Gene Expression: The Flow of Information from DNA to RNA to Protein III

In E. coli and other proks, transcription takes place in an _____ ________ space undivided by a nuclear membrane. Translation occurs in the same open space and is sometimes coupled directly with _______

This coupling is possible because transcription extends mRNAs in the same ________ direction as the ribosome moves along the mRNA. (Result?)

Differences in prokaryotes and eukaryotes (5-overview)-4(transcription)-3(translation) (*specific)

Because of this scanning mechanism, initiation in euks takes place at only a single site on the mRNA, and each mRNA is _________ (meaning) it contains the info for translating only _____ kind of _______

Immediately after translation, euk polypeptides all have _____ instead of ______ at their N termini. Posttranslational cleavage events in both proks and euks often create mature proteins that no longer have N-termini _____ or _____

One consequence of the code's degeneracy is that some mutations, known as ______ mutations, can change a codon into a mutant codon that specifies exactly the same amino acid

The majority of silent mutations change the ______ nucleotide of a codon, the position at which most codons for the same amino acid ______

Why do silent mutations usually have no effect on any of the phenotypes influenced by the gene

Missense mutations

If the substituted amino acid has chemical properties similar to the one it replaces, then it may have _____ or ____ effect on protein function. Such subs are ________

By contrast, ___________ missense mutations that cause substitution of an amino acid with very different properties are likely to have more noticeable consequences

Why is the effect on phenotype of any missense mutation difficult to predict?

Nonsense mutation

Nonsense mutations result in the production of ________ proteins lacking all amino acids between the amino acid encoded by the mutant codon and the C terminus of the normal polypeptide. The mutant polypeptide will be _______ to function if it requires the missing amino acids for its activity.

Frameshift mutations result from the ________ or ________ of nucleotides within the coding sequence

If the number of extra or missing nucleotides is not divisible by ____, the insertion or deletion will skew the _______ ______ downstream of the mutation.

As a result, frameshift mutations cause unrelated _____ ______ or premature _____ _______ to appear in place of amino acids critical to protein activity, destroying or diminishing polypeptide function

Name all of the mutations depicted 

Mutations that produce a variant phenotype are not restricted to alterations in _______

Gene expression depends on several signals other than the actual coding sequence (result)

Changes in the sequence of a promoter that make it hard or impossible for RNA polymerase to associate with the promoter diminish or prevent _________.

Likewise, mutations in enhancers that disrupt them from being recognized by ________ ______ also diminish the transcription of euk genes

Mutations in a termination signals can diminish the amount of ______ produced and thus the amount of ______ product

Three sites in euks that allow splicing to join exons together with precision in the mature mRNA

Changes in any of those three sites can obstruct _________. In some cases, the result will be the absence of ______ ______ and thus no _________. In other cases, the splicing errors can yield aberrantly _______ mRNAs that encode _______ forms of the protein

Mature mRNAs have ribosome binding sites and in-frame stop codons indicating where translation should _____ and ____

Mutation affect phenotype in 2 ways. Name them

What do we call any mutation inside or outside a coding region that reduces or abolishes protein activity in one of the many ways prev. described

Loss of function alleles that completely block the function of a protein are called _____ or ________ mutations. (What are the two possible results)

Explain why null or amorphic alleles are usually recessive to wild-type alleles using the figure (3-story)

hypomorphic mutation

Hypomorphic alleles are usually _______ to wild-type alleles for the same reason that amorphic alleles are usually ________

Some combinations of alleles generate phenotypes that vary continuously with the amount of functional gene product, giving rise to Incomplete dominance. Explain with the example presented in the figure (4-story)

With phenotypes that are exquisitely sensitive to the amount of functional protein produced, even a relatively small change of ______ or less can cause a switch between distinct phenotypes. Therefore, a heterozygote for a loss of function mutation that generates less than the normal amount of functional gene product may look ________ from the wild-type organism

Haploinsufficient

The number of haploinsuff. genes in humans is ~ _____. Detail an example

Why are the large majority of mutations in most genes loss of function alleles?

However, rare mutations that either enhance a protein's function, confer a new activity on a protein, or express a protein at the wrong time or place act as _________ __________ ________

Why are gain of function alleles almost always dominant to wild-type alleles?

Many dominant mutant alleles are _____ when homozygous

Hypermorphic mutations (define)
How do you know if it is dominant?

A hypermorphic mutation in the human FGFR3 gene results in ________, the most common form of dwarfism (how)

Achondroplasia/FGF 4-story:

Neomorphic mutation

Ectopic expression

Some neomorphic alleles produce mutant proteins with a ____ function, while others cause genes to produce the normal protein but at an inappropriate _____ or _____ (______ _______)

Neomorphic allele that expresses a normal protein ectopically is the Antp^Ns mutant allele of the Drosophila gene Antennapedia

Why is Antp^Ns dominant?

Dominant negative alleles

Explain dominant negative (aka antimorphic genes) by considering a gene encoding polypeptide that associates with three other identical polypeptides in a four subunit enzyme (4-Story) 

If more than one gene encoded the same molecule with a role in gene expression, a mutation in one of these genes would not necessarily be _____ and might even be ______. Bacterial geneticists have found, that mutations in certain tRNA genes can suppress the effect of a _______ mutation in other genes. The tRNA-gene mutations that have this effect give rise to _______ ________ _______.

Explain nonsense suppressor t-RNAs by considering the otherwise wild-type E. coli population with an in-frame UAG nonsense mutation in the tryptophan synthetase gene (4-story)