11-4-05

MUTATIONS AND NEW ALLELES I


The term "mutation" refers to any permanent change in the nucleotide sequence of a DNA molecule.

Mutations that arise in somatic cells may affect the organism during its lifetime. For example, a major aspect of cancer is the accumulation of mutational changes. These mutations that occur in somatic cells are not passed on to the offspring.

Mutations that arise in cells that are precursors to the gametes become an inheritable change. Consider some random change in gene alpha somewhere along chromosome #7 to occur "right now" in you in a cell that will later go through meiosis to produce egg or sperm. If we imagine that a gamete with this change on gene alpha participates in a fertilization event that later becomes your child, we see that a new mutant allele of this gene has entered the human population.

1. What are the various ways in which mutations are classified?

Mutations get classified in a variety of somewhat overlapping ways. Table 14.1 lists the terminologies used for mutations, based on various criteria. We will use many of these terminologies as we proceed.

 

2. What are the implications of the following textbook statement (on page 626): "Spontaneous damage to DNA in human cells takes place at a rate of approximately 1 event per billion base pairs per minute."?

At first, one damaged base pair in a billion doesn't sound like much, but ....... that's about six damages occurring in every cell every minute. If left un-repaired, this rate of damage would accumulate to about 10,000 damages per day in each cell. Obviously, DNA repair must work very well. Otherwise, the continuing damage to the DNA would lead to cell death quite quickly, and we would not be here.

In general, these various repair mechanisms are very efficient, with almost all of the repair getting done in a way that returns the DNA to its original state. Once in a while, though, a mistake occurs during repair, and a mutation results.

 

3. What are the possible phenotypic effects of a single base pair change in a coding region of a gene?

Figure 14.4 shows what can result from a DNA base pair change in one particular codon sequence. A random base pair change in the DNA will change the codon in the mRNA into one of nine possibilities. Consider, for example, the UAU codon (one of two codons for the amino acid tyrosine). Six of the 9 possible changes give "missense mutations" (a different amino acid inserted at that spot in the protein), one of the possibilities (UAU to UAC) gives a "silent mutation" (the same amino acid is inserted at that spot in the protein), and two of the possibilities give "nonsense mutations" (the codon has been changed into a stop codon).

 

4. What are the effects of base pair additions or deletions?

Figure 14.5 shows this.

 

5. What is an example of a long-ago mutation that became a new allele that is now present in a significant fraction of the human population?

Figure 14.3 shows the mutation that is the genetic basis of the inherited disease sickle-cell anemia. Essentially everyone who has this disease is homozygous for the g allele shown in part b of the figure, which arose from an AT to TA transversion mutational change in the sixth codon of the B-globin gene, changing the codon from one for glutamic acid to one for valine. The g allele has become quite common in the human population because being heterozygotic (Gg) results in enhanced resistance to malaria.