Human Horse Accumulation of additional mutations Human Horse Divergence into different species to create orthologs Accumulation of different mutations Gene duplication to create paralogs Ancestral globin gene
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Take a look at the α-globin and β-globin amino acid sequences. Which sequences are more similar, the α globin in humans and the α globin in horses, or the α globin in humans and the β globin in humans? Based on your answer, would you conclude that the gene duplication that gave rise to the α-globin and β-globin genes occurred before or after the divergence of humans and horses? Explain your reasoning.
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- To construct an “interactome” like the one shown inFigure 9-21, scientists identify all of the protein interactions in a particular tissue or cell type. Comparison ofinteractomes from human muscle versus human braintissue reveals very different patterns. If you were the scientist involved in this study, how would you explainthese results?The amino acid sequence of part of a protein has beendetermined:N . . . Gly Ala Pro Arg Lys . . . CA mutation has been induced in the gene encodingthis protein using the mutagen proflavin. The resultingutant protein can be purified and its amino acidsequence determined. The amino acid sequence of themutant protein is exactly the same as the amino acidsequence of the wild-type protein from the N terminus of the protein to the glycine in the preceding sequence. Starting with this glycine, the sequence ofamino acids is changed to the following:N . . . Gly His Gln Gly Lys . . . CUsing the amino acid sequences, one can determinethe sequence of 14 nucleotides from the wild-typegene encoding this protein. What is this sequence?When 1 million cells of a culture of haploid yeastcarrying a met− auxotrophic mutation were plated onpetri plates lacking methionine (Met), five coloniesgrew. You would expect cells in which the originalmet− mutation was reversed (by a base change back tothe original sequence) would grow on the media lackingmethionine, but some of these apparent reversions couldbe due to a mutation in a different gene that somehowsuppresses the original met− mutations. How wouldyou be able to determine if the mutations in your fivecolonies were due either to a precise reversion of theoriginal met− mutation or to the generation of a suppressor mutation in a gene on another chromosome?
- Suppose you are a research assistant ina lab studying DNA-binding proteins. You have been giventhe amino acid sequences of all the proteins encoded bythe genome of a certain species and have been asked to findcandidate proteins that could bind DNA. What type of aminoacids would you expect to see in the DNA-binding regions ofsuch proteins? Explain your thinking.Homozygosity for extremely rare mutations in a humangene called SCN9A cause complete insensitivity topain (congenital pain insensitivity or CPA) and a totallack of the sense of smell (anosmia). The SCN9A geneencodes a sodium channel protein required for transmission of electrical signals from particular nerves inthe body to the brain. The failure to feel pain is a dangerous condition as people cannot sense injuries.The SCN9A gene has 26 exons and encodes a1977-amino acid polypeptide. Consanguineous matings in three different families have resulted in individuals with CPA/anosmia. In Family 1, a G-to-Atransition in exon 15 results in a truncated protein that is898 amino acids long; in Family 2, deletion of a singlebase results in a 766-amino acid polypeptide; and inFamily 3, a C-to-G transversion in exon 10 yields a458-amino acid protein.a. Hypothesize as to how each of the three SCN9Amutations affects gene structure: Why are truncatedproteins made in each case? b. How would you…Over a period of several years, a large hospital kepttrack of the number of births of babies displaying thetrait achondroplasia. Achondroplasia is a very rareautosomal dominant condition resulting in dwarfismwith abnormal body proportions. After 120,000births, it was noted that 27 babies had been born withachondroplasia. One physician was interested in determining how many of these dwarf babies resultedfrom new mutations and whether the apparent mutation rate in this geographical area was higher thannormal. He looked up the families of the 27 dwarfbirths and discovered that four of the dwarf babieshad a dwarf parent. What is the apparent mutationrate of the achondroplasia gene in this population? Isit unusually high or low?
- . Geneticists interested in human hemoglobins havefound a very large number of mutant forms. Some ofthese mutant proteins are of normal size (but haveamino acid substitutions) while others are short, dueto deletions or nonsense mutations. The first extralong example was named Hb Constant Spring, inwhich the β-globin has all of its normal amino acidsplus several extra amino acids attached after thenormal C-terminal end of the protein. a. What is the most plausible explanation forits origin?b. Is it possible that Hb Constant Spring arose fromfailure to splice out an intron?c. Estimate how many extra amino acids mightbe added to the C terminal end of the mutantprotein. The physicist Stephen Hawking, famous for his theories about black holes, has lived past the age of 70 withamyotrophic lateral sclerosis (ALS), a paralyzing neurodegenerative disease that is usually fatal at a muchyounger age. Recently, geneticists discovered that amajor cause of ALS is the unusual expansion of ahexanucleotide repeat (5′-GGGGCC-3′) that lieswithin a gene called C9ORF72, at a location outside ofthe gene’s open reading frame (ORF). A single expanded allele is sufficient to cause ALS, but the reasonthe disease allele is dominant remains unclear. Someexperimental results support the theory that the allelemakes a toxic RNA containing the expanded repeat. Ifthis theory is correct, in what ways is the mutant ALScausing allele similar to the mutant allele that causesHuntington disease? In what ways is it similar to themutant allele that causes fragile X syndrome?A+ 70°F, a cell cultue is able to graw and divide farever, but after a new mutation is found in the čeus, and the cells are at 99°F, mey Stop dividing after a few generahons.what * 16 ikery disiupted by the mutation for the cells to stop dividing after a few gener ution when Compared to the 70°F when they diide and qrow indefinitely! grown they aure 95°F grown at
- Some exons in the human genome are quite small (lessthan 75 bp long). Identification of such “microexons” isdifficult because these distances are too short to reliablyuse ORF identification or codon bias to determine ifsmall genomic sequences are truly part of an mRNAand a polypeptide. What techniques of “gene finding”can be used to try to assess if a given region of 75 bpconstitutes an exon?One histone modification that is seen consistently inmany species is the addition of an acetyl group to thetwelfth lysine in the H4 protein. If you were a geneticist working on yeast and had a clone of the H4 gene,what could you do to test whether the acetylation atthis specific lysine was necessary for the functioningof chromatin?Give two different reasons for the much higher ratioof total DNA to protein-encoding DNA in the humangenome as compared to bacterial genomes.