Michael Yudell - Welcome to the Genome

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2 FOREWARD: STILL, THE GENOMIC REVOLUTION

3 ACKNOWLEDGMENTS

4 INTRODUCTION: WELCOME BACK TO THE GENOME REFERENCES

5 1 From Mendel to Molecules IN THE ABBEY GARDEN IN THE FLY ROOM EUGENICS—“PREVAILING SPEEDILY OVER THE LESS SUITABLE” “A VERITABLE ‘AVALANCHE’ OF NUCLEIC‐ACID RESEARCH” A STRUCTURAL MILESTONE REFERENCES

6 2 The Building Blocks of Gene Sequencing RESEARCH MILESTONE 1 : INVENTION OF DNA SEQUENCING TOOLS RESEARCH MILESTONE 2 : DECIPHERING THE GENETIC CODE RESEARCH MILESTONE 3 : SYNTHESIZING DNA RESEARCH MILESTONE 4 : SEEING GENES RESEARCH MILESTONE 5 : COPYING DNA RESEARCH MILESTONE 6 : SEQUENCING A VIRAL GENOME RESEARCH MILESTONE 7: THE ULTIMATE DNA COPYING TOOL REFERENCES

7 3 Sequencing the Genome FROM GENE TO GENOME THE SEQUENCE RACING TO THE FINISH REFERENCES

8 4 The Next Generation NEXT GENERATION SEQUENCING HOW MANY GENES DO HUMANS REALLY HAVE? REFERENCES

9 5 Making the Genome Safe A SHAMEFUL PAST PREPARING FOR THE GENOME WHAT CAN RESEARCHERS, UNIVERSITIES, AND COMPANIES DO WITH YOUR GENETIC MATERIAL? THE ETHICS OF DTC GENETIC TESTING WHO OWNS YOUR GENES? MONITORING OUR GENOMIC FUTURE PREPARING THE WORLD FOR CRISPR THE BUSINESS OF BIOLOGY NATURE/NURTURE REFERENCES

10 6 The Meanings of Genetic Diversity: Part I A ROGUES’ GALLERY OF COMPLETED HUMAN GENOMES ASSESSING HUMAN VARIATION USING GENOMES NEXT GENERATION SEQUENCING USING TARGETED CAPTURE OUR GENOMIC PLACE IN THE WORLD REFERENCES

11 7 The Meanings of Genetic Diversity: Part II THE HUMAN GENOME PROJECT AND HUMAN GENETIC DIVERSITY THE STRANGE CAREER OF SCIENTIFIC RACISM UNDERMINING THE RACE CONCEPT THE HUMAN GENOME PROJECT AND THE FUTURE OF RACE CONTINUED MISSTEPS OR A PATH TO THE FUTURE? REFERENCES

12 8 The Tree of Life: 4 Billion Years of Divergence INHERITING A CONTROVERSY THE TREE OF LIFE COMPARATIVE GENOMICS BIODIVERSITY AND GENOMICS REFERENCES

13 9 Sequencing the Small and Infamous: A Look at Metagenomics and Microbiomes WHOLE‐GENOME SEQUENCING HELPS IDENTIFY DANGEROUS MUTATIONS MORE THAN ONE GENOME AT A TIME: MICROBIAL ECOLOGY, METAGENOMICS, AND MICROBIOMES OMES EVERYWHERE REFERENCES

14 10 The World to Come: Agriculture GMOs: THE BASICS RECENT CHANGES IN GENE‐BASED TECHNOLOGY FOR GENETIC MODIFICATION SYNTHETIC BIOLOGY A PLATE FULL OF GM FOODS TRENDS IN ECONOMIC USE OF GM FOODS ISSUES AND ETHICS: THE FOOD CHAIN AND UNINTENDED EFFECTS LABELING GM FOODS CHANGING ATTITUDES TOWARD GM FOOD REFERENCES

15 Conclusion: Conclusion: Don’t Believe the Hype (Including Ours) REFERENCES

16 INDEX

17 End User License Agreement

1 Chapter 10Table 10.1 GMO transformation methods adapted from Husaini et al. (2010).Table 10.2 Transgene introgression. (Adapted from Ellstrand et al., 2013). (61)

1 f06 Figure I.1 The 40‐foot Barosaurus welcomes visitors every day to the America... Figure I.2 This artist’s conception of a DNA double helix was displayed in t...

2 Chapter 1 Figure 1.1 This picture, known as a karyotype, is a photograph of all 46 hum... Figure 1.2 The nucleus of every human cell (the large purple mass inside the... Figure 1.3 Although it took decades for Gregor Mendel’s work on pea plants t... Figure 1.4 Mendel’s first law of segregation says that alleles will segregat... Figure 1.5 Most Drosophilia look like the red‐eyed fly on the left. Morgan’s... Figure 1.6 Morgan’s experiments with Drosophila led to the development of th... Figure 1.7 This eugenic map shows an estimate, state by state, of the number... Figure 1.8 James Watson and Francis Crick are seen here at Cambridge Univers... Figure 1.9 Once called the “dark lady” by her colleague Maurice Wilkins, Ros... Figure 1.10 Franklin’s X‐ray crystallography of DNA, shown to James Watson w... Figure 1.11 This diagram shows the double helix structure of DNA. In the mod... Figure 1.12 The mechanisms of epigenetics.

3 Chapter 2 Figure 2.1 This figure shows the way in which amino acids are the building b... Figure 2.2 Frederick Sanger played a critical role in the development of mol... Figure 2.3 Proteins are made in two steps. Messenger RNA first assembles alo... Figure 2.4 DNA hybridization occurs when a single strand of a double helix f...

4 Chapter 3 Figure 3.1 Sickle‐cell anemia is caused by a mutation in DNA that causes the...Figure 3.2 This test helps screen for red–green color blindness. If you don’...Figure 3.3 This chart shows, year by year, the rapid pace in growth of gene ...Figure 3.4 To the untrained eye, the vast code of our DNA is baffling. This ...Figure 3.5 Studying model organisms, including the zebrafish, Caenorhabditis...Figure 3.6 The NHGRI and Celera sequencing methods were different in one key...

5 Chapter 4Figure 4.1 Chart of Moore’s Law and actual cost.Figure 4.2 Four sequencing reactions (G, A, T, C) showing signal where a com...Figure 4.3 Single Molecule Real Time (SMRT) sequencing pin. The pin has inse...Figure 4.4 A Single Molecule Real Time (SMRT) cell showing inner workings of...Figure 4.5 Detecting base details of sequencing reactions in Single Molecule...Figure 4.6 Schematic diagram of shotgun sequencing process. The top figure s...Figure 4.7 DNA sequences of short oligonucleotides for a DNA resequencing ch...

6 Chapter 5Figure 5.1 A group of distinguished scientists and policy makers, including ...Figure 5.2 Genetic imperfections are often in the eyes of the beholder.

7 Chapter 6Figure 6.1 J. Craig Venter (left); Carl von Linne (right).Figure 6.2 A schematic diagram of what random breeding and crossing over doe...Figure 6.3 DNA sequences of the β‐globin gene of sickle‐cell (two bottom) an...Figure 6.4 From reference 39. The horizontal colored bars indicate ancestry ...

8 Chapter 7Figure 7.1 If you look closely at the two sequences of DNA above, from ident...Figure 7.2 Morton’s ideas about Native American and African inferiority were...

9 Chapter 8Figure 8.1 The changing Bacteria tree of life. Black branches represent cult...Figure 8.2 Phylogenetic tree of human, chimp, mouse, opossum, and lizard. No...Figure 8.3 Cactus (right) and euphorb (left).Figure 8.4 The three possible ways to arrange human, chimp, and mouse. The r...Figure 8.5 Tree of life indicating relationships of Archaea (A), Bacteria (B...Figure 8.6 Figure of the tree of life labeled for the three major domains of...Figure 8.7 The origin of plastids in Plantae via a cyanobacterial primary en...Figure 8.8 Amino acid sequences of chimp human and mouse.Figure 8.9 The mouse and human genomes are so much alike that the human geno...Figure 8.10 Diagnostics for DNA barcoding for two species (A and B). The red...Figure 8.11 An example of the similarity approach to barcoding.

10 Chapter 9Figure 9.1 Venn diagram showing overlap of genes in three genomes. The numbe...Figure 9.2 The figure shows a summary plot of some of the first results from...

11 Chapter 10Figure 10.1 It took many millennia of breeding by peoples in the Americas to...Figure 10.2 When engineered with a desired stretch of DNA, the common soil b...Figure 10.3 Gene target for editing.Figure 10.4 Pew Report, “The New Food Fights: U.S. Public Divides Over Food ...Figure 10.5 The NAS committee on the safety of genetically engineered food e...

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