Page 146 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

What’s Next 305

Figure 8.34 Nonsense suppression. (a) A nonsense inefficiently to the stop codons normally found at the ends
mutation that generates a stop codon causes production of a of mRNA coding regions. If this were not the case, the
truncated, nonfunctional polypeptide. (b) A second, nonsense- suppressing tRNA would wreak havoc in the cell, produc-
suppressing mutation in a tRNA gene causes the addition of an ing a whole array of aberrant polypeptides that are longer
amino acid in response to the stop codon, allowing production of a
full-length polypeptide. than normal. One way cells guard against this possibility is
(a) A nonsense mutation to place two stop codons in a row at the ends of many
Normal gene Altered gene genes. Because a suppressing tRNA’s chance of inserting
DNA T T G Nonsense T A G an amino acid at both of these codons is very low, only a
A A C mutation A T C
Transcription Transcription small number of extended proteins arise.
mRNA 5' U U G 3' U A G
Nonsense
(stop) codon
AAC
Translation stops
tRNA Leu essential concepts
Ser Pro Ala • Point mutations in the coding sequences of a gene may
Translation modify the amino acid sequence of the polypeptide
Leu
Ala Polypeptide terminates; product.
Ser Pro Complete protein incomplete, nonfunctional • Mutations outside the coding sequences can modify gene
is formed protein is released expression by altering the amount, time, or place of
protein production.
(b) A nonsense-suppressor tRNA Nonsense (stop) codon • Loss-of-function mutations reduce or abolish gene
U A G
AUG expression. Most loss-of-function alleles are recessive to
Mutation in tRNA Tyr AUC Altered wild-type alleles. When phenotype varies continuously
anticodon
gene transcribed
into mutant tRNA Tyr with the amount of gene product, loss-of-function alleles
are incompletely dominant. In haploinsufficiency, half the
normal amount of gene product is not enough for a
Tyr Tyr Mutant normal phenotype, so a loss-of-function mutant allele has
Tyr
tRNA
Wild-type Ser Pro Ala dominant effects.
tRNA Tyr Mutant tRNA Tyr inserts tyrosine into growing • Rare gain-of-function mutations cause increased protein
polypeptide, full-length protein is produced. production, synthesis of an altered protein, or production
of the normal protein in the wrong context. Most gain-of-
Similarly, mutations in the anticodons of other tRNA genes function alleles are dominant to wild-type alleles.
can suppress UGA or UAA nonsense mutations. • Whether a mutation is recessive or dominant to wild type
Cells with a nonsense-suppressing mutation in a tRNA depends on how drastically the protein product is altered
gene can survive only if two conditions coexist with the and how sensitive phenotype is to the abnormal gene
mutation. First, the cell must have other tRNAs that recog- function.
nize the same codon as the suppressing tRNA recognized • Mutations in genes that encode molecules of the gene
before mutation altered its anticodon. Without such tRNAs, expression machinery are often lethal. Exceptions include
the cell has no way to insert the proper amino acid in re- mutations in tRNA genes that produce nonsense
sponse to that codon (in our example, the codon for tyros- suppressor tRNAs.
ine). Second, the suppressing tRNA must respond only

WHAT’S NEXT

Our knowledge of gene expression enables us to rede- stops. In addition to all of these features, eukaryotic
fine the concept of a gene. A gene is not simply the DNA genes contain introns that are spliced out of the primary
that is transcribed into the mRNA codons specifying the transcript to make the mature mRNA. Because of in-
amino acids of a particular polypeptide. Rather, a gene trons, most eukaryotic genes are much larger than pro-
is all the DNA sequences needed for expression of the karyotic genes.
gene as a polypeptide product. A gene therefore includes Even with introns, a single gene carries only a very
the promoter sequences that govern where transcription small percentage of the nucleotide pairs in the chromo-
begins and, at the opposite end, signals for the termina- somes that make up a genome. In humans, the average gene
tion of transcription. A gene also must include sequences is 16,000 nucleotide pairs in length. But the haploid human
dictating where translation of the mRNA starts and genome has roughly 3 billion (3,000,000,000) nucleotide
DNA: © Design Pics/Bilderbuch RF