kin selection
Sex-linked genes
Y-chromosome is basically 'empty' - males are homozygote as there is no allel on
the Y chromosome.
Linkage disequilibrium
Linkage disequilibrium (D = 1) exists when gene A is always associated with
gene B and gene a is never associated with gene B. Linkage equilibrium (D = 0)
exists when gene A is associated to B just as much as to b. If recombination (r) =
0, then there is a strong disequilibrium, if r = 0.5 (maximum, otherwise the genes
could also be on another chromosome) then the disequilibrium decays very
quickly to an equilibrium.
The tendency for alleles of genes close together in the same chromosome to
remain together in inheritance: a non-random association between alleles of
different genes (against Mendel's second law of independent assortment).
A marker is linked to a QTL if the phenotype distributions shift when the
genotype at the marker locus changes.
They can undergo recombination. The frequency of AB gametes is used to trace
the decay of linkage disequilibrium. Recombination reduces linkage
disequilibrium.
Gametic Phase Disequilibrium
Alleles associated for other reasons than physical linkage.
Population admixture = the mixing of genomes of divergent parental taxa.
Chromosomal inversions = suppress recombination in inversion
heterozygotes
Genetic coadaptation = alleles function optimally in own genomic
background; recombination produces unfit genotypes; purifying selection
selectively removes recombinants
Runaway sexual selection
Inbreeding
Darwinian Selection
Evolution:
Trait variation
Heritability
Different reproductive successes among individuals correlated with
variation in trait
Genotypic + Environmental variation = phenotypic variation = fitness variation
There is different selection is different life stages.
Basic model:
Zygote stage ->
Adult stage
viability selection
->
Zygote stage of offspring
mating & inheritance
Models of selection
1. Directional selection
2. Disruptive selection
3. Stabilizing selection
Level of dominance influences the spread of beneficial mutants.
Dominant alleles: rapid initial spread, slow to fixation
Recessive alleles: slow initial spread, rapid fixation
1. Partial dominance wAA ≥ wAa ≥ waa => A will fixate
2. Complete dominance; partial dominance with h=1.
3. Overdominance wAa > waa, wAA
Heterozygote advantage: convergence to stable interior equilibrium (rare,
Sickle cell anemia and Maleria relationship) w_ at local maximum
4. Underdominance wAa < waa, wAA
Heterozygote disadvantage: unstable equilibrium w_ minimal at
minimum, two optimal w_: p converges to 0 or 1.
Fitness
Marginal fitness is of a genotype. Mean fitness is of a population. Average w
against allele frequency is a fitness landscape. Highest peak is highest fitness; but
there are local peaks as well. Valley's can be crossed due to drift (Wright's
shifting balance theory).
Mutation
Introduces novel allelic variants (source of all genetic variation), thus acting as
an evolutionary force (albeit a very slow one). However, most mutations have
little effect on survival and reproduction. The effective selective effects depend
on the effective population size. Big populations (typically 'old' phylogenetic
organisms like prokaryotes) have low gene complexity (fixation of an allele takes
longer) and therefore deleterious near-neutral mutations are easily removed.
Smaller population (typically 'new' phylogenetic organisms like vertebrates)
have high gene complexity (allele fixation is quicker) and therefore deleterious
near-neutral mutations behave neutral and stochasticly accumulate. (So higher
genome complexity and lower population size enhances accumulation of
deleterious alleles).
Most mutations get lost rapidly; fixation takes a long time and depends on the
population size.
Steady influx of deleterious alleles; counteracted by purifying selection. There is
balance if the change by mutation is exactly counteracted by in mutation; change
is 0. The mutation rate can be derived from a line in a graph: slope is µ.
The infinite-alleles model assumes each mutation yields an unique allele, and
therefore all physically indistinguishable alleles are Identical By Descent
(autozygous).
The 'age' of alleles and whether there is selection can be derived from the
frequency and linkage disequilibrium range. Y
Frequency
LD range
No selection (neutral)
Young
low
long
Old
high
short
Selection
Young
high
long
Meiotic drive
This causes non-Mendelian segregation in heterozygous individuals: an allele has
a higher frequency in the gametes.
Driving effect = k = proportion of driving alleles in gametes from a heterozygous
individual
Genetic Drift
Is acting in a finite population; which is always. Infinite gamete pool: the ones
forming a new organism are only a sample. So by chance a certain allele can get
favoured and therefore fixed (heterozygosity = 0). Fluctuations in allele
frequency are given by the binomial distribution. Allele frequencies in individual
populations fluctuate, but the average allele frequency stays constant.
Chance of fixation depends on the initial allele frequency (high frequency, short
time to fixation; low frequency, long time to fixation - persistence time longest
with p = 0.5) and population size (small N is more 'severe' drift, large N is less
'severe' drift).
It is an evolutionary mechanism, but not systematic.
In the initial population all alleles are unique and therefore NOT Identical By
Descent (IBD). If an alleles fixates than they all will be IBD. The probability that
alleles are IBD is the Fixation Index F. Every generation F increases by a factor
1/2N. Increase in autozygosity (is fixation) is dependent on N, and converges to
1.
Population structure
Inbreeding
Mating between close relatives; increase in autozygosity. Only dominant alleles
are expressed unless you're homozygous for a recessive. Many recessive alleles
are deleterious, which often results in a lower fitness. Due to inbreeding the
genetic load of a population increases (eg dwarfism chondrodystrophy, less
capable to handle harsh weather conditions, susceptible to disease) which is
called an inbreeding depression.
To reduce an inbreeding depression there is heterosis / hybrid vigor and genetic
rescue.
Population divergence
Sub-populations diverge randomly in allele frequencies (genetic drift);
heterozygosity decreases in sub-populations relative to the total population.
1) Continent Island Model - One way migration from infinitely large mainland
population to finite size island population
2) Infinite Island Model - Same rate of migration between all populations
(identical by size) - Migration-drift equilibrium. Als mNe (number of
immigrants/generation) is lower than 1.0 the population is genetically isolated.
3) Stepping Stone Model - Each subpopopulation of size N exchanges individuals
with each adjacent subpopulation (migration only between 2 populations).
HI = gemiddelde waargenomen heterozygotie in een subpopulatie
HS = gemiddelde verwachte heterozygotie in een subpopulatie
HT = gemiddelde verwachte heterozygotie in de totale populatie, berekend uit de
gemiddelde allelfrequenties van alle subpopulaties in de populatie
FIS = afname gemiddelde verwachte heterozygotie door non-random mating
(inteelt)
FST = afname gemiddelde verwachte heterozygotie door populatiestructuur
(genetic drift in kleine populaties)
FIT = afname gemiddelde verwachte heterozygotie door nonrandom-mating én
populatiestructuur
Genen en Evolutie
Mutations - molecular genetic variation
SNPs - Single Nucleotide Polymorphisms
VNTRs - Variable Number of Tandem Repeats
Gene duplication / Copy number variation
Indels - Insertions / Deletions
Chromosome rearrangement - inversion, Translocation, Fusion
Heredity
Nucleotides are complementary, can form diesterbonds to create
macromolecules and can be replicated. They code for proteins. Also ribozymes
exist (self-splicing introns, ribonuclease P, ribosomal RNA, virus genomes): selfcatalyzation. Therefore the first 'living' molecule was presumable RNA because
the 2' hydroxyl group allows more 3D structure, plays catalytic roles, the DNA
precursors are made of RNA and ribose is easier to be synthesized than
deoxyribose.
Gene duplication
Genes can duplicate. If there is selective pressure on both genes, both stay
similar. If there is selective pressure on just one gene one copy degrades or
acquires a new function. Example: fem and csd are sex determining loci;
evolution is restricted. Ways of duplication:
 Unequal crossing over
 Unequal sister chromatid exchange
 During DNA replication
Duplication lead to homologous genes
Evolutionary consequences of concerted evolution are the selective advantage of
a new mutation may be greatly amplified if it is passed to all members of the
family and it may prevent redundant copies to become non-functional. Gene
conversion is a mechanism for concerted evolution.
Duplications can lead to gene (super)families with different (but
sometimes similar) functions. eg. Hox and Globin genes.
Three classes of multigene families
1) Simple sequences; no known gene product, often many copies. Fingerprint loci
eg.
2) multiplicational families; functional gene product with strong similarity
between members. eg Ribosomal RNA genes.
3) informational families; homologous but considerable differences in sequence,
overlapping but functional differences. eg. Hemoglobin and antibody genes.
Whole genome duplication is also possible. Creates polyploids.
Exon-intron structure
Exons code, intron are non-coding. Introns are important as they might regulate
gene expression (a long intron causes slow transcription) and they allow
alternative splicing to yield more than one mRNA from the same gene. Introns
often mark the border of functional units of proteins and position conserved
during evolution. Makes domain shuffling possible.
Transposable elements
Are pieces of DNA with special features that can move around in the genome.
They are conservative and replicative; they increase in copy number via RNA
(long terminal repeats - retrotransposon) and via DNA (terminal inverted
repeats). They can jump into coding parts (disrupt function), regulatory regions
(disrupt or enhance function) and structural domains (alter state/chromatin).
They are also involved in Unequal Crossing Over and Sister Chromatid Exchange
by introducing similar, repeated sequences all over the genome. They can also be
involved in deletion of genome parts by recombination between transposon
sequences.
Point mutation
Base-pair substitutions in DNA sequences because of a polymerase error or
during repair of damaged DNA; creates new alleles.
Chromosome inversion
Is the flipping and reannealing of a chromosome segment. A double strand
breaks by ionizing radiation and as a result there is tighter linkage and
heterozygotes cannot recombine normally.
Polyploidization
Is the addition of a complete set of chromosomes (Whole Genome Duplication)
cuased by errors during meiosis and/or mitosis. It results in possibly a new
species.
Genome Expression Patterns
Although 98.5% of our coding DNA is identical to that of a Chimpanzee, we only
have 29% identical proteins. This has to do with gene expression. Mutations in
regulatory regions of genes can cause considerable effects at the level of gene
expression.
The link between evolution at DNA level and phenotypic diversity involves
the cis-regulatory elements acting as units of evolutionary change.
Regulatory evolution...
 enables pleiotropy
 enables developmental modularity
 rich and continuous source of variation
 creates novelty
 Can be from pre-existing elements or de novo evolution
Even though the DNA sequence may look completely different; the 3D structure
of the protein it is coding for might be very similar.
There are different genotypes coding for the same phenotype; they can give rise
to different new phenotypes upon mutation.
Genen en Evolutie
Theories
Mendel's laws
Biometrics
Mendelians
Modern Synthesis
Genetic ánd environmental factors result in a continuous distribution of fenotypes and
genotypes.
Classical theory (selectionist)
Balancing theory (selectionist)
Neutral theory
Many mutations have little effect on survival or reproduction, and their fate is determined largely
by genetic drift. A balance between recurrent mutation and genetic drift maintains most genetic
polymorphisms.
Infinite-alleles model
Assumes each new mutation yields an allele that is unique for the population. Alleles that are
physically indistinguishable are assumed to be Identical By Descent. All homozygous genotypes
are therefore also assumed to be autozygous.
Fisher-Muller model
Hill-Robertson effect
Hardy-Weinberg principle
The distribution of allele frequencies in an infinite population under certain assumptions is
summarized in a formula. Null model.
Muller's ratchet
Wright-Fisher model
In a finite population size N, the alleles transmitted from parent to offspring correspond to a
random sample (2N) - genetic drift. Fluctuations in allele frequency are given by the binomial
distribution. There is always fixation.
Wright's F-statistic
Probability that alleles are Identical By Descent is F.
Wright's shifting balance theory
Sometimes a population gets stuck on local maximum in fitness landscape (globally suboptimal) > they can 'cross valleys' by genetic drift.
Morgan's White Mutant
Discovery of a white eyes Drosophila male enables Morgan to demonstrate that genes are carried
on chromosomes, and are the mechanic basis of heredity and explained the phenomenon of
genetic linkage.
Wahlund effect
Jukas-Cantor model of DNA evolution
4 nucleotides; each has a 0,25 chance of changing into another nucleotide
Genen en Evolutie
Toepassingen
Evolution of Sex
Sex = recombination of genetic material
negative effects:
1) waters down your genome
2) breaks down coadapted gene complexes
positive effects:
1) Fisher-Muller model: recombination speeds up adaptive evolution as
lineage with favorable mutation displaces another lineage ("clonal
interference"). Only in large populations.
2) Hill-Robertson effect: sexual equivalent of clonal interference. New
favorable mutations probably occur in different backgrounds. With increase
frequency => negative linkage disequilibrium: until linkage disequilibrium
decays, interference slows down adaptive evolution.
3) Muller's ratchet: most mutation are deleterious. In asexuals there is
occasional loss of fittest genotype; this is irreversible and asexual lineages
accumulate deleterious mutations. When the mutational load becomes too large
then extinction occurs ("mutational meltdown"). Recombination/sex restores
mutation free genotype.
Evolution of sex chromosomes
There are different ways of sex determination in animals (Male or Female
heterogamety, Haplodiploidy, environmental sex determination). Mammals = y
chromosomes degenerated: has SRY gene that determines male sex.
Sex chromosomes have evolved multiple times: Pairs of ancestral autosomes
have evolved into sex chromosomes. Sex chromosomes or different species show
homology to autosomes in the other species but not to sex chromosomes.
Origin
1. Autosomal chromosomes
2. Sex Determining (SD) gene acquisition (eg SRY)
3. Sexually Antagonistic (SA) genes linkage
a. gene that increases fitness of only one sex, and decreases fitness of
the other
4. Suppression of recombination
a. If sexual antagonistic genes get on the other sexual chromosome,
the fitness is decreased and therefore this will not happen:
recombination get suppressed because it isn't beneficial. (eg. the
SA genes on males will not recombine on the X chromosome
because it reduces female fitness).
5. Degeneration - deleterious genes are accumulated
a. Muller's ratchet (no mutation - X mutation free, Y keeps
deleterious)
b. Genetic hitchhiking (strong mutation - X uncoupled beneficial and
deleterious, Y - hitchhiking of deleterious gene with beneficial
gene)
c. Ruby in the rubbish (weak mutation - X uncoupled beneficial and
deleterious gene, Y - purifying selection loses deleterious and
beneficial mutation)
6. Transposition of SD gene to new autosomal pair and loss of degenerated Y
Neo-sex
1. XA or YA fusion
2. Y or X fission
3. reciprocal translocation or Robertsonian fusion
Molecular markers
1. Restriction Fragment Length Polymorphism (RFLP)
2. DNA fingerprinting
3. Amplified Restriction Fragment Length Polymorphism (AFLP)
4. Microsatellites
Mutate by one repeat unit at the time, with a tendancy to grow and
increase in mutation rate
Insertions more frequent than deletions
Long alleles mutate more frequently than short alleles
Thus, infinite alleles model (basis for Fst) is no longer valid.
5. Single Nucleotide Polymorphisms (SNPs)
Phylogeny
Tree must reflect Identity by Descent which is based on homology. Homology in
DNA sequences (positional) is achieved with alignment software.
Homoplasmy
- parallel evolution
- convergent evolution
-secondary loss
Monophyletic clade: pattern of shared ancestry; all organisms in group share
same ancestor
Paraphyletic clade: share same ancestor, but not all organisms are included
(rather incorrectly excluded - but easily detected by molecular phylogenetics).
Polyphyletic: different ancestors: occur when there has been a lot of
morphological and functional convergence
Trees have to show 1) order and 2) amount of change and 3) time-depth
Cladogram (length doesn't mean anything)
Phylogram (length has meaning)
Unrooted tree
Parsimony: shortest tree is the best tree; a rule not an evolutionary theory
Maximum Likelihood
Bayesian methods
4 nucleotides; each 0.25 chance?
Transitions (A to G (purines) and C to T (pyrimidines)) are easier than
transversions (A tot C or T, etc).
Most changes occur if nucleotide in third position changes in protein code.