Contents:
Neutral
Theory of Molecular Evolution
Negative
or Purifying selection
Positive
selection (Adaptive evolution)
Overdominance
or balancing selection
Synthetic
theory of evolution or Neo-Darwinism
Notes from Lectures “Molecular Evolution”, 2001 University College London.
Darwin
Forces of evolution?
The Beanbag
Pool = an aggregated stake to which each player has contributed.
In the simplest case, the parents contribute equally to the pool
Controversal
for large diploid populations: Gene Pool Models
Two alleles: p q, equally distributed on parent gametes: p or q
Random mating = Withdrawel from beanbag
The HW law relates the frequencies of
genes to those of genotypes in a randomly mating population with NO selection,
mutation or migration:
(p+q)2 = p2 + pq + q2
|
Genotype |
p p |
p q |
q q |
|
Frequency |
p2 |
2 pq |
q2 |
If the partents mate at random, the zygotes are in HW proportions.
With differential mortality or smaller populations, the population will no longer be in HW.
Departures from HW proportions are often
taken as evidence for selection.
With more than two alleles, the binomial expansion becomes multinomial.
Departures:
Seqall Wright;s effective population
number: Ne
Departures, caused by uneven sex ratio or unequal fertility so that alleles do not have an equal probability of coming from any parent, are adjusted in the equations by using Ne – the size of an ideal population that would produce the same random drift or consanguinity as the actual population
|
Genotype |
p p |
p q |
q q |
|
Relative Fitness |
1 |
1-s |
1-2s |
q is deleterious, and gets negatively selected for. p will reach fixation.
selective constraint: most mutations are deleterious
|
Genotype |
p p |
p q |
q q |
|
Relative Fitness |
1 |
1+s |
1+2s |
q has selective advantage, and gets positively selected for. q will spread into the population and will reach fixation.
|
Genotype |
p p |
p q |
q q |
|
Relative Fitness |
1-s1 |
1 |
1-s2 |
The heterozygote pq has a higher fitness than either pure type pp or qq. The system has a stable equilibrium at
p = s2 / (s1 + s2)
When gametes of the parent generation are drawn and united, chance alone can change allele frequency.
The probability that k alleles are p in the next generation is given by the bionomical probability:
P(k) = (2 N choose k) pk (1-p)2N-k
Genetic drift is more important in small populations then in large ones.
.
Motoo Kimura 1968, Kinag and Jukes 1969
The driving force of molecular
evolution is random fixations of neutral mutations rather than natural
selection fixing advantageous mutations.
As opposed to (1930’s): Natural selection is the driving force of evolution and random genetic drift was unimportant. Most populations are homogeneous with little variation.
The Neutral Theory does not claim that all mutations are neutral.
Strictly Neutral Theory
lethal or completely neutral mutations only.
often been rejected.
Slightly Deleterious Mutation Hypothesis
allows for mutations whose effects are slightly deleterious
changed to:
Nearly Neutral Theory
allows for both slightly deleterious and slightly advantageous mutations
involves all parameters such as population size and selective pressure and is thus almost impossible to test or refute.
The
hypothesis of molecular clock asserts that the rate
of DNA or protein sequence evolution is constant over time or among
evolutionary lineages.
e.g. hemoglobin, cytochrome c in mammals
Emile
Zuckerkandl and Linus Pauling 1965
č
reconstruction
of phylogenetic trees
č
controversial:
The rate of evolution is determined by
environmental changes and natural selection.
(believed in at that time…)
The clock is violated for most species except very closely related ones.
today: The importance of random genetic changes is generally accepted although the relative roles of mutation and selection are still being devated.