Genetik

“It is altogether unlikely that two genes would have identical selective values under all the conditions under which they may coexist in a population. … cases of neutral polymorphism do not exist … it appears probable that random fixation is of negligible evolutionary importance”
-Ernst Mayr
Neo-Darwinism
1930’s:
⎯ no way to test the predictions of different schools
⎯ arguments centered on mathematical models
1950’s and 1960’s:
⎯ protein sequencing (slow and painful)
⎯ protein gel electrophoresis (fast and cheap

Protein electrophoresis: big changes in the 1960’s
A) Diagram of a protein gel electrophoresis apparatus, and (B) a photograph of a “stained” protein gel, the blue “blotches” are the proteins, their position indicates how far they migrated in the electric field.

Lewontin and Hubby (1966) suggested that some of the polymorphism must be neutral

Genetic load
Genetic load: the extent to which the fitness of an individual is below the optimum for the population as a whole due to the deleterious alleles that the individual carries in its genome.

Genetic load: the difference between the average fitness of the population and the fitness of the best genotype. It measures the probability of selective death of an individual in a population.
W = average fitness
Genetic load (L) = 1 - W

Genetic load an Example…
Selective death (or genetic death): the chance that an individual will die without reproducing as a consequence of natural selection. [e.g.,15% of offspring in above]

There is a cost to selection, in genetic death, during this time period

Genetic load : Sources
1. Mutational load
Substitutional load [Haldane’s load]
3. Segregational load

Genetic load : Mutation

Mutational load is minor:
Equilibrium yields a polymorphism involving an allele that is very rare in the population
The load is trivial for the population, as the required excess reproductive capacity is not large

Defining Directional Section
Directional selection: selection that favours the phenotype at an extreme of the range of phenotypes
Directional selection: can be subdivided into two broad categories. These subtypes have been given different names, leading to a possible point of confusion. The next page is an attempt to clarify this issue

Defining two types directional selection
Type 1:
Positive Darwinian selection: directional selection for fixation of a new and beneficial mutation in a population.

Positive selection: Same as above. [Note that the above term is also shortened to “Darwinian selection”; this is a bad habit of which I am very guilty.

Type 2:
Negative Darwinian selection: directional selection for removal of a new and deleterious mutation from a population.
Negative selection: same as “negative Darwinian selection”.
Purifying election: same as negative selection.

Genetic load: segregational
Segregational load is a big problem for the balance school:
Well known examples exist; Haemoglobin, MHC locus, etc.
Balance school would extend this to most polymorphic loci in the genome. Let’s see if this will work

Humans:
30% of loci are polymorphic (from Harris 1966)
30,000 genes (from recent genome projects), so 9000 are polymorphic
Let’s assume a very small load on average: L = 0.001
Let’s assume that only half are under balancing selection (4500) [remember the balance school predicted a majority would be under balancing selection]
Fitness of an individual locus = 0.999
Fitness over whole genome = 0.9994500 = 0.011
Load = 1- 0.011 = 0.989 [That is huge!!!]
Cost = 0.989/0.011 = 89 [Do you know of any humans with families that big?

Genetic Load: Other
1. Recombinational Load
2. Incompatibility Load
3. Lag Load
Note: all load arguments tend to be based on overly-simplistic models.

Neutral Theory of Molecular Evolution
Motoo Kimura:
troubled by cost Haldane’s dilemma:
1 substitution every 300 generations
troubled by Zukerkandl and Pauling’s (1965) molecular clock:
1 substitution every 2 years
Published a model of neutral evolution in 1968
Jack King and Thomas Jukes:
Independently arrived at same conclusion as Kimura
Published (1969) under the provocative title “Non-Darwinian evolution”
I cannot over emphasize how radical this idea was at that time.