(BQ) Part 2 book Genetics - A conceptual approad has contents: The genetic code and translation, the genetic code and translation, control of gene expression in eukaryotes, quantitative genetics, population genetics, evolutionary genetics, cancer genetics,.... and other contents.
CHAPTER 15 The Genetic Code and Translation The spleen, an organ found in the upper abdomen, plays an important role in defense against infection Isolated congenital asplenia is an autosomal dominant condition in which children are born without a spleen [Sebastian Kaulitzki/Shutterstock.] A Child Without a Spleen T he spleen is an often underappreciated organ Brownish in color and weighing about a third of a pound, it sits in the left upper part of your abdomen, storing blood and filtering out bacteria and old blood cells The spleen is underappreciated because it’s widely believed that you can live without a spleen Indeed, many people who lose their spleen to automobile accidents and other trauma survive, although they are at increased risk of infection But a young child without a spleen is in serious trouble A small group of children are born without spleens; these kids are highly susceptible to life-threatening bacterial infections, and many die in childhood This rare disorder, known as isolated congenital asplenia (ICA), is inherited as an autosomal dominant trait Except for the absence of a spleen, children with ICA are unaffected But their immune function is severely compromised When infected with bacteria that the immune system normally eliminates, these children develop raging infections that quickly spread throughout the body Even when treated with modern antibiotics, they often die In 2013, an international team led by scientists from Rockefeller University discovered the genetic cause of ICA Using the power of DNA sequencing, they examined all the coding DNA of 23 individuals with ICA and compared their DNA sequences with those of 508 individuals with normal spleens Statistical analysis pointed to differences in one particular gene that was associated with ICA, a gene encoding ribosomal protein SA (RPSA) The RPSA protein is one of the 33 proteins that make up the small subunit of the ribosome, the organelle responsible for protein synthesis How a defect in the RPSA gene results in the absence of a spleen is not known Diseases such as ICA, which result from defective ribosomes, are referred to as ribosomopathies Many, but not all, individuals with ICA have mutations in RPSA, indicating that other genes may also be involved in the disorder The researchers found several different types of mutations in RPSA associated with ICA: some caused premature stop codons, halting translation before a functional protein could be made; one was a frameshift mutation, a change that alters the way the mRNA sequence is read during translation; others changed the amino acid sequence of the RPSA protein One interesting but unanswered question is why a defect in RPSA affects only the spleen Inherited mutations in RPSA occur in every cell of the body, and protein synthesis—carried out by ribosomes—is essential for numerous life processes, yet these mutations affect only the development of the spleen Why aren’t other organs altered? Why aren’t numerous physiological functions affected? Scientists are still studying these important questions THINK-PAIR-SHARE Propose some possible reasons why mutations in the RPSA gene affect only the spleen and not other tissues where ribosomes carry out translation What are some possible reasons that researchers might be interested in identifying the gene that causes a genetic disease such as ICA? In other words, what benefits might result from this research? solated congenital asplenia illustrates the extreme importance of translation, the process of protein synthesis, which is the focus of this chapter We begin by examining the molecular relation between genotype and phenotype Next, we study the genetic code—the instructions that specify the amino acid sequence of a protein—and then examine the mechanism of translation Our primary focus is protein synthesis in bacterial cells, but we also examine some features of this process in eukaryotic cells At the end of the chapter, we look at some additional aspects of protein synthesis I 15.1 Many Genes Encode Proteins The first person to suggest the existence of a relation between genotype and proteins was English physician Archibald Garrod In 1908, Garrod correctly proposed that genes encode enzymes, but unfortunately, his theory made little impression on his contemporaries Not until the 1940s, when George Beadle and Edward Tatum examined the genetic basis of biochemical pathways in the bread mold Neurospora, did the relation between genes and proteins become widely accepted Beadle and Tatum’s work helped define the relation between genotype and phenotype by leading to the one gene, one enzyme hypothesis, the idea that each gene encodes a separate enzyme THINK-PAIR-SHARE Question The One Gene, One Enzyme Hypothesis Beadle and Tatum used Neurospora to study the biochemical results of mutations Neurospora is easy to cultivate in the laboratory, and the main vegetative part of the fungus is haploid, which allows the effects of otherwise recessive mutations to be easily observed (Figure 15.1) Wild-type Neurospora grows on minimal medium, which contains only inorganic salts, nitrogen, a carbon source such as sucrose, and the vitamin biotin The fungus can synthesize all the biological molecules that it needs from these basic compounds However, mutations may arise that disrupt fungal growth by destroying the fungus’s ability to synthesize one or more essential biological molecules These nutritionally deficient mutants, termed auxotrophs (see Chapter 9), cannot grow on minimal medium, but they can grow on medium that contains the substance that they are no longer able to synthesize Beadle and Tatum first irradiated spores of Neurospora to induce mutations (Figure 15.2) Then they placed the spores in different culture tubes with complete medium (medium containing all the biological substances needed for growth) These spores grew into fungi and produced spores by mitosis Next, they transferred spores from each culture to tubes containing minimal medium Fungi with auxotrophic mutations did not grow on the minimal medium, which allowed Beadle and Tatum to identify cultures that possessed mutations Once they had determined that a particular culture had an auxotrophic mutation, Beadle and Tatum set out to determine the specific effect of the mutation They transferred spores of each mutant strain from complete medium to a series of tubes (see Figure 15.2), each of which contained minimal medium plus one of a variety of essential biological molecules, such as an amino acid If the spores in a tube grew, Beadle and Tatum were able to identify the added substance as the biological molecule whose synthesis had been affected by the mutation For example, an auxotrophic mutant that would grow only on minimal medium to which arginine had been added must have possessed a mutation that disrupts the synthesis of arginine 15.1 Beadle and Tatum used the fungus Neurospora, which has a complex life cycle, to work out the relation of genes to proteins [Namboori B Raju, Stanford University.] 15.2 Beadle and Tatum developed a method for isolating auxotrophic mutants in Neurospora Adrian Srb and Norman H Horowitz patiently applied this procedure to genetically dissect the multistep biochemical pathway of arginine synthesis (Figure 15.3) They first isolated a series of auxotrophic mutants whose growth required arginine Then they tested these mutants for their ability to grow on minimal medium supplemented with three compounds: ornithine, citrulline, and arginine From the results, they were able to place the mutants into three groups on the basis of which of the substances allowed growth (Table 15.1) Based on these results, Srb and Horowitz proposed that the biochemical pathway leading to the amino acid arginine has at least three steps: They concluded that the mutations in group I affect step of this pathway, mutations in group II affect step 2, and mutations in group III affect step But how did they know that the order of the compounds in the biochemical pathway was correct? Notice that if step is blocked by a mutation, then the addition of either ornithine or citrulline allows growth because these compounds can still be converted into arginine (see Figure 15.3) Similarly, if step is blocked, the addition of citrulline allows growth, but the addition of ornithine has no effect If step is blocked, the spores will grow only if arginine is added to the medium The underlying principle is that an auxotrophic mutant cannot synthesize any compound that comes after the step blocked by a mutation Using this reasoning with the information in Table 15.1, we can see that the addition of arginine to the medium allows all three groups of mutants to grow Therefore, biochemical steps affected by all the mutants precede the step that results in arginine The addition of citrulline allows group I and group II mutants to grow, but not group III mutants; therefore, group III mutations must affect a biochemical step that takes place after the production of citrulline but before the production of arginine: TABLE 15.1 Growth of arginine auxotrophic mutants on minimal medium with various supplements Mutant Strain Ornithine Citrulline Arginine Group I + + + Group II − + + Group III − − + Note: A plus sign (+) indicates growth; a minus sign (−) indicates no growth 15.3 Method used to determine the relation between genes and enzymes in Neurospora The biochemical pathway shown here leads to the synthesis of arginine in Neurospora Steps in the pathway are catalyzed by enzymes affected by mutations The addition of ornithine allows the growth of group I mutants, but not group II or group III mutants; thus, mutations in groups II and III affect steps that come after the production of ornithine We’ve already established that group II mutations affect a step before the production of citrulline; so group II mutations must block the conversion of ornithine into citrulline: Chapter 22 Ada, G L., and G Nossal 1987 The clonal-selection theory Scientific American 257(2): 62–69 A history and review of the development of the theory of clonal selection Bebelein, B., D J McKay, and R S Mann 2004 Direct integration of Hox and segmentation gene inputs during Drosophila development Nature 431:653–659 Reports on research showing that Hox genes interact with segmentation genes in Drosophila development Carroll, S B., B Prud’homme, and N Gompel 2008 Regulating evolution Scientific American 298(5): 60–67 An excellent review of how the alteration of gene expression can lead to major evolutionary changes Chan, Y F., M E Marks, F C Jones, et al 2010 Adaptive evolution of pelvic reduction in sticklebacks by recurrent deletion of Pitx1 enhancer Science 327:302–305 Research on the regulatory element that controls loss of pelvic spines in threespine sticklebacks De Robertis, E M 2008 Evo-devo: variations on ancestral themes Cell 132:185– 186 Explains how a common set of genes in the Bilateria control development Fernald, R D 2006 Casting a genetic light on the evolution of eyes Science 313:1914–1918 A great review article on the evolution of eye development Gellert, M 1992 Molecular analysis of V( D) J recombination Annual Review of Genetics 22:425–446 An extensive review of the molecular mechanism of somatic recombination in genes of the immune system Gellert, M 2002 V(D)J recombination: RAG proteins, repair factors, and regulation Annual Review of Biochemistry 71:101–132 A review of the mechanism of recombination that leads to antibody diversity Jan, Y N., and L Y Jan 1998 Asymmetrical cell division Nature 392:775–778 A review of the mechanisms by which asymmetrical cell division, which plays a critical role in development, arises Jung, D., and F W Alt 2004 Unraveling V( D) J recombination: insights into gene regulation Cell 116:299–311 A good review of the history of our understanding of somatic recombination in genes of the immune system, with current information about mechanisms *Kolata, G 1998 Clone: The Road to Dolly and the Path Ahead New York: William Morrow A readable and accurate account of the cloning of Dolly, the first mammal cloned from an adult cell, and the ethical debate generated by this experiment Leder, P 1982 The genetics of antibody diversity Scientific American 247(5): 102–115 A review of the processes that lead to diversity in antibodies Lemons, D., and W McGinnis 2006 Genomic evolution of Hox gene clusters Science 313:1918–1922 A good review of Hox gene clusters and how they differ among animals McKinnell, R G., and M A Di Berardino 1999 The biology of cloning: history and rationale BioScience 49:875–885 A good summary of the history of cloning and some of its practical uses Pennisi, E., and G Vogel 2000 Clones: a hard act to follow Science 288:1722– 1727 A news report on the different organisms that have been successfully cloned Raff, M 1998 Cell suicide for beginners Nature 396:119–122 An introduction to the process of apoptosis Reik, W 2007 Stability and flexibility of epigenetic gene regulation in mammalian development Nature 447:425–432 A discussion of the importance of epigenetic changes in mammalian development Science 1998 Volume 281, issue 5381 Contains a number of articles on apoptosis Shapiro, M D., M, E Marks, C L Peiche, et al 2004 Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks Nature 428:717–723 Research on the evolution of reduced pelvic spines in threespine stickleback fish Simpson, G G., and C Dean 2002 Arabidopsis, the Rosetta Stone of flowering time Science 296:285–289 A good review of the genetic basis of flowering time in plants Soshnikova, N., and D Duboule 2009 Epigenetic temporal control of mouse Hox genes in vivo Science 324:1320–1323 Reports on research indicating that the temporal sequence of gene expression in Hox genes is controlled by directional changes in chromatin structure Teng, G., and F N Papavasiliou 2007 Immunoglobulin somatic hypermutation Annual Review of Genetics 41:107–120 A detailed review of the process of somatic hypermutation Thompson, G B 1995 Apoptosis in the pathogenesis and treatment of disease Science 267:1456–1462 A discussion of the role of apoptosis in disease Unniraman, S., and D G Schatz 2007 Strand-biased spreading of mutations during somatic hypermutation Science 317:1227–1230 A discussion of the mechanism of somatic hypermutation Vogel, G 2013 Human stem cells from cloning, finally Science 340:795 A report of the therapeutic cloning of human embryos Weaver, D T., and F W Alt 1997 From RAGs to stitches Nature 388:428–429 Reviews findings concerning the mechanism of V- D- J joining in the generation of antibody diversity Yamamoto, Y., D W Stock, and W R Jeffrey 2004 Hedgehog signaling controls eye degeneration in blind cavefish Nature 431:844–847 A research report on the genetic basis of eye loss Chapter 23 Bittner, M., P Meltzer, Y Chen, et al 2000 Molecular classification of cutaneous malignant melanoma by gene expression profiling Nature 406:536–540 Presents evidence of genes that affect the spread of cancer The Cancer Genome Atlas Research Network 2011 Integrated genomic analysis of ovarian carcinoma Nature 474:609–615 Results of recent genomic analysis of ovarian cancer The Cancer Genome Atlas Research Network 2012 Comprehensive molecular portraits of human breast tumours Nature 490:61–70 A genomic analysis of breast cancer tumors Chang, T C., D Yu, Y S Lee, et al 2008 Widespread microRNA repression by Myc contributes to tumorigenesis Nature Genetics 40:43–50 Reports that Myc, a protein produced by an oncogene, affects the expression of microRNAs Chen, J., R M McKay, and L F Parada 2012 Malignant glioma: lessons from genomics, mouse models, and stem cells Cell 149:36–47 Discusses results of genomic studies of malignant gliomas Chin, L., and J W Gray 2008 Translating insights from the cancer genome into clinical practice Nature 452:553–563 A review of how information from cancer genomic studies can be used in the treatment of cancer See also other articles in this issue of Nature on the use of molecular techniques to better diagnose and treat cancer Dawson, M A., and T Kouzarides 2012 Cancer epigenetics: from mechanism to therapy Cell 150:12–27 An in-depth review of epigenetic changes associated with cancer Fearon, E R., and B Vogelstein 1990 A genetic model for colorectal tumorigenesis Cell 61:759–767 A review of some of the mutations that lead to colorectal cancer Fodde, R., and R Smits 2002 A matter of dosage Science 298:761–763 A discussion of haplodeficiency in tumor-suppressor genes Gibbs, W W 2003 Untangling the roots of cancer Scientific American 289(1): 56– 65 A good review of some views of cancer, including the genomic instability hypothesis Gruber, S B., N A Ellis, K K Scott, et al 2002 BLM heterozygosity and the risk of colorectal cancer Science 297:2013 A survey showing that carriers of the tumor-suppressor gene for Bloom syndrome have increased risk of cancer Gudmundsson, J., P Sulem, A Manolescu, et al 2007 Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24 Nature Genetics 39:631–637 An example of the power of genomic approaches to identifying genes that contribute to cancer Gundem, G., P Van Loo, B Kremeyer, et al 2015 The evolutionary history of lethal metastatic prostate cancer Nature 520:353–362 Research demonstrating that metastatic prostate tumors are often established by cells from multiple clones within the primary tumor and from other metastatic tumors Hanahan, D., and R A Weinberg 2000 The hallmarks of cancer Cell 100:57–70 A review of the different types of genes that are associated with cancer Hernando, E., Z Nahlé, G Juan, et al 2004 Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control Nature 430:797–802 A report on the role the RB protein plays in genomic instability Hung, R J., J D McKay, V Gaborieau, et al 2008 A susceptibility locus for lung cancer maps to nicotine acetylcholine receptor subunit genes on 15q25 Nature 452:633–641 Reports that genome-wide association studies have detected genes that predispose some people to lung cancer induced by smoking Jager, N., M Schlesner, D T W Jones, et al 2013 Hypermutation of the inactive X chromosome is a frequent event in cancer Cell 155:567–581 Demonstration and interpretation of high rates of mutation on the inactive X chromosome in tumor cells Knudson, A G 2000 Chasing the cancer demon Annual Review of Genetics 34:1– 19 A short history of the search for a genetic cause of cancer, along with a review of hereditary cancers and the genes that cause them Kumar, M., J Lu, K L Mercer, et al 2007 Impaired microRNA processing enhances cellular transformation and tumorigenesis Nature Genetics 39:673– 682 A report on research showing that global reduction in microRNAs increases tumor progression Ledford, H 2010 The cancer genome challenge Nature 465:972–974 A news article on current efforts to sequence the genomes of cancer cells Lengauer, C 2003 An unstable liaison Science 300:442–443 A discussion of the role of DNA methylation in cancer Lengauer, C., K W Kinzler, and B Vogelstein 1998 Genetic instabilities in human cancer Nature 396:643–649 A review of how defects in DNA repair and chromosome-segregation genes lead to cancer Ma, L., J Teruya-Feldstein, and R A Weinberg 2007 Tumour invasion and metastasis initiated by microRNA-10b in breast cancer Nature 449:682–688 A report on the role of microRNAs in breast cancer Massague, J 2004 G1 cell-cycle control and cancer Nature 432:298–306 A comprehensive review of cell cycle control at the G1/S checkpoint Minn, A J., G P Gupta, P M Siegel, et al 2005 Genes that mediate breast cancer metastasis to lung Nature 436:518–524 A report on the detection of genes having roles in the metastasis of breast-tumor cells to the lung Orr-Weaver, T L., and R A Weinberg 1998 A checkpoint on the road to cancer Nature 392:223–224 A discussion of how mutations that affect cell cycle checkpoints may contribute to cancer progression Peifer, M., F Hertwig, and F Roels 2015 Telomerase activation by genomic rearrangements in high-risk neuroblastoma Nature 526:700–704 Research showing that chromosome rearrangements and other mutations that activate telomerase play an important role in high-risk neuroblastoma Pogue-Geile, K L., R Chen, M P Bronner, et al 2006 Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism PLoS Medicine 3:2216–2228 A report on research showing that a mutation in the palladin gene is associated with the spread of pancreatic cancer Ponder, B A., 2001 Cancer genetics Nature 411:336–341 A good review of the types of genetic events that contribute to cancer Science articles on breast cancer 2014 Science 343:1451–1475 A series of articles on breast cancer on the 10-year anniversary of the cloning of BRCA1 Seligson, D B., S Horvath, T Shi, et al 2005 Global histone modification patterns predict risk of prostate cancer recurrence Nature 435:1262–1270 Reports that histone acetylation and methylation are associated with the chances of prostate cancer reappearing Steeg, P S 2007 Micromanagement of metastasis Nature 449:671–673 A short review of the role of miRNAs in metastasis Stratton, M R., P J Campbell, and P A Futreal 2009 The cancer genome Nature 458:719–724 A short review of genomic studies of mutations that cause cancer Weizman, J B., and M Yaniv 1999 Rebuilding the road to cancer Nature 400:401 A discussion of the first successful attempt to convert normal human cells into cancer cells by artificially introducing telomerase-expressing genes, oncogenes, and tumor-suppressor genes into a cell Chapter 24 Allen, H L., K Estrada, G Lettre, et al 2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height Nature 467:832–838 A report of a very large genome-wide association study of human height involving data from over 183,000 individuals Barton, N H 1989 Evolutionary quantitative genetics: how little we know? Annual Review of Genetics 23:337–370 A review of how quantitative genetics is used to study the process of evolution Beltrao, P., G Cagney, and N J Krogan 2010 Quantitative genetic interactions reveal biological modularity Cell 141:739–745 A review of how genetic interactions affect quantitative traits Buckler, E S., J B Holland, P J Bradbury, et al 2009 The genetic architecture of maize flowering time Science 325:714–718 Reports on the identification of QTLs that affect flowering time in corn Cunningham, P 1991 The genetics of thoroughbred horses Scientific American 264(5): 92–98 An interesting account of how quantitative genetics is being applied to the breeding of thoroughbred horses Dudley, J W 1977 76 generations of selection for oil and protein percentage in maize In E Pollak, O Kempthorne, and T B Bailey, Jr., Eds Proceedings of the International Conference on Quantitative Genetics, pp 459–473 Ames: Iowa State University Press A report on the progress of one of the longest-running selection experiments East, E M 1910 A Mendelian interpretation of variation that is apparently continuous American Naturalist 44:65–82 East’s interpretation of how individual genes acting collectively produce continuous variation, including a discussion of Herman Nilsson-Ehle’s research on kernel color in wheat East, E M 1916 Studies on size inheritance in Nicotiana Genetics 1:164–176 East’s study of flower length in Nicotiana Falconer, D S., and T F C MacKay (Contributor) 1996 Introduction to Quantitative Genetics, 4th ed New York: Addison-Wesley An excellent basic textbook on quantitative genetics Frary, A., T C Nesbitt, S Grandillo, et al 2000 A quantitative trait locus key to the evolution of tomato fruit size Science 289:85–88 A report on the discovery and cloning of one QTL that is responsible for the quantitative difference in fruit size between wild tomatoes and cultivated varieties Freathy, R M., D O Mook-Kanamori, U Sovio, et al 2010 Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight Nature Genetics 42:430–435 Analysis of genome-wide association studies that located genes influencing birth weight in humans Fridman, E., F Carrari, Y S Liu, et al 2004 Zooming in on a quantitative trait for tomato yield using interspecific introgression Science 305:1786–1789 A research report on the use of QTL analysis to locate a gene that plays an important role in sugar yield in tomatoes Gillham, N W 2001 Sir Francis Galton and the birth of eugenics Annual Review of Genetics 2001:83–101 A history of Galton’s contributions to the eugenics movement Glazier, A M., J H Nadeau, and T J Aitman 2002 Finding genes that underlie complex traits Science 298:2345–2349 A discussion of some of the methods used to find genes affecting complex quantitative traits and what standards should exist to establish the influence of genes on QTLs Jones, P., K Chase, A Martin, et al 2008 Single-nucleotide-polymorphism-based association mapping of dog stereotypes Genetics 178:1033–1044 A report on research using genome-wide association studies to locate genes that affect size and behavioral traits in dogs Mackay, T F C 2001 The genetic architecture of quantitative traits Annual Review of Genetics 35:303–339 A review of techniques for QTL mapping and results from studies on QTLs Martienssen, R 1997 The origin of maize branches out Nature 386:443–445 A discussion of the identification of QTLs that contributed to the domestication of corn Moore, K J., and D L Nagle 2000 Complex trait analysis in the mouse: the strengths, the limitations, and the promise yet to come Annual Review of Genetics 43:653–686 A review of the genetic analysis of complex characteristics in mice, particularly emphasizing those that are medically important Nordborg, M., and D Weigel 2008 Next generation genetics in plants Nature 456:720–723 A review article on the use of genome-wide association studies to find genes that affect quantitative traits in plants Paterson, A H., E S Lander, J D Hewitt, et al 1988 Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms Nature 335:721–726 A report on a study identifying QTLs that control fruit mass, pH, and other important characteristics in tomatoes Plomin, R 1999 Genetics and general cognitive ability Nature 402:C25–C29 A good discussion of the genetics of general intelligence and the search for QTLs that influence it Song, X., W Huang, M Shi, et al 2007 A QTL for rice grain width and weight encodes a previously unknown RING-type E3 ubiquitin ligase Nature Genetics 39:623–630 Reports on the use of QTL mapping to locate a gene that plays an important role in rice grain shape Tian, F., P J Bradbury, P J Brown, et al 2011 Genome-wide association study of leaf architecture in the maize nested association mapping population Nature Genetics 43:159–168 Study of QTLs for leaf architecture in corn Van Laere, A., M Nguyen, M Braunschweig, et al 2003 A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig Nature 425:832– 836 A research report on a gene associated with increased muscle mass in pigs Wright, S I., I V Bi, S G Schroeder, et al 2005 The effects of artificial selection on the maize genome Science 308:1310–1314 Describes the use of single-nucleotide polymorphisms to better understand how corn was domesticated Zheng, P., W B Allen, K Roesler, et al 2008 A phenylalanine in DGAT is a key determinant of oil content and composition in maize Nature Genetics 40:367– 372 A research report on a gene that controls increased oil production in corn Zimmer, C 2008 The search for intelligence Scientific American 299(4): 68–75 A readable account of research that is attempting to locate genes that influence intelligence in humans Chapter 25 Buri, P 1956 Gene frequency in small populations of mutant Drosophila Evolution 10:367–402 Buri’s report on his well-known experiment demonstrating the effects of genetic drift on allelic frequencies Hardy, G H 1908 Mendelian proportions in a mixed population Science 28:49–50 An original paper by Godfrey Hardy outlining the Hardy–Weinberg law Hartl, D L., and A G Clark 2006 Principles of Population Genetics, 4th ed Sunderland, Mass: Sinauer Associates An advanced textbook in population genetics Hedrick, P H 2009 Genetics of Populations 4th ed Sudbury, Mass.: Jones and Bartlett Another advanced population genetics textbook Hedrick, P W., R O Peterson, L M Vucetich, et al 2014 Genetic rescue in Isle Royale wolves: genetic analysis and the collapse of the population Conservation Genetics 15:1111–1121 A genetic study of the wolves of Isle Royale Saccheri, I., M Kuussaari, M Kankare, et al 1998 Inbreeding and extinction in a butterfly metapopulation Nature 392:491–494 A discussion of the role of inbreeding in population extinction of butterflies Sheridan, E., J Wright, N Small, et al 2013 Risk factors for congenital anomaly in a multiethnic birth cohort: an analysis of the Born in Bradford study Lancet 382:1350–1359 A study of over 11,000 babies born in Bradford, Great Britain, between 2007 and 2011; the study found that birth anomalies were twice as likely in children born to first-cousin parents than to parents who were unrelated Chapter 26 Barluenga, M., K N Stolting, W Salzburger, et al 2006 Sympatric speciation in Nicaraguan crater lake cichlid fish Nature 439:719–722 A research report on evidence that sympatric speciation arose in cichlid fish inhabiting Lake Apoyo in Nicaragua Coltman, D W., P O’Donoghue, J T Jorgenson, et al 2003 Undesirable evolutionary consequences of trophy hunting Nature 426:655–658 A research report on the effects of trophy hunting on horn size in bighorn sheep Coyne, J A., and H A Orr 2004 Speciation Sunderland, Mass.: Sinauer Associates An excellent book on all aspects of speciation Egan, S P., G J Ragland, L Assour, et al 2015 Experimental evidence of genomewide impact of ecological selection during early stages of speciation-with-geneflow Ecology Letters 18:817–825 Research involving artificial selection and genome sequencing of apple and hawthorn races of Rhagoletis pomonella Forbes, A A., T H Powell, L L Stelinski, et al 2009 Sequential sympatric speciation across trophic levels Science 323:776–779 A research report on sympatric speciation in wasps that parasitize host races of the apple maggot fly Rhagoletis pomonella Lamichhaney, S., J Berglund, M S Almen, et al 2015 Evolution of Darwin’s finches and their beaks revealed by genome sequencing Nature 518:371–375 Genome sequencing of Darwin’s finches Nei, M., and S Kumar 2000 Molecular Evolution and Phylogenetics Oxford: Oxford University Press An advanced textbook on the methods used in the study of molecular evolution Pigeon, G., M Festa-Bianchet, D W Coltman, et al 2016 Intense selective hunting leads to artificial evolution in horn size Evolutionary Application 9:521–530 Research on the evolution of horn size in bighorn sheep Roca, A L., N Georgiadis, J Pecon-Slattery, et al 2001 Genetic evidence for two species of elephant in Africa Science 293:1473–1477 Reports on a study in which the use of DNA sequencing shows that two different species of elephant live in Africa Sato, A., H Tichy, C O'hUigin, et al 2001 On the origin of Darwin’s Finches Molecular Biology and Evolution 18:299–311 Reports on research using a molecular clock to estimate the time of origin of Darwin’s finches from a common ancestor Takahata, N 2007 Molecular clock: an anti-neo-Darwinian legacy Genetics 176:1– A historical account of the development of the idea of the molecular clock Thompson, J D 1991 The biology of an invasive plant BioScience 41:393–401 A good summary of how Spartina anglica evolved through polyploidy Vilá, C., P Savolainen, J E Maldonado, et al 1997 Multiple and ancient origins of the domestic dog Science 276:1687–1689 A report on the use of the molecular clock and mitochondrial DNA sequences to estimate that the dog was domesticated more than 100,000 years ago Wooding, S 2006 Phenylthiocarbamide: a 75 year adventure in genetics and natural selection Genetics 172:2015–2023 An interesting and entertaining account of the history of the PTC taste polymorphism Wooding, S., B Bufe, C Grassi, et al 2006 Independent evolution of bitter-taste sensitivity in humans and chimpanzees Nature 440:930–934 A report on research demonstrating that PTC taster alleles evolved independently in humans and chimpanzees ... UAA, UAG, and UGA are termination (stop) codons As we learned in Chapter 14, tRNAs serve as adapter molecules that bind particular amino acids and deliver them to a ribosome, where the amino acids... (see Chapter 7), they were able to demonstrate that mutations affecting any one step in a pathway always occurred at the same chromosomal location Beadle and Tatum reasoned that mutations affecting... for translation and all 20 amino acids A different amino acid was radioactively labeled in each of the 20 tubes Radioactive protein appeared in only one of the tubes—the one containing labeled