The stochastic behavior of mutation (chapter 5 and a bit of chapter 7)

1. Mutations are very common. New point and short insertion/deletion mutations in an adult human is estimate at 100, 91 from the father and 9 from the mother, and 98 from non-coding and 2 from coding regions (James F. Crow, University of Wisconsin Madison). In terms of gene duplications via unequal crossing over (e.g., the hemoglobin gene family) or retrotransposition (e.g., the Alu family), it is estimated 4.4 Mbp of DNA are added to the primate genome every million years. The Alu family comprises 11% of our genome, or about 1,200,000 copies of repetitive “selfish” DNA. A new Alu “jump” occurs in one out of every 200 people (Dolan DNA Center).

2. Certain kinds of mutations are expected to accumulate in a lineage more than others: point mutations > small insertion/deletions > transpositions > gene duplications > chromosomal changes.

3. Genetic samples taken from populations that trace back to a common ancestor recently (e.g., samples taken from very closely related populations) will show an abundance of point mutations (mostly transitions) and short insertion/deletions.

4. Genetic samples taken from populations that trace back to a common ancestor with greater antiquity (e.g., samples take from distantly related species) will show variation that includes also large insertion/deletions, transpositions, and gene duplications.

5. Mutations that persist into adulthood and drift to high frequency over the generations are referred to as substitutions, at these accumulate at a clock-like rate (e.g., 1 x 10-9 substitution/site/year).

Summary. The classical view of population variation – natural selection finely hones an optimal genotype to fit a particular environment (see chapter 5) - was overly deterministic. Since the late 1960’s, genotype studies have continuously revealed considerable genetic diversity harbored within populations and species (e.g., Fig. 5.13).

Chapter 5 questions and answers:

1. Silent site mutations are unequivocally neutral.

4. See Fig. 5.6, page 153. This is a stochastic event that rarely results in a new gene with a new function – the term “rarely” is used in the context of the law of large numbers, where the rare tail of a probability distribution includes much area under the curve.

5. Most mutations are neutral to slightly deleterious, and the shared occurrences of these, especially the slightly deleterious traits, can only be explained by homology, inheritance of non-functional similarity from a common ancestor.

6. Transition point mutations, pyrimidine-pyrimidine or purine-purine, are the most common and expected to predominate the genetic variation among very closely related individuals. Genetic samples showing much transversion variation must represent individuals that trace much further back in time to an MRCA than individuals having only transition substitutions as the main extent of their genetic variation.

8. Genetic variation is the result of the stochastic processes mutation and drift. The reason natural selection works so well is that so much variation is presented to it via these processes.

11. The fate of a duplicated gene is unpredictable but limited to a few possibilities (i.e., stochastic): retain the same function, become a pseudogene, or evolve a new function (the latter of which is a rare event).

12. Consecutive sequence identity for over tens and hundreds of base pairs can only be explained by homology (see question #5). The chance of two sequences mutating from different starting sequences to arrive at the same sequence of identical consecutive nucleotides, even by selection, is (0.25)n, where n=number of consecutive nucleotides. This is a very small number for an average sequence.

13. Alleles are defined by their unique nucleotide sequence. A single transition point mutation, for example, gives rise to a new allele regardless of whether it is neutral, advantageous, or deleterious.

syllabus