Background on neutrality and implications of models.
Evolution requires genetic variation.
Yet eventually directional selection and genetic drift will act to decrease variation. This is a natural consequence of these processes and biologists were at one time concerned that most evolution, or change in the direction of adaptation, would cease.
Researchers became very interested in how much variation existed in natural populations 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
Under random mating this equals the population heterozygosity and equal to the number of heterozygous individuals in classical HW populations. Genetic diversity for a population consisting of 25 AA, 50 Aa and 25 aa individuals would be 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 at the protein level and even in proteins playing important roles in growth and maintenance. But is this variation enough? These findings and considerations of how variability could be maintained, even during strong selection, lead to several ideas, the most important of these is the role of genetic drift in the process.
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. Genotypes are composed of a large number of alleles that may be only slightly deleterious or advantageous. These would essentially not be seen by selection on the entire phenotype and found in phenotypes of even high fitness. These alleles then would simply be maintained in the population by drift until they in new environments could become much more deleterious or advantageous.
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Paper with more information for interested students, class will not be responsible for content on exams.
Read the following. You should become familiar with the concept of a molecular clock since it is the basis for most phylogenies that use protein or nucleic acid data.
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
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 in some groups versus others. 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 even if we account for this, do show different rates and certainly some proteins do. But how variable given these considerations should different rates among protein amino acid substitutions be to reject neutrality?
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. So they would acknowledge that some proteins because of vital roles they play, may be more strongly selected than others. They simply hold most amino acid substitution is neutral.
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. But neutrality could still explain much of the variation we see at the molecular level.
(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 amino 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. The shorter the generation time, the greater the number of mutation, including neutral ones, so species with short generations times should evolve faster. 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 similar "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.
So now, most biologists accept that genetic drift may drive the changes in biology over time we see in organisms. Some hold that drift may be as important as selection. The argument continues and, the relative influences of natural selection versus genetic drift in shaping change, is one of the major questions current evolutionary studies hope to solve.
Neutrality remains the number one theory for explaining the prevalence of variation at the genic level.