Question

Read just the long paragraph below and explain in your words the hypothesized evolutionary processes (note, more than one are in play) proposed to remove slightly deleterious alleles from the gene pool. Keep in mind the importance about balance between mutation rates and the consequences to individual fitness.

"At first sight, it appears paradoxical that nearly neutral mutations in essential immune genes will be efficiently removed from the species’ gene pool despite having no easily discernible impact on the immune system of individual homozygotes. One possible explanation is that these subtle variants are individually sufficient to cause a serious problem in conjunction with particular environmental stressors such as malnutrition and pathogenic microbes. Another explanation comes from decades of research into the evolution of protein molecules and the nearly neutral theory of molecular evolution (39, 45). Mathematical models predict that slightly disadvantageous nearly neutral alleles will be lost over many generations through random drift in large populations, even when these alleles reduce fecundity by as little as 1% (39). For essential immune genes, that small difference in fecundity could result from one extra bout of influenza per lifetime, which would not be perceived as clinically significant. In addition to genetic drift in large populations, truncating selection has the potential to remove nearly neutral mutations from the gene pool more rapidly (46). This model considers that, as the number of slightly damaging alleles increases in the population, by Poisson distribution a subset of individuals will inherit a larger burden of nearly neutral alleles affecting a critical function (46), for example, in RAG1, RAG2, LIG4, DCLRE1C, and PRKDC and other genes required for VDJ recombination. Although none of these mutations would be of clinical consequence individually, the chance inheritance of three or more subtle defects in the same pathway may be sufficient to cause recurrent infections or Omenn’s syndrome-like autoimmune manifestations. Previously, we demonstrated experimentally how three heterozygous loss-of-function mutations in sequential steps in a biochemical pathway—affecting Lyn kinase, its substrate CD22, and the CD22-binding tyrosine phosphatase SHP1—only precipitate B-cell deficiency in individuals that inherit all three but not any pair or single mutation (47). Some of the 23 immune genes studied here have essential roles outside the immune system, and those other functions may be more sensitive to disruption by apparently FP mutations. For example LIG4, DCLRE1C, and PRKDC are critical for DNA damage repair in all cells, and it is conceivable that small decreases in their activity could subject these variants to purifying selection over evolutionary timescales because of more rapid aging of stem cells (48)."

Answer 1

Two evolutionary processes are acting here to remove slightly deleterious alleles from the gene pool. 1) Genetic drift and 2) Truncation selection.

Genetic drift is a chance that makes a particular allele to disappear as individuals do not survive in a better way. And truncation selection is a thing which selects some individuals to breed in a perfect manner, while some individuals are not selected to breed because of a faulty allele or so.

In our example, those alleles which are mutated almost neurally, and reduce their fecundity as little as 1%, are also selected to be removed from the gene pool through genetic drift. Though this small reduction of fecundity is not clinically significant, but are lost over many generations, as they are lethal while conjugated with some other mutated genes.

Again, truncation selection is occurred as the number of nearly neutral alleles increase in the population when subset of a population inherits a larger burden of mutated alleles that affect a critical function . So, by gathering those nearly neutral mutated alleles, individuals behave less fit.

So, genetic drift and truncation selection act to reduce the nearly neutral mutations in the gene pool of a population.