Genetics & Society

By Charlotte Omoto and Paul Lurquin

This user friendly book explores both the classical and cutting edge aspects of genetic science. The impact of DNA technology on medicine and society at large are also investigated.

• Language: English
• Publisher: Lulu Publishing Services
• Release date: Mar 9, 2015
• ISBN: 9781483424118

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Lurquin

Copyright © 2015 Charlotte Omoto & Paul Lurquin.

All rights reserved. No part of this book may be reproduced, stored, or transmitted by any means—whether auditory, graphic, mechanical, or electronic—without written permission of both publisher and author, except in the case of brief excerpts used in critical articles and reviews. Unauthorized reproduction of any part of this work is illegal and is punishable by law.

ISBN: 978-1-4834-2712-6 (sc)

ISBN: 978-1-4834-2411-8 (e)

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Lulu Publishing Services rev. date: 02/18/2015

Contents

Preface

Acknowledgements

Chapter 1 WHAT ARE GENES?

Chapter 2 INHERITANCE OF MENDELIAN TRAITS: SINGLE GENE TRAITS

Chapter 3 MENDELIAN TRAITS IN HUMANS

Chapter 4 GENES TO PHENOTYPE

Chapter 5 MULTI-GENE NETWORKS

Chapter 6 USEFUL PRODUCTS THROUGH GENETIC ENGINEERING

Chapter 7 GENETICALLY MODIFIED PLANTS

Chapter 8 WHEN THINGS GO WRONG!

Chapter 9 TERATOGENS, MUTAGENS AND HUMAN REPRODUCTION

Chapter 10 GENETICS OF POPULATIONS

Chapter 11 KNOWLEDGE OF OUR GENOME

Chapter 12 SURVIVAL OF THE FITTEST?

Chapter 13 NATURE VERSUS NURTURE

Chapter 14 CONSERVATION GENETICS

Chapter 15 GENETICALLY MODIFIED ANIMALS

Chapter 16 GENE THERAPY

Chapter 17 EPIGENETICS

AUTHORS

Preface

This book was conceived when Charlotte Omoto taught GenCB 150, Genetics and Society at Washington State University in Pullman, WA. She tried a number of different textbooks for the course including those by Riki Lewis, a number of non-majors versions of standard genetics textbooks, and the Cartoon Book of Genetics. Although she liked the Cartoon Book of Genetics, she found that it was missing major aspects of genetics such as population and quantitative genetics. She did not find the non-majors, watered down, versions of majors genetics textbooks nor the Cartoon Book of Genetics satisfactory since they did not deal with societal aspects such as newborn genetic testing, GMO etc. Thus she used her lecture notes as the basis for a new non-majors genetics textbook. Thus readers will see that there are references to Washington State University and environs. Paul Lurquin, a genetics professor who had already established a publishing career agreed to help her with writing and getting the textbook published. Thus DNA and Genetics was published in 2004 by Columbia University Press. Now, 10 years later, some chapters are terribly out of date or have become irrelevant for non-majors. Many new topics that were unknown or just being discovered at the time are now relevant to laypeople such as whole genome sequencing with the cost of getting genetic information for an individual becoming affordable. Topics such as genetic engineering of animals which have entered the commercial market, and epigenetics are no longer esoteric topics for specialists. In the ensuing years, Omoto had developed more games that illustrate genetic principles. Charlotte Omoto taught the course with Gary Thorgaard, and he made major contributions in the area of conservation genetics and the interesting case study of genetics of Icelandic people. We felt that this was a good time to write a new book in light of the new information available.

Acknowledgements

We thank Andris Kleinhofs for reading over the whole book and providing helpful comments, particularly on the chapter on genetic engineering of plants. Gary Thorgaard, with whom Charlotte Omoto taught the course, made major contributions in the area of conservation genetics and the interesting case study of genetics of Icelandic people. He also helped in the chapter on population genetics, whole genome, and quantitative genetics. We thank Mike Skinner for his help in making sure the chapter on epigenetics was up-to-date, and accurate. We thank Neil Cox, of Moscow Idaho for drawing Figure 17.2, and Derek Pouchnick for help with Chapter 11 cover image. Finally, we thank all the students who took the course in 2011 and 2012 who made very helpful suggestions. It is for them that we strive to keep the book interesting and updated.

Chapter 1

WHAT ARE GENES?

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A) DNA in a two-dimensional word representation, B) as a double-helix and C) diagram of two DNA base pairs, the basis for copying.

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Photograph of X-ray diffraction pattern of DNA produced by Rosalind Franklin. The tell-tale sign of the X pattern of diffraction indicates that DNA has a helical structure.

DNA is the basic chemical of inheritance. In this chapter we will cover the fundamentals of DNA structure. The structure explains how it can be copied to produce future cells and generations. We are using the natural copying mechanism of cells for a wide range of purposes including forensics.

What is the chemical composition of genes?

Now, students even in middle school are taught that DNA (short for deoxyribonucleic acid) make up our genes. Experiments demonstrated that indeed this simple compound, DNA, is responsible for encoding the genes necessary for all of life. As with many ground-breaking discoveries, initially a number of well-established scientists belittled this idea, claiming that such a simple polymer couldn’t possibly encode all the information to make even simple bacteria, let alone complex organisms like humans. This chapter shows that DNA and its structure are the keys to understanding inheritance.

DNA

The Swiss biochemist Friedrich Miescher discovered what he called nuclein near the end of the 19th century. Miescher had no idea that the material he isolated as a major component of sperm and pus would be key to inheritance. Because sperm cells were tiny, it took some time before scientists realized that sperm cells were the male reproductive cells and thus must carry genetic material to form progeny individuals.

For a long time after Miescher’s discovery, DNA was thought to be a simple molecule, consisting of nucleotides strung together like beads on a string. Each nucleotide is composed of a sugar (deoxyribose) chemically linked to phosphorus atoms and one of four different nitrogenous bases, adenine, guanine, cytosine and thymine, abbreviated as A, T, G, and C. They were called nitrogenous because they contain two (in T), three (in C) to five (in A and G) nitrogen atoms.

The structure of the DNA molecule as understood at the time did not provide clues of how it could play a central role in heredity. It seemed much too simple a structure to account for the many already known hereditary traits. But then, scientists found that the building blocks of DNA -- the nucleotides -- were repeated at least hundreds of times in the DNA molecule. The DNA molecule is a very long thin structure, so easily broken in the process of isolation. But as techniques to isolate DNA from living cells improved, the number of nucleotides in a DNA molecule was found to be in the thousands, and then to hundreds of thousands and more. Scientists had discovered that DNA is a polymer, very much like many plastics such as polyethylene and polypropylene, except that DNA is a very, very long polymer with up to billions of nucleotides, As, Ts, Gs, and Cs. Yet, nobody knew what this polymer was for, nor did anyone know the fine structure of the DNA molecule.

Scientists back then thought that only animals and bacteria possessed DNA, and that plants did not have any DNA. Since plants, as well as animals and bacteria, all had well defined hereditary characteristics (for example, morphology and color of plants and animals and virulence of bacteria); DNA could not be the genetic material, so the logic went. We now know that plants do contain DNA, but because plants have tough cell walls, different techniques were needed to isolate DNA from them. Genetically plants, animals and bacteria, indeed all living things, are very similar in spite of their great diversity. This is because their hereditary properties are all based on DNA.

DNA can be specifically stained

The ability to specifically stain DNA was an important advance in learning about the chemical nature of the genetic material. In the early 1900’s histochemistry, that is staining biological material to distinguish the chemical nature of various microscopic structures, was in its heyday. In this period, German biochemist, Robert Feulgen developed a way to specifically stain DNA. He then used this method to stain DNA in different cells. The Feulgen reaction, which we still use today, specifically stains DNA purple. Feulgen used this technique on all kinds of tissues from animals, plants, and protozoa. Under the microscope, the purple DNA stain was found in a central compartment, called the nucleus (plural nuclei), of all these cells. Feulgen showed that the nuclei of these cells stained, including that of plant cell nuclei. This showed that plants had DNA, and that the DNA of cells are located in the nuclei.

Because the amount of stain was directly proportional to the amount of DNA, the amount of Feulgen stain can be used to measure the amount of DNA present in cells. Hewson Swift at the University of Chicago showed using this approach that cells from all different parts of corn plant had the same amount of DNA but the amount of DNA in pollen was half that found in other cells of the plant such as the leaf and root cells. Further, he found that rapidly dividing cells in the root tip had twice as much DNA compared to non-dividing cells. All these observation are consistent with what we expect of the genetic material (see chapter 2). If DNA was the genetic material, its amount should be same in all the cells of the organism regardless of the size of the cell, and the gametes, sperm or pollen, and egg, should contain half the genetic material. Indeed, organisms receive one half of their genetic material from a male gamete and one half from a female gamete. Finally, if cells are rapidly dividing, they would be duplicating their genetic material prior to cell division, and thus should have twice as much genetic material.

A more interesting observation using the Feulgen stain was that the stained material, DNA, assumed a characteristic shape prior to cell division. Most of the time, the Feulgen stain showed an purple blob filling the whole nucleus. But just before cells divided, the DNA formed into sausage-like structures called chromosomes, chromo = color, somes = bodies. By careful counting, it was found that the number of these chromosomes was the same in different cells of the same organism. We will cover more about the study of chromosomes in Chapter 8 and in Chapter 14.

DNA determines genetic properties in bacteria.

How can we be sure that DNA is in fact the genetic material? We needed a way to show not only that the material had characteristics we expect of the genetic material but that in fact that it directs the expression of an inherited trait. Oswald Avery used the bacterium Streptococcus pneumoniae which can cause pneumonia, to demonstrate this. His laboratory possessed two strains of these bacteria. One was a virulent strain that caused pneumonia and the other strain did not, the ‘avirulent’ strain. When bacteria grow, one cell divides into two, so each cell division results in double the number of cells. On an agar media on a petri dish, they cannot move, so a colony of bacteria grows into a mound of cells called a colony. The virulent and avirulent colonies look different on an agar media. The virulent strain appears smooth while the avirulent strain appears rough. These are two inherited characteristics: 1) the ability or inability to cause pneumonia, and 2) the appearance of the colonies on a agar plate.

So to determine the chemical nature of the genetic material, Avery wanted to transfer the hereditary properties described above between the two strains. Heating bacterial cells kills them, which, as you know, is why we cook meat such as hamburger well (over 160o F). When the smooth, virulent bacteria are heated to over 160o F, they are killed and can no longer cause pneumonia. But when these heat-killed virulent bacteria are mixed with live, rough, avirulent bacteria, the bacteria from this mixture injected into mice caused pneumonia. This was known before Avery did his research. What might we conclude from that experiment? We might hypothesize that the hereditary material from the heat-killed virulent bacteria transferred to the rough avirulent live bacteria, transforming them to become virulent. If DNA was the hereditary material, DNA from the virulent strain might be able to change the virulence of the rough avirulent strain. To test this hypothesis, Avery extracted DNA from the smooth virulent strain and mixed it with the rough avirulent strain. When the mixture with DNA-treated rough avirulent bacteria were plated on agar media, a few smooth colonies appeared in the petri dish that had mostly rough colonies. This phenomenon is called transformation. To test whether the bacteria forming the smooth colonies also acquired the trait of causing pneumonia, they were injected into mice. These mice contracted pneumonia and died! So we can interpret these results as follows: the DNA isolated from the killed smooth virulent strain transferred to the rough avirulent strain and conferred the genetic trait of virulence and the appearance of smooth colonies on a petri dish. Thus this is evidence that DNA is indeed the genetic material.

However, as solidly as the above experiment seemed to show that DNA is the genetic material, there were plenty of skeptics, especially among the established scientists. They based their skepticism on the fact that DNA has only four building blocks, A, T, G and C, and did not seem to have enough building blocks to code for all the diversity of life. In contrast, proteins, another type of polymer made of amino acid building blocks can make much more complicated structure because they can use 20 different amino acid building blocks instead of just four buildings blocks of DNA. Think about how complicated a word you can write using just four letters. Then think about how complex a sentence you can write using 20 letters.

So to further test the hypothesis that DNA was the genetic material, the purified DNA was treated with deoxyribonuclease, an enzyme that destroys DNA. The mixture of deoxyribonuclease and DNA, which presumably is destroyed, was added to the rough avirulent strain. When this was plated on agar media, no smooth colonies appeared. That is, no transformation occurred! This means that destroying DNA destroyed the ability to transform. In another experiment instead of adding deoxyribonuclease, they added protease which destroys proteins. When this mixture was plated on agar media, some smooth colonies appeared as before when no enzymes were added. If protein was the genetic material and was present in their DNA samples, proteases should have destroyed the ability of the material to transform. It did not. This meant that proteins were clearly NOT the genetic material. There it was: the genetic material --the genes— of Streptococcus pneumoniae was not made of proteins, but of DNA.

These two sets of experiments would seem to provide conclusive evidence that DNA was the genetic material. Yet, most scientists thought that protein, not DNA, was the genetic material despite all this evidence. Proteins exist in almost infinite varieties so proteins were still thought to be the genetic material. Some argued that DNA may be the genetic material of bacteria. After all, the experiment was done with bacteria, but certainly, it could not be responsible for the hereditary properties of higher life forms, such as animals and plants. Of course, the skeptics were wrong and we know that DNA is an almost universal genetic material. Genetic material of simple viruses, bacteria, plants and animals are all made of DNA. Some viruses use as genetic material a chemical very similar to DNA called ribonucleic acid (RNA) where the base thymine (T) is replaced by uracil (U) and where the sugar is ribose, not deoxyribose.

DNA is a double helix

DNA is a very long polymer made up of millions of nucleotides. Each nucleotide contains one of the four nitrogenous bases (A, T, G or C) linked to a deoxyribose unit, itself linked to a chemical group containing a phosphorus atom. DNA is held together by bonds between the phosphate and the deoxyribose units. Since deoxyribose is a type of sugar molecule, we refer to the DNA’s sugar-phosphate backbone (top title page image). One important clue to the structure and arrangement of DNA is that the amount of adenine (A) was equal to the amount of thymine (T) and the amount of guanine (G) was equal to the amount of cytidine (C). This was true for DNA from all organisms. Yet figuring out the arrangement of the DNA molecule to explain the above observation required the use of a relatively new technique called X-ray crystallography because it used X-rays on crystals of molecules. Crystals are regular arrangements of molecules. They are formed when identical molecules are packed together. This is rather simple to do for a small molecule. The first crystal structure solved by this technique was simple table salt, sodium chloride, NaCl. For example, you can make sugar crystals by putting a string into a solution saturated with sugar. This happens because the rough structure of the string initiates crystal formation. Once some sugar molecules attach to the string, other sugar molecules can fit in like bricks on a wall. X-rays can be used to elucidate the structure of a crystal. The regular arrangement of atoms in a crystal deflects X-rays, and form spots in concentric rings on a photographic film. The more organized the structure, the more spots are formed farther out in the ring. By noting the location and the intensity of these spots, scientists can determine the relative positions of the atoms in the crystal and thus determine the three-dimensional structure of the crystallized molecule.

However, large complex organic molecules such as proteins are difficult to get into an organized crystal necessary to use the technique. For example, structure of one of the smallest proteins, insulin, was not solved by this technique until 1969 by Dorothy Hodgkin, five years after she received the Nobel prize for determining the atomic structure of a number of other organic molecules. The first structure of protein, of myoglobin, was determined by Max Perutz and John Kendrew, who received Nobel Prize for Chemistry for their work in 1962. DNA is such a large molecule it does not form crystals readily. Thus the fact that Rosalind Franklin, managed to crystallize DNA in the early 1950s was a remarkable achievement. She found two different forms of DNA crystals that were mixed together. It was necessary to have only one form in a crystal so she had to work hard to purify one form and obtained the first high-quality X-ray diffraction pattern for a DNA crystal, second image of the title page.

At this time two young scientists who had not done any work with DNA before, James Watson and Francis Crick, struck up a collaboration to solve the structure of DNA. Indeed, Watson and Crick did not do a single experiment to solve the structure of DNA. They did see the X-ray crystallographic image of DNA made by Rosalind Franklin. The arrangement of the spots radiating out in an X shape immediately suggested a helical molecule to Watson. Watson convinced Crick of that interpretation, and they started building a large physical model of DNA. The image of them standing next to a model of DNA taller than them on the cover of the book Watson and Crick and DNA is famous. After a few days of trial and error, they produced a model of DNA as a helical molecule that could explain Franklin’s X-ray crystallographic image. DNA was a double helix in which the sugar-phosphate backbones are on the outside, while the bases are on the inside of the molecule (chapter title page, B). This structure was held together by weak bonds between an A with a T indicated by the dotted lines in the figure, and similarly G was held to a C. This A pairing with T and G pairing to C is called complementary base pairing (chapter title page, C). With this structure, you can see why the number of As is always equal to the number of Ts and number of Gs equal to number of Cs. The discovery of the double helical structure of DNA was published in a short report in 1953 by Watson and Crick but Rosalind Franklin was not an author on the article. She died in 1958 of ovarian cancer. In 1962, Watson, Crick, and Wilkins, Franklin’s supervising professor received the Nobel Prize.

An important feature of DNA, double helix, is that the DNA strands are anti-parallel which means that the two strands read in opposite directions. On the chapter title page A, one strands reads right side up but the opposite strand reads upside down. We use this as a way to depict this feature, and later show DNA pieces with one strand right side up and the other upside down. This will become important in many functions of DNA including copying DNA.

Copying DNA

In their 1953 article, Watson and Crick noted that it has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material. They meant by this that complementary base pairing in and of itself allows us to know the sequence of the As, Ts, Gs, and Cs on the opposite strand if we know the sequence of one strand. That is, DNA contains the information necessary to make a copy of itself. As cells multiply, the two daughter cells must contain the same genetic information as the parent cell. Thus, there must be a way to copy the DNA sequence to ensure that the genetic information in daughter cells is the same as that of the parent cell. We know that that DNA molecules must be copied accurately. When Watson and Crick deduced the double helical structure of DNA with complementary base pairing, they realized that the structure itself provided the basic mechanism for copying. The double helical structure of DNA with