Deck 22: Population and Evolutionary Genetics

Question 1

An unexpected outcome
A newborn screening program identified a baby with a rare autosomal recessive disorder called arginosuccinate aciduria (AGA), which causes high levels of ammonia to accumulate in the blood. Symptoms usually appear in the first week after birth and can progress to include severe liver damage, developmental delay, and mental retardation. AGA occurs with a frequency of about 1 in 70,000 births. There is no history of this disorder in either the father's or mother's family. The above case raises several questions:
Since it appears that the unaffected parents are heterozygotes, would it be considered unusual that there would be no family history of the disorder? How would they be counseled about risks to future children?

Answer 1

In rare autosomal recessive disorders like Arginosuccinate aciduria (AGA), the parents are mostly heteorzygotes or carriers and are unaffected. The parents though may not express the trait may have the recessive allele received from their fore generations. The homozygous recessive alleles are often masked and may not express in the immediate generations. Hence, sometimes family history of the genetical disorder may not be available.
The recessive allele received from both the parents' results in the affected child though there is no enough evidence of family history of the disorder. The disorder can be detected in the first week of the birth and exhibit the symptoms like severe liver damage, developmental delay and mental retardation. The disorder occurs at a frequency of about 1 in 70,000 births. The disorder can be screened through genetic testing of the fetus. The unaffected parents should undergo the genetic testing to know whether they carry the recessive allele or not. If carrying the recessive allele the parents should follow the prompt advice of the counselor to avoid the risk of having an affected child.

Question 2

Population geneticists study changes in the nature and amount of genetic variation in populations, the distribution of different genotypes, and how forces such as selection and drift act on genetic variation to bring about evolutionary change in populations and the formation of new species. From the explanation given in the chapter, what answers would you propose to the following fundamental questions?
(a) How do we know how much genetic variation is in a population?
(b) How do geneticists detect the presence of genetic variation as different alleles in a population?
(c) How do we know whether the genetic structure of a population is static or dynamic?
(d) How do we know when populations have diverged to the point that they form two different species?
(e) How do we know the age of the last common ancestor shared by two species?

Answer 2

The percentage of genetic variation in a population can be observed by analyzing the levels of amino acid and nucleotides in the genes. It is also possible to identify genetic variation by observing phenotypic variations in a population.
Geneticists detect genetic variation by considering order of bases in the nucleotides in genes and by identifying variation levels of enzymes through the process of protein electrophoresis.
(c)Genetic structure of a population is always dynamic, which is brought by the mechanism of genetic variation.
(d)The genetic divergence can be identified at the point at which the gene flow between two species is decreased, by which one population may no longer interbreed with other group of species.
The divergence of population reflects the action of natural selection and genetic drift. The genetic variation in the group of species may carry considerable differences in alleles or allele frequencies at different loci of the chromosome. The allele frequencies will be homogenized among the species during migration of individuals between the populations. The emergence of migration leads to genetic divergence in the population.
(e)The analysis of mitochondrial Deoxyribonucleic acid (DNA) is useful to determine the last common ancestor shared by two divergent species.

Question 3

An unexpected outcome
A newborn screening program identified a baby with a rare autosomal recessive disorder called arginosuccinate aciduria (AGA), which causes high levels of ammonia to accumulate in the blood. Symptoms usually appear in the first week after birth and can progress to include severe liver damage, developmental delay, and mental retardation. AGA occurs with a frequency of about 1 in 70,000 births. There is no history of this disorder in either the father's or mother's family. The above case raises several questions:
If the disorder is so rare, what is the frequency of heterozygous carriers in the population?

Answer 3

In rare autosomal recessive disorders like Arginosuccinate aciduria (AGA), the parents are mostly heteorzygotes or carriers and are unaffected. The arginosuccinate aciduria is resulted due to deficiency of the arginosuccinic acid lyase enzyme that metabolizes the arginosuccinic acid. The enzyme is encoded by two functional alleles. When the both alleles are non-functional then it will lead to the disorder. Heterozygotes may have one copy of functional and other non-functional allele. When the child receives the non-functional copy of the allele from both the parents the child is affected. The heterozygous parents have 25% of chance to produce an affected child each time. There are 50% of chances to be as carriers and 25% of chances to produce normal child.

Question 4

Review the chapter concepts list on page 441. All these pertain to the principles of population genetics and the evolution of species. Write a short essay describing the roles of mutation, migration, and selection in bringing about spectiation.

Question 5

An unexpected outcome
A newborn screening program identified a baby with a rare autosomal recessive disorder called arginosuccinate aciduria (AGA), which causes high levels of ammonia to accumulate in the blood. Symptoms usually appear in the first week after birth and can progress to include severe liver damage, developmental delay, and mental retardation. AGA occurs with a frequency of about 1 in 70,000 births. There is no history of this disorder in either the father's or mother's family. The above case raises several questions:
What are the chances that two heterozygotes will meet and have an affected child?

Question 6

Price et al. (1999. J. Bacteriol. 181: 2358-2362) conducted a genetic study of the toxin transport protein (PA) of Bacillus anthracis, the bacterium that causes anthrax in humans. Within the 2294-nucleotide gene in 26 strains they identified five point mutations-two missense and three synonyms-among different isolates. Necropsy samples from an anthrax outbreak in 1979 revealed a novel missense mutation and five unique nucleotide changes among ten victims. The authors concluded that these data indicate little or no horizontal transfer between different B. anthracis strains.
(a) Which types of nucleotide changes (missense or synonyms) cause amino acid changes?
(b) What is meant by horizontal transfer?
(c) On what basis did the authors conclude that evidence of horizontal transfer is absent from their data?

Question 7

The genetic difference between two Drosophila species, D. heteroneura and D. sylvestris, as measured by nucleotide diversity, is about 1.8 percent. The difference between chimpanzees ( P. troglodytes ) and humans ( H. sapiens ) is about the same, yet the latter species are classified in different genera. In your opinion, is this valid? Explain why.

Question 8

The use of nucleotide sequence data to measure genetic variability is complicated by the fact that the genes of higher eukaryotes are complex in organization and contain 5? and 3 → Flanking regions as well as introns. Researchers have compared the nucleotide sequence of two cloned alleles of the ?-globin gene from a single individual and found a variation of 1 percent. Those differences include 13 substitutions of one nucleotide for another and 3 short DNA segments that have been inserted in one allele or deleted in the other. None of the changes takes place in the gene's exons (coding regions). Why do you think this is so, and should it change our concept of genetic variation?

Question 9

Calculate the frequencies of the AA, Aa, and aa genotypes after one generation if the initial population consists of 0.2 AA , 0.6 Aa , and 0.2 aa genotypes and meets the requirements of the Hardy-Weinberg relationship. What genotype frequencies will occur after a second generation?

Question 10

Consider rare disorders in a population caused by an autosomal recessive mutation. From the frequencies of the disorder in the population given, calculate the percentage of heterozygous carriers
(a) 0.0064
(b) 0.000081
(c) 0.09
(d) 0.01
(e) 0.10

Question 11

What must be assumed in order to validate the answers in Problem 7?

Question 12

In a population where only the total number of individuals with the dominant phenotype is known, how can you calculate the percentage of carriers and homozygous recessives?

Question 13

If 4 percent of a population in equilibrium expresses a recessive trait, what is the probability that the offspring of two individuals who do not express the trait will express it?

Question 14

Consider a population in which the frequency of allele A is p = 0.7 and the frequency of allele a is q = 0.3, and where the alleles are codominant. What will be the allele frequencies after one generation if the following occurs?
(a) w AA = 1, w Aa = 0.9, and w aa = 0.8
(b) w AA = 1, w Aa =0.95, and w aa = 0.9
(c) w AA = 1, w Aa = 0.99, w aa = 0.98
(d) w AA = 0.8, w Aa = 1, w aa = 0.8

Question 15

If the initial allele frequencies are p = 0.5 and q = 0.5 and allele a is a lethal recessive, what will be the frequencies after 1, 5, 10, 25, 100, and 1000 generations?

Question 16

Under what circumstances might a lethal dominant allele persist in a population?

Question 17

Assume that a recessive autosomal disorder occurs in 1 of 10,000 individuals (0.0001) in the general population and that in this population about 2 percent (0.02) of the individuals are carriers for the disorder. Estimate the probability of this disorder occurring in the offspring of a marriage between first cousins. Compare this probability to the population at large.

Question 18

One of the first Mendelian traits identified in humans was a dominant condition known as brachydactyly. This gene causes an abnormal shortening of the fingers or toes (or both). At the time, some researchers thought that the dominant trait would spread until 75 percent of the population would be affected (because the phenotypic ratio of dominant to recessive is 3:1). Show that the reasoning was incorrect.

Question 19

Describe how populations with substantial genetic differences can form. What is the role of natural selection?

Question 20

Achondroplasia is a dominant trait that causes a characteristic form of dwarfism. In a survey of 50,000 births, five infants with achondroplasia were identified. Three of the affected infants had affected parents, while two had normal parents. Calculate the mutation rate for achondroplasia and express the rate as the number of mutant genes per given number of gametes.

Question 21

A recent study examining the mutation rates of 5669 mammalian genes (17,208 sequences) indicates that, contrary to popular belief, mutation rates among lineages with vastly different generation lengths and physiological attributes are remarkably constant (Kumar, S., and Subramanian, S. 2002. Proc. Natl. Acad. Sci. [USA] 99: 803-808). The average rate is estimated at 12.2 × 10 ?9 per bp per year. What is the significance of this finding in terms of mammalian evolution?

Question 22

A form of dwarfism known as Ellis-van Creveld syndrome was first discovered in the late 1930s, when Richard Ellis and Simon van Creveld shared a train compartment on the way to a pediatrics meeting. In the course of conversation, they discovered that they each had a patient with this syndrome. They published a description of the syndrome in 1940. Affected individuals have a short-limbed form of dwarfism and often have defects of the lips and teeth, and polydactyly (extra fingers). The largest pedigree for the condition was reported in an Old Order Amish population in eastern Pennsylvania by Victor McKusick and his colleagues (1964). In that community, about 5 per 1000 births are affected, and in the population of 8000, the observed frequency is 2 per 1000. All affected individuals have unaffected parents, and all affected cases can trace their ancestry to Samuel King and his wife, who arrived in the area in 1774. It is known that neither King nor his wife was affected with the disorder. There are no cases of the disorder in other Amish communities, such as those in Ohio or Indiana.
(a) From the information provided, derive the most likely mode of inheritance of this disorder. Using the Hardy-Weinberg law, calculate the frequency of the mutant allele in the population and the frequency of heterozygotes, assuming Hardy-Weinberg conditions.
(b) What is the most likely explanation for the high frequency of the disorder in the Pennsylvania Amish community and its absence in other Amish communities?

Question 23

List the barriers that prevent interbreeding and give an example of each.

Question 24

What are the two groups of reproductive isolating mechanisms? Which of these is regarded as more efficient, and why?

Question 25

Are there nucleotide substitutions that will not be detected by electrophoretic studies of a gene's protein product?

Question 26

In a recent study of cichlid fish inhabiting Lake Victoria in Africa, Nagl et al. (1998. Proc. Natl. Acad. Sci. [USA] 95: 14,238-14,243) examined suspected neutral sequence polymorphisms in noncoding genomic loci in 12 species and their putative river-living ancestors. At all loci, the same polymorphism was found in nearly all of the tested species from Lake Victoria, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids at other African lakes.
(a) Why would you suspect neutral sequences to be located in noncoding genomic regions?
(b) What conclusions can be drawn from these polymorphism data in terms of cichlid ancestry in these lakes?

Question 27

What genetic changes take place during speciation?

Question 28

Some critics have warned that the use of gene therapy to correct genetic disorders will affect the course of human evolution. Evaluate this criticism in light of what you know about population genetics and evolution, distinguishing between somatic gene therapy and germ-line gene therapy.

Question 29

25. Comparisons of Neanderthal mitochondrial DNA with that of modern humans indicate that they are not related to modern humans and did not contribute to our mitochondrial heritage. However, because Neanderthals and modern humans are separated by at least 25,000 years, this does not rule out some forms of interbreeding causing the modern European gene pool to be derived from both Neanderthals and early humans (called CroMagnons). To resolve this question, Caramelli et al. (2003. Proc. Natl. Acad. Sci. [USA] 100: 6593-6597) analyzed mitochondrial DNA sequences from 25,000-year-old Cro-Magnon remains and compared them to four Neanderthal specimens and a large dataset derived from modern humans. The results are shown in the graph.

The x -axis represents the age of the specimens in thousands of years; the y -axis represents the average genetic distance. Modern humans are indicated by filled squares; Cro-Magnons, open squares; and Neanderthals, diamonds.
(a) What can you conclude about the relationship between CroMagnons and modern Europeans? What about the relationship between Cro-Magnons and Neanderthals?
(b) From these data, does it seem likely that Neanderthals made any mitochondrial DNA contributions to the Cro-Magnon gene pool or the modern European gene pool?