8.5 The Effects of Mutations on Gene Expression

Give examples of mutations that can have global effects on gene expression.

A nonsense mutation that generates a stop codon causes the production of a truncated, nonfunctional polypeptide. A nonsense-suppressing mutation in a tRNA gene causes the addition of an amino acid in response to the stop codon, allowing production of a full-length polypeptide.

Contrast the actions of hypermorphic, neomorphic, and antimorphic gain-of-function alleles.

Hypermorphic alleles are dominant to the wild-type alleles because the mutant proteins remain active even if the normal protein is present. Neomorphic alleles produce mutant proteins with a new function while others cause genes to produce the normal protein ectopically. Antimorphic alleles encode proteins that not only fail to provide activity of the wild-type protein, but also prevent the normal protein from functioning.

Explain why most loss-of-function alleles are recessive to wild-type, but some are incompletely dominant or (rarely) dominant.

Loss-of-function alleles completely block the protein function for null or amorphic mutations. These mutations either prevent synthesis of the protein or promote synthesis of a protein incapable of carrying out any function. When phenotype varies continuously with the amount of gene product, loss-of-function alleles are incompletely dominant. In rare dominant loss-of-function alleles, haploinsufficiency occurs when half the normal gene product is not enough for a normal phenotype, so a loss-of-function mutant allele has dominant effects.

Discuss mutations outside the coding sequence that could affect gene expression.

Mutations outside the coding sequence can impact gene expression by changing the sequence of a promoter to make it hard for RNA polymerase to transcribe. Mutations in enhancers can disrupt transcription factors from being recognized. Changes in the splice donor and splice acceptor sites can obstruct splicing as a result of absent mature mRNA and no polypeptide. Mutations affecting at the ribosome binding site would lower affinity of the mRNA for the small ribosomal subunit. Mutations will destroy the efficiency of translation and the amount of polypeptide product. Mutations in the stop codon would produce longer proteins to become unstable or nonfunctional.

Compare silent mutations, missense mutations, nonsense mutations, and frameshift mutations in terms of how they alter a gene product.

Silent mutations- change a codon into a mutant codon that specifies exactly the same amino acid. No effect on any of the phenotypes influenced by the gene. Missense mutations- change a codon into a mutant codon that specifies a different amino acid; little or no effect on protein function depending whether the substitutions are conservative or nonconservative. Nonsense mutations- change an amino acid-specifying codon to a stop codon; results in production of truncated proteins lacking all amino acids and a mutant polypeptide will be unable to function when there are missing amino acids. Frameshift mutations- results from insertion or deletion of nucleotides within the coding sequence. If that happens, unrelated amino acids or stop codons appear in the place of amino acids to cause malfunction on protein activity and destroying polypeptide function.