Chapter 9 Bio 02
Which of the following processes is not thought to contribute to diversity in the genome of human individuals? (a) exon shuffling (b) single-nucleotide polymorphisms (c) CA repeats (d) duplication and deletion of large blocks of sequence
(a) exon shuffling
Which of the following statements about gene families is false? (a) Because gene duplication can occur when crossover events occur, genes are always duplicated onto homologous chromosomes. (b) Not all duplicated genes will become functional members of gene families. (c) Whole genome duplication can contribute to the formation of gene families. (d) Duplicated genes can diverge in both their regulatory regions and their coding regions.
(a). Regions of homology between nonhomologous chromosomes will cause gene duplications onto a different chromosome (as well as chromosome rearrangements).
Which of the following statements is false? (a) The human genome is more similar to the orangutan genome than it is to the mouse genome. (b) A comparison of genomes shows that 90% of the human genome shares regions of conserved synteny with the mouse genome. (c) Primates, dogs, mice, and chickens all have about the same number of genes. (d) Genes that code for ribosomal RNA share significant similarity in all eucaryotes but are much more difficult to recognize in archaea.
(d). The gene that codes for the small subunit of ribosomal RNA is conserved in all living species.
Which of the following generalities about genomes is true? (a) All vertebrate genomes contain roughly the same number of genes. (b) All unicellular organisms contain roughly the same number of genes. (c) The larger an organism, the more genes it has. (d) The more types of cell an organism has, the more genes it has.
(a) All vertebrate genomes contain roughly the same number of genes.
The nucleotide sequences between individuals differ by 0.1%, yet the human genome is made up of about 3 × 109 nucleotide pairs. Which of the following statements is false? (a) In most human cells, the homologous autosomes differ from each other by 0.1%. (b) All changes between human individuals are single-nucleotide polymorphisms. (c) Any two individuals (other than identical twins) will generally have more than 3 million genetic differences in their genomes. (d) Much of the variation between human individuals was present 100,000 years ago, when the human population was small.
(b) All changes between human individuals are single-nucleotide polymorphisms.
The puffer fish, Fugu rubripes, has a genome that is one-tenth the size of mammalian genomes. Which of the following statements is not a possible reason for this size difference? (a) Intron sequences in Fugu are shorter than those in mammals. (b) Fugu lacks the repetitive DNA found in mammals. (c) The Fugu genome seems to have lost sequences faster than it has gained sequences over evolutionary time. (d) Fugu has lost many genes that are part of gene families.
(d) Fugu has lost many genes that are part of gene families.
Which of the following functions do you not expect to find in the set of genes found in all organisms on Earth? (a) DNA replication (b) DNA repair (c) protein production (d) RNA splicing
(d). Not all organisms have introns and therefore not all organisms will have genes involved in RNA splicing.
Which of the following statements about the human genome is false? (a) More than 40% of the human genome is made up of mobile genetic elements. (b) More of the human genome codes for intron sequences than for exon sequences. (c) About 1.5% of the human genome codes for exons. (d) The exons are mainly what is conserved between the genomes of humans and other mammals.
(d). Only 3.5% of the human genome is highly conserved with other mammalian genomes, yet only about 1.5% of the human genome codes for exons.
You are studying a gene that has four exons and can undergo alternative splicing. Exon 1 has two alternatives, exon 2 has five alternatives, exon 3 has three alternatives, and exon 4 has four alternatives. If all possible splicing combinations were used, how many different splice isoforms could be produced for this gene? (a) 22 (b) 30 (c) 60 (d) 120
(d).2×5×3×4=120.
Which of the following statements is true? (a) The intron structure of most genes is conserved among vertebrates. (b) The more nucleotides there are in an organism's genome, the more genes there will be in its genome. (c) Because the fly Drosophila melanogaster and humans diverged from a common ancestor so long ago, a gene in the fly will show more similarity to another gene from the same species than it will to a human gene. (d) An organism from the same Order will be more likely to have genomes of the same size than will a more evolutionarily diverged animal.
(a). There is no necessary correlation between genome size and gene number (choice (b)). There are some fly genes, particularly those with a conserved function, that show much greater similarity to human genes than to another fly gene (choice (c)). Genome size does not necessarily correlate with evolutionary relatedness (choice (d)).
In humans and in chimpanzees, 99% of the Alu retrotransposons are in corresponding positions. Which of the following statements below is the most likely explanation for this similarity? (a) The Alu retrotransposon is not capable of transposition in humans. (b) Most of the Alu sequences in the chimpanzee genome underwent duplication and divergence before humans and chimpanzees diverged. (c) The Alu retrotransposons are in the most beneficial position in the genome for primates. (d) The Alu retrotransposons must also be in the same position in flies.
(b) Most of the Alu sequences in the chimpanzee genome underwent duplication and divergence before humans and chimpanzees diverged.
The number of distinct protein species found in humans and other organisms can vastly exceed the number of genes. This is largely due to ______________. (a) protein degradation (b) alternative splicing (c) homologous genes (d) mutation
(b). Alternative splicing can produce several different mRNA transcripts from a single gene, and these transcripts can be translated into several different but related proteins. Choices (c) and (d) do not yield more protein species than genes. Protein degradation (choice (a)) can produce several proteins from a single gene, but this mechanism is used sparingly.
The yeast genome was sequenced more than 10 years ago, yet the total number of genes continues to be refined. The sequencing of closely related yeast species was important for validating the identity of short (less than 100 nucleotides long) open reading frames (ORFs) that were otherwise difficult to predict. What is the main reason that these short ORFs are hard to find? (a) The human genome does not have short ORFs. (b) The short ORFs code for RNAs. (c) Many short stretches of DNA may, by random chance, not have a stop codon, making it difficult to distinguish those that code for proteins from those that do not. (d) Short ORFs occur mainly in gene-rich regions, making them difficult to identify by computer programs.
(c) Many short stretches of DNA may, by random chance, not have a stop codon, making it difficult to distinguish those that code for proteins from those that do not.
What is the most likely explanation of why the overall mutation rates in bacteria and in humans are roughly similar? (a) Cell division needs to be fast. (b) Most mutations are silent. (c) There is a narrow range of mutation rates that offers an optimal balance between keeping the genome stable and generating sufficient diversity in a population. (d) It benefits a multicellular organism to have some variability among its cells.
(c) There is a narrow range of mutation rates that offers an optimal balance between keeping the genome stable and generating sufficient diversity in a population. ( Choice (b) is true but cannot explain the similar mutation rate. )
The average size of a protein in a human cell is about 430 amino acids, yet the average gene in the human genome is 27,000 nucleotide pairs long. Explain
In the human genome, the exons are relatively short, whereas the introns can be quite large. A protein 430 amino acid residues long will need less than 1300 nucleotides to code for it. Furthermore, many genes in the human genome undergo alternative splicing, so some of those 27,000 nucleotides may be coding for alternative exons that are not used every time the gene is transcribed.
Transposable elements litter the genomes of primates, and a few of them are still capable of moving to new regions of the genome. If a transposable element jumped into an important gene in one of your cells when you were a baby and caused a disease, is it likely that your child would also have the disease? Explain.
It is not likely that child would have the disease, because it is unlikely that the mutation is carried in the germ line. Probably the mutation occurred in a cell that gave rise to somatic cells and not germ cells. Only mutations in germ cells are passed on to progeny.
The human genome has 3.2 × 109 nucleotide pairs. At its peak, the Human Genome Project was generating raw nucleotide sequences at a rate of 1000 nucleotides per second. At the rate of 1000 nucleotides per second, how long would it take to generate 3.2 × 109 nucleotides of sequence?
It would take more than a year (approximately 370 days). 60 seconds/minute means 8640 seconds in a day. At peak rate, you can only obtain 8,640,000 nucleotides per day.
For each of the following sentences, fill in the blanks with the best word or phrase in the list below. Not all words or phrases will be used; use each word or phrase only once. Most variation between individual humans is in the form of __________________. __________________ may arise by recombination within introns and can create proteins with novel combinations of domains. Scientists and government regulators must be very careful when introducing herbicide-resistant transgenic corn plants into the environment, because if resistant weeds arise from __________________ then the herbicides could become useless. Families of related genes can arise from a single ancestral copy by __________________ and subsequent __________________. divergence exon shuffling gene duplication horizontal gene transfer purifying selection single-nucleotide polymorphisms synteny unequal crossing-over
Most variation between individual humans is in the form of *single-nucleotide polymorphisms*. *Exon shuffling* may arise by recombination within introns and can create proteins with novel combinations of domains. Scientists and government regulators must be very careful when introducing herbicide-resistant transgenic corn plants into the environment, because if resistant weeds arise from *horizontal gene transfer* then the herbicides could become useless. Families of related genes can arise from a single ancestral copy by *gene duplication* and subsequent *divergence*.
It is thought that all eucaryotes all have about 300 genes in common. Would you predict that these genes would be used at different times during the life cycle of multicellular animals? Explain your answer.
No, these genes are likely to be involved in basic cellular functions such as DNA replication and protein production, and in the basic functions of eucaryotic cells such as the functioning of the nucleus and the movement of items between cellular compartments. Genes involved in basic cellular functions are likely to be used all the time in an organism's life and are not likely to be activated at a specific stage of life. The genes found in all eucaryotes were probably found in the promordial eucaryotic cells.
Explain how ESTs are identified and how they aid in finding the genes within an organism's genome.
To identify expressed sequence tags, or ESTs, mRNA must first be isolated from cells. This mRNA is converted into complementary DNA (cDNA) with the use of specialized nucleic acid polymerases. The nucleotide sequence of a short region of each cDNA is then determined. Each short sequence (or EST) corresponds to a portion of a gene that was expressed in the cells from which the mRNA was isolated; each sequence can be used as a tag to identify or manipulate the gene from which it came. A collection of ESTs can be input into a computer to search for matches to the total genome sequence and can thereby identify the sequences and chromosomal locations of many genes.
Your friend discovered a new multicellular organism living under the polar ice caps, and brought it back to the laboratory, where it seems to be growing well. Your friend is particularly interested in the proteins that allow this organism to survive in extreme cold. Because he is interested in proteins and because he has learned that most of the human genome does not code for exons, he is considering sequencing expressed sequence tags from this organism. What do you think the pitfalls of this approach might be? Explain.
Although expressed sequence tags (ESTs) can be very useful in identifying genes, the use of ESTs in this case may not work for several reasons. Two of these are: 1. ESTs are made from mRNAs, and thus represent actively transcribed genes. Your friend is studying the proteins that permit survival in extreme cold. Since the organism is no longer living in the extreme cold, the genes required for survival may no longer be expressed. 2. Because ESTs are made from mRNAs and because genes can be expressed at different levels, you will sequence the EST from genes that are abundantly transcribed more often than those that may be transcribed rarely.
Which of the following statements is false? (a) A mutation that arises in a mother's somatic cell often causes a disease in her daughter. (b) All mutations in an asexually reproducing single-celled organism are passed on to progeny. (c) In an evolutionary sense, somatic cells exist only to help propagate germ-line cells. (d) A mutation is passed on to offspring only if it is present in the germ line.
Choice (a) is false. Mutations are carried in the genetic material, and the only genetic material passed along to the offspring of a sexually reproducing organism comes from a germ-line cell (not a somatic cell).
Propose a reason to explain why highly repetitive regions of the genome are particularly susceptible to expansions and contractions in number.
Highly repetitive regions of the genome are particularly susceptible to unequal genetic exchange during homologous recombination.
For each of the following sentences, fill in the blanks with the best word or phrase in the list below. Not all words or phrases will be used; use each word or phrase only once. Sexual reproduction in a multicellular organism involves specialized reproductive cells, called __________________s, which come together to form a __________________ that will divide to produce both reproductive and __________________ cells. A point mutation in the DNA is considered a __________________ mutation if it changes a nucleotide that leads to no phenotypic consequence; a point mutation is considered __________________ if it changes a nucleotide within a gene and causes the protein to be non-functional. common, gamete, homologous, deleterious, unequal, somatic, neutral, intron, cellulose, zygote
Sexual reproduction in a multicellular organism involves specialized reproductive cells, called *gametes*, which come together to form a *zygote* that will divide to produce both reproductive and *somatic* cells. A point mutation in the DNA is considered a *neutral* mutation if it changes a nucleotide that leads to no phenotypic consequence; a point mutation is considered *deleterious* if it changes a nucleotide within a gene and causes the protein to be non-functional.
You are working in a human genetics laboratory that studies causes and treatments for eye cataracts in newborns. This disease is thought to be caused by a deficiency in the enzyme galactokinase, but the human gene that encodes this enzyme has not yet been identified. At a talk by a visiting scientist, you learn about a strain of baker's yeast that contains a mutation called gal1- in its galactokinase gene. Because this gene is needed to metabolize galactose, the mutant strain cannot grow in galactose medium. Knowing that all living things evolved from a common ancestor and that distantly related organisms often have homologous genes that perform similar functions, you wonder whether the human galactokinase gene can function in yeast. Because you have an optimistic temperament, you decide to pursue this line of experimentation. You isolate mRNA gene transcripts from human cells, use reverse transcriptase to make complementary DNA (cDNA) copies of the mRNA molecules, and ligate the cDNAs into circular plasmid DNA molecules that can be stably propagated in yeast cells. You then transform the pool of plasmids into gal1- yeast cells so that each cell receives a single plasmid. What will happen when you spread the plasmid-containing cells on Petri dishes that contain galactose as a carbon source? How can this approach help you find the human gene encoding galactokinase?
On galactose medium, the original gal1- yeast cells cannot grow, nor can cells that received plasmids containing most human cDNA sequences. However, yeast cells that received a plasmid with the human galactokinase gene will probably be able to grow on galactose medium and produce many progeny. This kind of "selection" procedure is very powerful, because even if only 1 in 100,000 cells has the ability to grow under particular conditions it will be easy to find it. The other 99,999 cells will die in the Petri dish and will therefore be invisible to the investigator. Indeed, scientists have found that the human galactokinase gene can function perfectly well in yeast and thus can "rescue" the defect of the gal1- mutant. It was initially astonishing that genes from humans can function properly in yeast, but this phenomenon has now been observed for many genes.
Which of the following statement about pseudogenes is false? (a) Pseudogenes code for microRNAs. (b) Pseudogenes share significant nucleotide similarity with functional genes. (c) Pseudogenes are no longer expressed in the cell. (d) There are estimated to be approximately 20,000 pseudogenes in the human genome.
(a) Pseudogenes code for microRNAs
Which of the following regions of the genome is the least likely to be conserved over evolutionary time? (a) the upstream regulatory region of a gene that encodes the region conferring tissue specificity (b) the upstream regulatory region of a gene that binds to RNA polymerase (c) the portion of the genome that codes for proteins (d) the portion of the genome that codes for RNAs that are not translated into protein
(a) the upstream regulatory region of a gene that encodes the region conferring tissue specificity
Your friend works in a lab that is studying why a particular mutant strain of Drosophila grows an eye on its wing. Your friend discovers that this mutant strain of Drosophila is expressing a transcription factor incorrectly. In the mutant Drosophila, this transcription factor, which is normally expressed in the primordial eye tissue, is now misexpressed in the wing primordial wing tissue, thus turning on transcription of the set of genes required to produce an eye in the wing primordial tissue. If this hypothesis is true, which of the following types of genetic change would most likely lead to this situation? (a) a mutation within the transcription factor gene that leads to a premature stop codon after the third amino acid (b) a mutation within the transcription factor gene that leads to a substitution of a positively charged amino acid for a negatively charged amino acid (c) a mutation within an upstream enhancer of the gene (d) a mutation in the TATA box of the gene
(c). A mutation within an upstream enhancer of the gene will affect the regulation of gene expression. Mutations within the coding sequence (choices (a) and (b)) will lead to a mutated protein being produced in the proper tissues at the proper time. A mutation in the TATA box of the gene will probably lead to no expression at all (choice (d)).
Which of the following changes is least likely to arise from a point mutation in a regulatory region of a gene? (a) a mutation that changes the time in an organism's life during which a protein is expressed (b) a mutation that eliminates the production of a protein in a specific cell type (c) a mutation that changes the subcellular localization of a protein (d) a mutation that increases the level of protein production in a cell
(c). Information for the subcellular localization of a protein is usually encoded within the translated portion of the gene.
Alternative exons can arise through the duplication and divergence of existing exons. What type of mutation below would be least tolerated during the evolution of a new exon? (a) a nucleotide change of A to G (b) a deletion of three consecutive bases. (c) mutation of the first nucleotide in the intron (d) a nucleotide change that alters a TT dinucleotide to AA
(c). The first two nucleotides in the intron are critical for signaling the exon- intron boundary; changing them would make the exon unable to be properly spliced.
Match the type of phenotypic change below with the type of genetic change most likely to cause it. Each type of genetic change may be used more than once, or may not be used at all. Phenotypic changes: 1. A protein normally localized in the nucleus is now localized in the cytoplasm. _________ 2. A protein acquires a DNA binding domain. _________ 3. Tandem copies of a gene are found in the genome._________ 4. A copy of a bacterial gene is now found integrated on a human chromosome. _________ 5. A protein becomes much more unstable. _________ 6. A protein normally expressed only in the liver is now expressed in blood cells. _________ Types of genetic change: A. mutation within a gene B. gene duplication C. mutation in a regulatory region D. exon shuffling E. horizontal gene transfer
1—A; 2—D; 3—B; 4—E; 5—A; 6—C
For each statement below, indicate whether it is true or false and explain why. A. To meet a challenge or develop a new function, evolution essentially builds from first principles, designing from scratch, to find the best possible solution. B. Nearly every instance of DNA duplication leads to a new functional gene. C. A pseudogene is very similar to a functional gene but cannot be expressed because of mutations. D. Most genes in vertebrates are unique, and only a few genes are members of multigene families. E. Horizontal transfer is very rare and thus has had little influence on the genomes of bacteria.
A. *False*. Evolution can work only by tinkering with the tools and materials on hand, not by starting from scratch to make completely new genes or pathways. New functions arise from the ancestral functions by a process of gradual mutational change, and thus may not represent the best possible solution to a problem. B. *False*. Many duplications are subsequently lost or become pseudogenes, and only a few evolve into new genes. C. *True*. Pseudogenes look very similar to normal genes but cannot produce a full-length protein, as a result of one or more disabling mutations. D. *False*. A large proportion of the genes in vertebrates (and many other species) are members of multigene families. E. *False*. By some estimates, 20% of the genomic DNA in some bacterial species arose by horizontal gene transfer.
For each statement below, indicate whether it is true or false and explain why. A. All highly conserved stretches of DNA in the genome are transcribed into RNA. B. To find functionally important regions of the genome, it is more useful to compare species whose last common ancestor lived 100 million years ago rather than 5 million years ago. C. Most mutations and genome alterations have neutral consequences. D. Proteins required for growth, metabolism, and cell division are more highly conserved than those involved in development and in response to the environment. E. Introns and transposons tend to slow the evolution of new genes.
A. *False.* Many highly conserved stretches of DNA are not transcribed but instead contain information critical for regulating where and when genes are expressed. B. *True*. Species that diverged recently have many identical stretches of DNA sequence by chance, whereas sequence similarity between species that diverged long ago is probably due to functional constraints. The sequences that are necessary to preserve the function of the gene will not be able to undergo changes and thus are more likely to be similar between species that diverged long ago. C. *True*. Most genomic changes do not alter the amino acid sequence of proteins or the regulatory properties of genes. Even some mutations that cause minor alterations have little effect on protein function. D. *True*. All organisms need to perform a similar basic set of fundamental functions, such as those for metabolism, protein synthesis, and DNA replication. Proteins involved in these functions are shared by descent, and their evolution is constrained. Different species and cells are likely to require different developmental paths and to encounter different environmental challenges, so the proteins involved in these processes will tend to be more variable. For example, bacteria do not undergo elaborate developmental programs and so lack many of the regulators of development found in eucaryotes. E. *False*. Introns and transposons can act as sites where recombinational crossovers occur. Transposons can also catalyze genetic rearrangements. Rearrangements occurring within these sequences are less likely to be detrimental than those occurring elsewhere in the genome. In general, only the short intron sequences required for splicing are important to intron function; alterations in sequences outside the splicing sites may have no consequences for intron function and thus will not be subject to purifying selection.
For each statement below, indicate whether it is true or false and explain why. A. The increased complexity of humans compared with flies and worms is largely due to the vastly larger number of genes in humans. B. Repeats of the CA dinucleotide are useful for crime investigations and other forensic applications. C. Most single-nucleotide polymorphisms cause no observable functional differences between individual humans. D. There is little conserved synteny between human and mouse genes. E. The differences between multicellular organisms are largely explained by the different kinds of genes carried on their chromosomes.
A. *False.* The number of genes differs only by about a factor of two. It is thought that the increased complexity of humans is due largely to differences in when and where the genes are expressed. Differences in the timing of splicing may also be a major contributor to the relative complexity of humans. B. *True.* There are CA repeats in many locations throughout the genome. Because the number of repeats at a given location varies greatly between individuals and families, it can be used as an identifying characteristic to match two samples (such as blood samples) from the same or related individuals. C. *True.* Nearly all single-nucleotide polymorphisms have no effect on the appearance or behavior of the individual, but a few cause important differences. D. *False.* Human and mouse chromosomes show extensive synteny, with blocks of chromosomal DNA exhibiting homologous genes arranged in the same order between the two species. E. *False.* Multicellular organisms are built from essentially the same toolbox of gene building blocks, but the parts are put together differently because of regulatory differences that dictate when and where and how much of each protein is made. Alternative splicing can also have an important role, as it can generate several proteins from a single gene in some species, yet the homologous gene in other species may produce only one protein.
The genomes of some vertebrates are much smaller than those of others. For example, the genome of the puffer fish Fugu is much smaller than the human genome, and even much smaller than those of other fish, primarily because of the small size of its introns. A. Describe a mechanism that might drive evolution toward small introns or loss of introns and could therefore account for the evolutionary loss of introns according to the "introns early" hypothesis. B. Describe a mechanism that might drive evolution toward more or larger introns and could thereby account for the evolutionary appearance of introns according to the "introns late" hypothesis.
A. Spontaneous deletions or selection pressure to decrease the time or cost of DNA replication may cause a loss of introns. B. Acquisition of intron sequences provides a selective advantage for those organisms that experience transposon insertions. According to this idea, introns became sinks for transposon and virus insertion to protect the rest of the genome. Alternatively, introns may provide another advantage to the host genome: by providing ample sites for crossing-over, larger introns could facilitate exon shuffling and thus the generation of new genes with novel functions.
A. When a mutation arises, it can have three possible consequences: beneficial to the individual, selectively neutral, or detrimental. Order these from most likely to least likely. B. The spread of a mutation in subsequent generations will, of course, depend on its consequences to individuals that inherit it. Order the three possibilities in part A to indicate which is most likely to spread and become over represented in subsequent generations, and which is most likely to become under-represented or disappear from the population.
A. The order is selectively neutral, detrimental, beneficial. Most nucleotide changes in the genome, or mutations, will have little or no effect on the fitness of the individual because many changes are not located in regions that encode a protein or regulate the expression of a gene. Even changes within a coding region may not change the amino acid encoded or may cause a conservative amino acid change, for example from one small nonpolar amino acid to another. Most changes that have a functional consequence will interfere with the regulation of a gene or the behavior of the encoded protein, usually rendering it useless and occasionally making it harmful or yielding a new function. Only very rarely will a mutation improve the performance of the gene or its encoded protein. B. The order is beneficial, selectively neutral, detrimental. Individuals bearing beneficial mutations will be more likely to have more offspring than others in the population, and thus the beneficial mutations will become over-represented in the population in subsequent generations. Individuals bearing detrimental mutations will be likely to have fewer children and grandchildren, and thus these mutations will be culled from the population, although perhaps not eliminated.
Some types of gene are more highly conserved than others. For each of the following pairs of gene functions, choose the one that is more likely to be highly conserved. A. genes involved in sexual reproduction / genes involved in sugar metabolism B. DNA replication / developmental pathways C. hormone production / lipid synthesis
A. sugar metabolism B. DNA replication C. lipid synthesis These pathways or phenomena are fundamental to the growth and proliferation of all cells, including bacteria, and thus are likely to be highly conserved from species to species.
Which of the following would contribute most to successful exon shuffling? (a) shorter introns (b) a haploid genome (c) exons that code for more than one protein domain (d) introns that contain regions of similarity to one another
Choice (d) is the correct answer. Exon shuffling is facilitated by long introns (thus choice (a) is incorrect) and by short exons that each code for one protein domain (thus choice (c) is incorrect). Because exon shuffling can occur by recombination between introns, introns with regions of similarity to one another will facilitate shuffling. A haploid genome will probably be less prone to exon shuffling than a diploid genome (thus choice (b) is incorrect), because having two copies of each gene allows an organism to keep one copy of the gene as a backup while it shuffles the other copy.
Consider a gene with a particular function. Mutation X and mutation Y each cause defects in the function of the encoded protein, yet a gene containing both mutations X and Y encodes a protein that works even better than the original protein. The odds are exceedingly small that a single mutational event will generate both mutations X and Y. Explain a simple way that an organism with a mutant gene containing both mutations X and Y could arise during evolution.
The simplest way to evolve the new gene is by duplication and divergence. If the gene is duplicated, then the cell or lineage can maintain one functional, intact old copy of the original gene and can thus tolerate the disabling mutations in the other copy. The other copy can first be modified by the X or Y mutation that impairs its function; second, at some later time, the gene with the single mutation can acquire the additional mutation to yield the doubly mutant X + Y gene with the new or improved function.
The spontaneous mutation rate in E. coli was determined by performing assays to test for the frequency of an AT to GC change. These assays were performed using E. coli that started out unable to produce histidine (His-) because of an inserted UGA stop codon that disrupted the region coding for an enzyme required to produce histidine. When a spontaneous mutation arose that enabled the UGA stop codon to code for tryptophan, the E. coli cells were then able to produce the enzyme required for histidine production. Would you expect a change in the spontaneous mutation rate of 1 mistake every 109 nucleotides copied if reversion of the stop codon to cysteine (instead of tryptophan) could cause the bacteria to produce histidine? Explain. (The codon table is shown in Figure Q9-13 to help you answer this question.)
There would be a twofold increase. Two different mutations could arise to change the stop codon to a codon coding for cysteine. This mutation would lead to a doubling of the observed spontaneous mutation rate from 1 in 109 to 2 in 109, in comparison with a single mutation that can change the stop codon to a codon coding for tryptophan. Because spontaneous mutations are rare, this would not be a particularly significant change.
