Mutations are changes in the genetic material of a cell or virus Concept 17.5: Point mutations can affect protein structure and function Mutations are changes in the genetic material of a cell or virus Point mutations are chemical changes in just one base pair of a gene The change of a single nucleotide in a DNA template strand can lead to the production of an abnormal protein Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Wild-type hemoglobin DNA Mutant hemoglobin DNA 3 C T T 5 3 C A T 5 Fig. 17-22 Wild-type hemoglobin DNA Mutant hemoglobin DNA 3 C T T 5 3 C A T 5 5 G A A 3 5 G T A 3 mRNA mRNA 5 G A A 3 5 G U A 3 Figure 17.22 The molecular basis of sickle-cell disease: a point mutation Normal hemoglobin Sickle-cell hemoglobin Glu Val

Types of Point Mutations Point mutations within a gene can be divided into two general categories Base-pair substitutions Base-pair insertions or deletions Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Figure 17.23 Types of point mutations Wild-type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Amino end Carboxyl end A instead of G Extra A 3 5 3 5 5 3 5 3 U instead of C Extra U 5 3 5 3 Stop Stop Silent (no effect on amino acid sequence) Frameshift causing immediate nonsense (1 base-pair insertion) T instead of C missing 3 5 3 5 5 3 5 3 A instead of G missing 5 3 5 3 Stop Figure 17.23 Types of point mutations Missense Frameshift causing extensive missense (1 base-pair deletion) A instead of T missing 3 5 3 5 5 3 5 3 U instead of A missing 5 3 5 3 Stop Stop Nonsense No frameshift, but one amino acid missing (3 base-pair deletion) (a) Base-pair substitution (b) Base-pair insertion or deletion

Silent (no effect on amino acid sequence) Fig. 17-23a Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Amino end Carboxyl end A instead of G 3 5 5 3 Figure 17.23 Types of point mutations U instead of C 5 3 Stop Silent (no effect on amino acid sequence)

Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Fig. 17-23b Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Amino end Carboxyl end T instead of C 3 5 5 3 Figure 17.23 Types of point mutations A instead of G 5 3 Stop Missense

Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Fig. 17-23c Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Amino end Carboxyl end A instead of T 3 5 5 3 Figure 17.23 Types of point mutations U instead of A 5 3 Stop Nonsense

Frameshift causing immediate nonsense (1 base-pair insertion) Fig. 17-23d Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Amino end Carboxyl end Extra A 3 5 5 3 Figure 17.23 Types of point mutations Extra U 5 3 Stop Frameshift causing immediate nonsense (1 base-pair insertion)

Frameshift causing extensive missense (1 base-pair deletion) Fig. 17-23e Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Amino end Carboxyl end missing 3 5 5 3 Figure 17.23 Types of point mutations missing 5 3 Frameshift causing extensive missense (1 base-pair deletion)

Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Fig. 17-23f Wild type DNA template strand 3 5 5 3 mRNA 5 3 Protein Stop Amino end Carboxyl end missing 3 5 5 3 Figure 17.23 Types of point mutations missing 5 3 Stop No frameshift, but one amino acid missing (3 base-pair deletion)

Substitutions A base-pair substitution replaces one nucleotide and its partner with another pair of nucleotides Silent mutations have no effect on the amino acid produced by a codon because of redundancy in the genetic code Missense mutations still code for an amino acid, but not necessarily the right amino acid Nonsense mutations change an amino acid codon into a stop codon, nearly always leading to a nonfunctional protein Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Insertions and Deletions Insertions and deletions are additions or losses of nucleotide pairs in a gene These mutations have a disastrous effect on the resulting protein more often than substitutions do Insertion or deletion of nucleotides may alter the reading frame, producing a frameshift mutation Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Mutagens are physical or chemical agents that can cause mutations Spontaneous mutations can occur during DNA replication, recombination, or repair Mutagens are physical or chemical agents that can cause mutations Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Concept 17.6: While gene expression differs among the domains of life, the concept of a gene is universal Archaea are prokaryotes, but share many features of gene expression with eukaryotes Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Comparing Gene Expression in Bacteria, Archaea, and Eukarya Bacteria and eukarya differ in their RNA polymerases, termination of transcription and ribosomes; archaea tend to resemble eukarya in these respects Bacteria can simultaneously transcribe and translate the same gene In eukarya, transcription and translation are separated by the nuclear envelope In archaea, transcription and translation are likely coupled Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

RNA polymerase DNA mRNA Polyribosome Direction of 0.25 µm Fig. 17-24 RNA polymerase DNA mRNA Polyribosome Direction of transcription 0.25 µm RNA polymerase DNA Figure 17.24 Coupled transcription and translation in bacteria Polyribosome Polypeptide (amino end) Ribosome mRNA (5 end)

What Is a Gene? Revisiting the Question The idea of the gene itself is a unifying concept of life We have considered a gene as: A discrete unit of inheritance A region of specific nucleotide sequence in a chromosome A DNA sequence that codes for a specific polypeptide chain Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Fig. 17-25 DNA TRANSCRIPTION 3 Poly-A RNA polymerase 5 RNA transcript RNA PROCESSING Exon RNA transcript (pre-mRNA) Intron Aminoacyl-tRNA synthetase Poly-A NUCLEUS Amino acid AMINO ACID ACTIVATION CYTOPLASM tRNA mRNA Growing polypeptide Cap 3 A Activated amino acid Poly-A P Ribosomal subunits Figure 17.25 A summary of transcription and translation in a eukaryotic cell E Cap 5 TRANSLATION E A Anticodon Codon Ribosome

In summary, a gene can be defined as a region of DNA that can be expressed to produce a final functional product, either a polypeptide or an RNA molecule Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings