Page 140 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

8.5 The Effects of Mutations on Gene Expression and Function 299

There is nothing to prevent an mRNA from having more In eukaryotes, the small ribosome subunit binds at the 5′
than one ribosome binding site, and in fact, many prokary- cap and migrates until it encounters the initiation site.
otic messages are polycistronic: They contain the informa- • In prokaryotes, the primary transcripts are mRNAs
tion of several genes (sometimes referred to as cistrons), immediately ready for translation. In eukaryotes, primary
each of which can be translated independently starting at transcripts are processed prior to translation into mature
its own ribosome binding site (Table 8.1). mRNAs through the addition of 5′ caps and poly-A tails,
In eukaryotes, by contrast, the small ribosomal subunit as well as the removal of introns.
first binds to the methylated cap at the 5′ end of the mature
mRNA and then migrates through the 5′ UTR to the initia-
tion site. This site is almost always the first AUG codon en-
countered by the ribosomal subunit as it moves along, or 8.5 The Effects of Mutations on
scans, the mRNA in the 5′-to-3′ direction (see Fig. 8.25a and
Table 8.1). Because of this scanning mechanism, initiation in Gene Expression and Function
eukaryotes takes place at only a single site on the mRNA,
and each mRNA is monocistronic—it contains the informa- learning objectives
tion for translating only a single kind of polypeptide.
Another difference between prokaryotic and eukaryotic 1. Compare silent mutations, missense mutations,
translation is in the composition of the initiating tRNA. In nonsense mutations, and frameshift mutations in terms
prokaryotes, as already mentioned, this tRNA carries a of how they alter a gene product.
modified form of methionine known as N-formylmethionine, 2. Discuss mutations outside the coding sequence that
while in eukaryotes, it carries an unmodified methionine could affect gene expression.
(Table 8.1). Thus, immediately after translation, eukaryotic 3. Explain why most loss-of-function alleles (hypomorphic
polypeptides all have Met (instead of fMet) at their N or amorphic) are recessive to wild-type alleles, but
termini. Posttranslational cleavage in both prokaryotes and some are incompletely dominant or dominant.
eukaryotes, however, often creates mature proteins that no 4. Contrast the actions of hypermorphic, neomorphic, and
longer have N-terminal fMet or Met (see Fig. 8.26a). antimorphic gain-of-function alleles.
5. Give examples of mutations that can have global effects
Eukaryotic mRNAs Require More on gene expression.
Processing than Prokaryotic mRNAs
Table 8.1 reviews other important differences in gene We have seen that the information in DNA is the starting
structure and expression between prokaryotes and eukary- point of gene expression. The cell transcribes that informa-
otes. In particular, introns interrupt eukaryotic, but not pro- tion into mRNA and then translates the mRNA information
karyotic, genes such that the splicing of a primary transcript into protein. Mutations that alter the nucleotide pairs of DNA
is necessary for eukaryotic gene expression. Other types of can modify any of the steps or products of gene expression.
RNA processing that occur in eukaryotes but not prokary-
otes add a methylated cap and a poly-A tail, respectively, to
the 5′ and 3′ ends of the mRNAs. Mutations in a Gene’s Coding Sequence
May Alter the Gene Product
essential concepts Because of the nature of the genetic code, mutations in a
gene’s amino acid–encoding exons generate a range of re-
• In prokaryotes, transcription and translation occur percussions (Fig. 8.27a).
simultaneously. In eukaryotes, the nuclear membrane
restricts transcription to the nucleus; mRNAs are
translated only after transport into the cytoplasm. Silent mutations
• In eukaryotes, transcription initiation involves enhancer One consequence of the code’s degeneracy is that some mu-
sequences located far from the promoter. In addition, the tations, known as silent mutations, can change a codon into
chromatin of eukaryotic chromosomes must be unwound a mutant codon that specifies exactly the same amino acid.
to allow access by RNA polymerase. The majority of silent mutations change the third nucleotide
• Prokaryotic mRNAs are polycistronic such that ribosomes of a codon, the position at which most codons for the same
can translate several different polypeptides from a single amino acid differ. For example, a change from GCA to GCC
mRNA. Eukaryotes have monocistronic mRNAs that can in a codon would still yield alanine in the protein product.
be used to translate only a single protein. Because silent mutations do not alter the amino acid com-
• In prokaryotes, ribosomes bind to a sequence called the position of the encoded polypeptide, such mutations usually
Shine-Dalgarno box adjacent to the AUG initiation codon. affect neither gene expression nor phenotype.