17. Mutation, Repair, and Recombination

Most mutations are thought to be deleterious. Why, then, is it reasonable to state that mutations are essential to the evolutionary process?

Why is a random mutation more likely to be deleterious than beneficial?

Most mutations in a diploid organism are recessive. Why?

The effect of base-pair substitution mutations on protein function varies widely from no detectable effect to the complete loss of protein function (null allele). Why do the functional consequences of base-pair substitution vary so widely?

What is the difference between a silent mutation and a neutral mutation?

Describe the purpose of the Ames test. How are his⁻ bacteria used in the Ames test? What mutational event is identified using his⁻ bacteria?

In numerous population studies of spontaneous mutation, two observations are made consistently: (1) Most mutations are recessive, and (2) forward mutation is more frequent than reversion. What do you think are the likely explanations for these two observations?

Two different mutations are identified in a haploid strain of yeast. The first prevents the synthesis of adenine by a nonsense mutation of the ade-1 gene. In this mutation, a base-pair substitution changes a tryptophan codon (UGG) to a stop codon (UGA). The second affects one of several duplicate tRNA genes. This base-pair substitution mutation changes the anticodon sequence of a tRNAᵀʳᵖ from

      3′−ACC−5′ to 3′−ACU−5′

Do you consider the first mutation to be a forward mutation or a reversion? Why?

Two different mutations are identified in a haploid strain of yeast. The first prevents the synthesis of adenine by a nonsense mutation of the ade-1 gene. In this mutation, a base-pair substitution changes a tryptophan codon (UGG) to a stop codon (UGA). The second affects one of several duplicate tRNA genes. This base-pair substitution mutation changes the anticodon sequence of a tRNAᵀʳᵖ from

      3′−ACC−5′ to 3′−ACU−5′

Do you consider the second mutation to be a forward mutation or a reversion? Why?

Why are frameshift mutations likely to be more detrimental than point mutations, in which a single pyrimidine or purine has been substituted?

What is the phenotypic effect of inserting a Ds element into the maize C gene? How do Ds and Ac produce maize kernels that are mostly yellow with purple spots?

If you were to look up Gaucher disease on the OMIM website, you would see that there are three major types, designated Type I (OMIM 230800), Type II (OMIM 230900), and Type III (OMIM 231000). All three types are mutations of the gene for acid-β-glucosidase, encoded on chromosome 1. Different mutations of this gene produce the three types of Gaucher disease that differ somewhat in their symptoms and disease severity.

Thinking about the production or function of the acid-β-glucosidase enzyme, why do you suppose different mutations of this gene produce differences in symptoms and disease severity?

If you were to look up Gaucher disease on the OMIM website, you would see that there are three major types, designated Type I (OMIM 230800), Type II (OMIM 230900), and Type III (OMIM 231000). All three types are mutations of the gene for acid-β-glucosidase, encoded on chromosome 1. Different mutations of this gene produce the three types of Gaucher disease that differ somewhat in their symptoms and disease severity.

For each mutation, speculate about whether the acid-β-glucosidase enzyme is merely reduced in function or whether its production is eliminated, and explain why.