Background on neutrality and implications of models.
Evolution requires genetic variation.
Yet eventually directional evolution and genetic drift will act to decrease variation.
How much variation exists in a population for selection to work on?
Mid sixties biologists used electrophoresis to measure variability.
Technique of choice separates protein on the basis of mobility through a gel under the influence of an electric current.
Generated new estimates of "genetic diversity" of h, probability that two alleles chosen at random from all the alleles at that locus in the population are different.
or h =Sum of xi xj or 1-sum of xi xi + xjxj
Under random mating this equals the population heterozygosity and equal to the number of heterozygous individuals in classical HW populations. H for a population consisting of 25 AA, 50 Aa and 25 aa individuals is 0.5.
Electrophoresis allows a new approach where genetic diversity can also be expressed as the percent of polymorphic loci found in the population.
For example, if 20 loci are studied by electrophoresis and 16 show no variation and 4 have more than one band on the gel, then the percent polymorphism for that individual would be 4/20 X 100 = 20%. Can determine these for several individuals and obtain an average for a population or even a group.
In animals, a broad range in average heterozygosity was found and was more than expected.
Birds 15%, Insects 50%, mammals 20%, fish 30%
Scientists were astonished at the variability shown even at the protein level. These findings lead to several ideas.
Kimura was the first to propose that most of evolutionary change at the molecular level occurs as a consequence of random genetic drift, because most mutations at this level are essentially neutral. Assuming neutrality would allow populations to maintain substantial levels of variation. Also neutral alleles will not be exposed to selection in some sense and so any changes in frequency would be due to genetic drift.
Now near neutrality is proposed for many alleles.
Paper with more information for interested students, class will not be responsible for content on exams.
The first evidence proposed for neutrality or near neutrality was molecular clocks.
Molecular clocks: A concept that correlates the number of substitutions to time, assuming that (a) the mutations are selectively neutral (or nearly neutral) and (b) the substitution rate is uniform. Consequently, the number of substitutions that separate two gene copies would be a function of the elapsed time since their most recent common ancestor
The first attempt to look at molecular evolution appeared to reveal a fairly constant and characteristic rate of change per amino acid in a protein or class of proteins as expected by this theory and the term molecular clock was born. In fact today, molecular differences between species are often used to infer phylogenies because constant rates per unit time are assumed.
Kimura argues that it is easier to explain constant changes assuming neutrality than selection. Mutations occur randomly, but if most are neutral, this rate influences the number the drift to fixation and over large amounts of time that rate will appear constant. Under selection, this would require too steady of a rate for environmental change.
Evidence:rate seems constant over time
Problems: Different rates depending on groups and proteins compared. Some of this is expected as we compare groups that may represent different time periods so longer for the molecular clock to tick. Also classification schemes are somewhat arbitrary. There are many more arthropods than there are chordates and yet in the classic scheme of classification, they are both phyla. But still it looks like different organisms (For example, growth hormone and glycoprotein hormone a subunit evolve much faster in man than in rodents) even if we account for this do show different rates and certainly different proteins do (see graph below).
Problems with testing for neutrality:
The theory of neutral alleles is difficult to test because most proponents of neutrality are not discounting selection entirely, in fact they look upon selection and other forces as constraints to neutrality. Also proponents that tend to discount neutrality as a significant force even at the molecular level are not dismissing it or genetic drift, just saying eventually selection triumphs.
(There are those that proposed the extreme, that all AA replacements are the result of neutral mutation and drift, called pan-neutralists, but their interpretation is not the most common one).
Examine these two examples :
One:
Assume if you have a protein that needs a negatively charged amino acid for the resulting polypeptide to fold into the proper 3 dimensional shape to be functional. Proponents of the theory will allow selection to weed out any mutation that does not result in a negative amino acid, but will assume the any negatively charged amino acid will do, and be fixed by chance (the result of neutral mutation and genetic drift).
Also probability would predict the some irregularity to the clock in any case, so how much irregularity should be allowed?
If you find a negative amino acid that seems more or less prevalent than expected on the basis of strict neutrality, is it because of selection (maybe this is an animo acid that is more difficult to hand metabolically or more difficult to obtain in the environment). Or since we never expect perfection in data can we dismiss the deviation as due to experimental error. Again even the most forceful proponents of selection, allow for some drift.
Two:
Some argue that the clock should be influenced by generation time. Yet most protein clocks are generation independent.
A triumph for selection? Maybe not?
Species with short generation times tend to have large populations and species with long generation times tend to have small populations. So the increased rate of fixation in long generation, but small population organisms, offsets the increased number of mutations in short generation, but large population organisms, and gives rise to a "clock".
If change at the molecular level is caused to some extent by genetic drift and neutrality, then this change may restrict the variation natural selection has to work on when the organisms in question encounter novel environments. In this way, genetic drift coupled with neutrality or near-neutrality can affect the resulting adaptations at the macro level.