Monthly Archives: September 2015

rotten > Library > Medicine > DNA How did life first get started on this planet? And why does it suck so much? The answer is found in DNA.

DNA was discovered in 1869, but at the time, no one really knew what it was or whether it was important. Scientists knew that it was a complicated molecule found inside the cells of living things, and they suspected it had something to do with heredity.

In 1944, quantum physicist Erwin Schrodinger (of "Schrodinger's Cat" fame) published a collection of lectures titled What is Life? Schrodinger postulated that all life was somehow designed according a pre-set script that could found among the molecules of the body.

Following on his discoveries in the study of subatomic systems, Schrodinger believed that information about the structure of a life form was physically encoded into the life form at a very small scale, and that the code was inherited by each generation from the previous. Schrodinger challenged his contemporaries in the life sciences to find that code.

In the 1950s, two young scientists named James Watson and Francis Crick discovered that the molecules of DNA were coiled up in the double helix formation. A couple of years later, an experiment using bacteria proved that DNA was the medium for transferring hereditary -- also called genetic -- information.

By the time you finish reading this next section, you might well think DNA stands for "Do Not Ask," but it's actually an abbreviation for deoxyribonucleic acid. DNA is a string-shaped molecule arranged as two strands spiraling around each other, connected through the middle by hydrogen atoms. The shape is known as a "double helix."

The DNA molecule is twined very tightly, so that a large number of atoms fit into a very small space. Each strand of DNA contains a number of smaller molecule-like clusters of atoms, known as nucleotides. There are four nucleotides, each usually represented by a letter -- A, T, C, or G.

From here out, everything you read is going to be pretty grossly oversimplified. The nucleotide letters are arranged into three-letter "words" known as codons. There are 64 codons, or 64 possible combinations of the four nucleotides. (There are also 64 hexagrams in the I-Ching, which may or may not be a coincidence.) Each codon is sort of like a command in computer coding -- an instruction on how to do something.

Each set of instructions is framed by a "start" and "stop" codon. These markers are like a set of parentheses. Inside the parentheses, there is one specific set of instructions, which is almost always (Make a protein.) When a new set of parentheses begin, a new instruction has been launched, such as (Make a different protein.)

These instructions are carried out by RNA, or ribonucleic acid. Here's how it works: A molecule called an enzyme bonds with DNA, and the resulting chemical reaction creates RNA. When you unstick the RNA from the DNA, the RNA carries an impression of the DNA, called a transcription.

The RNA then drops into a simmering stew of amino acids, which are the carbon-based raw materials of life. The amino acids interact chemically with the RNA segment to make proteins, in a type dictated by the information copied from the parenthetical DNA segment. Like the gears and springs in a pocket watch, proteins are the fundamental machines that do the work of life within a cell.

If your eyes are glazing over right about now, don't feel bad. It's insanely complicated. Here's an absurdly oversimplified (but surprisingly reasonable) way to think about it: DNA is like a long string of connected Legos, and RNA is like Play-Doh.

The Play-Doh (RNA) presses onto the string of Legos (DNA), which leaves an indentation in the Play-Doh. The Play-Doh gets tacky and falls away from the Legos. The now-stiff Play-Doh drops into a pile of loose Legos (amino acids). As they bang around together, appropriately shaped Legos snap into the impressions left in the Play-Doh to make a new Lego construct (a protein).

The type and number of proteins in a cell determine whether the cell is a bone cell, a blood cell, a brain cell, or a spleen cell. By following some specific combination of codons in a segment of DNA, RNA manufactures all the parts that go into a cell, and by following the entire recipe book (decoding the entire strand of DNA in the correct order and with the proper raw materials), you can incubate an entire person... or cat, dog, mouse, aardvark, bacterium, virus, fungus, sunflower or dragonfly.

So this bizarre little super-complicated molecule holds basic recipe book on how to build a human being in about eleventy million trillion easy steps. How did this come to be?

We know that the origins of DNA are the origins of life on this planet. Unfortunately knowing that and knowing the actual origins of DNA are two different things.

Experiments have demonstrated that the combination of base chemicals and environmental conditions on primitive Earth -- including lava, electrical storms, carbon and water -- were conducive to the formation of complex organic molecules. Some organic molecules formed on Earth; others may have been dropped here by passing comets or meteors. It's not quite clear how, but all these factors appear to have come together to form RNA first, then RNA eventually became more complex and developed into DNA.

There isn't really any one view about how this happened, but the earliest forms of life derived from these first building blocks. Well, according to most views, anyway. From these simple building blocks, more complex forms of life evolved through the process of mutation. Because the process described above are extremely complex and involve millions of small chemical changes, there are numerous opportunities for something to go wrong between the Legos and the Play-Doh.

Although DNA can repair itself to a certain extent, some errors persist and are inherited by the next generation of the life form in question. Over the course of a great deal of time, this eventually led to the development of opposable thumbs, tonsils and third nipples.

Although the stuff was unimaginable just 200 years ago, DNA is now a part of everyday life. Because each person inherits a unique genetic sequence, DNA has revolutionized criminal investigations by offering a not-quite infallible method of identifying suspects from the blood, semen, spit and hair they leave behind. DNA testing can be used to establish paternity within an inconsequential margin of error.

In medicine, DNA grows more prominent every day. Although the genetic code still contains mysteries, scientists have managed to unlock genetic markers for various diseases. Some diseases are directly caused by faulty DNA. Gene therapy -- in which healthy DNA is spliced onto damaged DNA -- is still in its early stages. Gene therapy shows promise in principle, but its track record in clinical trials to date isn't stellar.

Then there's genetic engineering. We may not fully understand how DNA works, or where it came from, or exactly precisely how all those little codons work, but in typical human form, we have already figured out how to monkey with them.

Genetic engineering is rampant in the U.S. food industry, including tomatoes, beets, wheat and corn. On the bright side, GE has made foods more resistant to spoilage, more easily processed, or more easily cooked. GE hybrids, whether plants or animals, are known as transgenic organisms.

In order to accomplish this goal, genetic engineers do some questionable things, like splicing fish genes onto strawberries to keep them from freezing, or splicing human genes into chickens to make them grow larger more rapidly. Some early experimentation has been done splicing human DNA into pigs in order to grow pigs with organs that can then be transplanted into humans. (Would eating bacon from these pigs constitute cannibalism?)

Much of this gene splicing is done by introducing an engineered virus into the host organism. By their nature, viruses tinker with the DNA of host cells, so the strategy has a certain logic behind it. On the other hand, if you think there's something inherently alarming about creating viruses and introducing them into animals in order to create bizarre new interspecies hybrids, you're not alone.

The ultimate frontier -- tampering with the DNA of human beings -- is just around the corner. Rumors of human cloning persist, but no proven clones have surfaced yet.

There are two predominant reasons to tamper with human DNA -- to improve the health of a living human, or to breed children with specific traits, presumably superior ones. Experiments in the former area have been hampered because patients have an annoying tendency to die. It turns out that inserting genetically engineered viruses into people and animals can be bad for their health. Who would have thought it?

Experiments in the latter field, sometimes known as eugenics, are equally troublesome. Although trials with animals have produced super-smart mice and sheep whose breast milk contains insulin, it's still relatively taboo to talk about manufacturing smart, beautiful children with an insatiable appetite for world domination.

In the old days, eugenics had to be accomplished through the cumbersome task of selective breeding, but modern geneticists are increasingly able to manipulate DNA directly to enhance qualities such as strength, resistance to disease and intelligence. Although Adolf Hitler gave eugenics a bad name during the 1940s, scientists are still plugging away to promote the practice.

Although current efforts are mostly limited to examining ways to diagnose and treat genetically transmitted diseases like cystic fibrosis and cancer, you know it won't be long before we're all battling for our lives against a generation of supermen whose genes for morality were accidentally excised by an overeager scientist trying to prevent warts.

Naturally, we won't be able to beat them. You can only hope that the technology to create these superbabies won't exist during our lifetimes... which would be fairly pointless since the technology pretty much exists already, held in check by only a rapidly fraying string of ethical posturing. After all, the last time you stopped at McDonald's, you ate a tomato with fish genes in it. Pretty much anything goes after that.

O brave new world!

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DNA - Rotten.com

DNA Structure and Function

Background History:

Mitosis in onion root tip DNA stands for deoxyribonucleic acid. DNA is pretty unusual in that it is about the only common molecule capable of directing its own synthesis.

The processes of mitosis and meiosis were discovered in the 1870s and 1890s. It was observed that, as cells divided, chromosomes moved around in a cell, and people began to wonder what their function was. It was determined that chromosomes were made of protein and DNA, about which people knew almost nothing. People began to suspect that chromosomes had something to do with genetics, but couldnt explain what/how. When enough evidence was accumulated to confirm that chromosomes did, indeed, have something to do with genetics, most people thought that in some way the protein in the chromosomes served as the genetic material. People knew that DNA was also in the chromosomes, but because its structure was unknown and people didnt know much about it, few people thought it was the genetic material.

Griffiths Experiment In 1928, Frederick Griffith performed an experiment using pneumonia bacteria and mice. This was one of the first experiments that hinted that DNA was the genetic code material. Click on the mouse button to study his experiment. He used two strains of Streptococcus pneumoniae: a smooth strain which has a polysaccharide coating around it that makes it look smooth when viewed with a microscope, and a rough strain which doesnt have the coating, thus looks rough under the microscope. When he injected live S strain into mice, the mice contracted pneumonia and died. When he injected live R strain, a strain which typically does not cause illness, into mice, as predicted they did not get sick, but lived. Thinking that perhaps the polysaccharide coating on the bacteria somehow caused the illness and knowing that polysaccharides are not affected by heat, Griffith then used heat to kill some of the S strain bacteria and injected those dead bacteria into mice. This failed to infect/kill the mice, indicating that the polysaccharide coating was not what caused the disease, but rather, something within the living cell. Since Griffith had used heat to kill the bacteria and heat denatures protein, he next hypothesized that perhaps some protein within the living cells, that was denatured by the heat, caused the disease. He then injected another group of mice with a mixture of heat-killed S and live R, and the mice died! When he did a necropsy on the dead mice, he isolated live S strain bacteria from the corpses. Griffith concluded that the live R strain bacteria must have absorbed genetic material from the dead S strain bacteria, and since heat denatures protein, the protein in the bacterial chromosomes was not the genetic material. This evidence pointed to DNA as being the genetic material. Transformation is the process whereby one strain of a bacterium absorbs genetic material from another strain of bacteria and turns into the type of bacterium whose genetic material it absorbed. Because DNA was so poorly understood, scientists remained skeptical up through the 1940s.

Hershey & Chases Experiment In 1952, Alfred Hershey and Martha Chase did an experiment which is so significant, it has been nicknamed the Hershey-Chase Experiment. Click on the virus button to study their experiment. At that time, people knew that viruses were composed of DNA (or RNA) inside a protein coat/shell called a capsid. It was also known that viruses replicate by taking over the host cells metabolic functions to make more virus. We are used to thinking and talking about viruses which invade our bodies and make us sick, but there are other, different kinds of viruses that infect other kinds of animals, still other viruses which infect plants, and even some viruses that infect bacteria. A virus which infects a bacterium is called a bacteriophage because the host bacterium cell is killed as the new virus particles leave the bacterial cell. In order to do all this, the virus must inject whatever is the viral genetic code into the host cell. Thus, people realized that the viral genetic code material had to be either its DNA or its protein capsid. Hershey and Chase sought an answer to the question, Is it the viral DNA or viral protein coat (capsid) that is the viral genetic code material which gets injected into a host bacterium cell? To try to answer this question, Hershey and Chase performed an experiment using a bacterium named Escherichia coli, or E.coli for short (named after a scientist whose last name was Escher) and a virus called T2 that is a bacteriophage that infects E.coli. Isolated T2, like other viruses, is just a crystal of DNA and protein, so it must live inside E.coli in order to make more virus like itself. When the new T2 viruses are ready to leave the host E.coli cell (and go infect others), they burst the E.coli cell open, killing it (hence the name bacteriophage). The results that Hershey and Chase obtained indicated that the viral DNA, not the protein, is its genetic code material.

Hershey and Chase used radioactive chemicals to distinguish between (label) the protein capsid and the DNA in T2 virus so they could tell which of those molecules entered the E.coli cells. Since some amino acids contain sulfur in their side chains, if T2 is grown in E.coli with a source of radioactive sulfur, the sulfur will be incorporated into the T2 protein coat making it radioactive. Since DNA has lots of phosphorus in its phosphate (PO4) groups, if T2 is grown in E.coli with a source of radioactive phosphorus, the phosphorus will be incorporated into the viral DNA, making that radioactive. Hershey and Chase grew two batches of T2 and E.coli: one with radioactive sulfur and one with radioactive phosphorus to get batches of T2 labeled with either radioactive S or radioactive P. Then, these radioactive T2 were placed in separate, new batches of E.coli, but were left there only 10 minutes. This was to give the T2 time to inject their genetic material into the bacteria, but not reproduce. In the next step, still in separate batches, the mixtures were agitated in a kitchen blender to knock loose any viral parts not inside the E.coli but perhaps stuck on the outer surface. Hopefully, this would differentiate between the protein and DNA portions of the virus. Then, each mixture was spun in a centrifuge to separate the heavy bacteria (with any viral parts that had gone into them) from the liquid solution they were in (including any viral parts that had not entered the bacteria). The centrifuge causes the heavier bacteria to be pulled to the bottom of the tube where they form a pellet, while the light-weight viral left-overs stay suspended in the liquid portion called the supernatant. In the subsequent step, the pellet and supernatant from each tube were separated and tested for the presence of radioactivity. Radioactive sufur was found in the supernatant, indicating that the viral protein did not go into the bacteria. Radioactive phosphorus was found in the bacterial pellet, indicating that viral DNA did go into the bacteria.

Based on these results, Hershey and Chase concluded that DNA must be the genetic code material, not protein as many poeple believed. When their experiment was published and people finally acknowledged that DNA was the genetic material, there was a lot of competition to be the first to discover its chemical structure.

Discovery of the Structure of DNA:

What was known is that DNA contains a nitrogenous base. There are two kinds of these, which include:

Nucleoside Nucleotide Each nitrogenous base is connected to a molecule of ribose sugar (1 oxygen in DNA) to form a nucleoside like the adenosine in ATP.

Each nucleoside is joined to a PO4 (phosphate group, ) to form a nucleotide like adenosine monophosphate (which can be turned into ATP by adding phosphate groups).

Deoxy Nucleotide People also knew that nucleotides were somehow linked by dehydration synthesis to form DNA, but the exact structure/arrangement was unknown.

In the early 1950s, Rosalind Franklin, an Englishwoman, was doing research which involved bouncing x-rays off crystals of various substances (a process which is called x-ray crystallography or x-ray crystal diffraction), including DNA, then exposing photographic film to the x-rays. She was studying the scatter patterns made by the x-rays bouncing off the crystals of various substances (Unfortunately, she died of cancer soon afterwards, or she might have been more famous). Other people like Linus Pauling were also attempting to figure out the structure of DNA.

Structure of DNA James Watson, a young American scientist was in England working with Francis Crick, another young researcher. Someone showed them Franklins photographs of DNA x-ray crystallography, and from her pictures, they were able to determine that the structure of DNA was organized into a double spiral or double helix. Based on Franklins data, in 1953, Watson and Crick published a paper in which they proposed and described an hypothetical structure for DNA. Subsequent research by many other people has since upheld their hypothesis, and based on subsequent examination of Franklins lab notes and calculations, she was probably within a couple days of coming to the same conclusion when their paper was published. For their discovery, Watson and Crick received the Nobel prize in 1962. In the intervening time, Rosalind Franklin had died in 1958 of ovarian cancer, probably due in large part to her work with x-rays. Since the Nobel prize is not awarded posthumously, people have often wondered if the Nobel committee would have included Franklin if she had still been alive.

Double Helix DNA Replication DNA is a double helix. The outer edges are formed of alternating ribose sugar molecules and phosphate groups. The two strands go in opposite directions (1 up and 1 down). The nitrogenous bases are inside like rungs on a ladder. Adenine on one side pairs with thymine (uracil in RNA) on the other by hydrogen bonding, and cytosine pairs with guanine. Note that the C-G pair has three hydrogen bonds while the A-T pair has only two, which keeps them from pairing wrong. This dictates side-to-side pairing, but says nothing about the order along the molecule. Watson and Crick said this variability along the molecule can account for the variety in the genetic code. Their model also accounts for how DNA can replicate itself. They said the molecule unzips and new matching bases are added in to create two new molecules. They called this semiconservative replication because each new molecule has one old and one new strand of DNA.

DNA mRNA tRNA &rarr Protein:

Here is a list of the mRNA codons and the corresponding amino acids for which they code.

B a s e

B a s e

Transcription and Translation Practice

Here is a DNA gene for some fictitious protein. Transcribe the DNA code to RNA code, then translate the RNA code to an amino acid sequence. It is set up to only accept a 3-letter code, so use the codes sta for START and sto for STOP.

Mutations and Viruses:

Mutations can be caused by a change in the sequence of the nucleotides. Some mutations have more effect than others, depending on where in the code they are and how important that area is to the code. While mutations in some areas of some genes have little effect, sickle cell anemia is caused by a mutation in only one nucleotide. This changes the codon at that location to code for a different amino acid, and that, in turn, significantly changes the shape of the hemoglobin molecules in that persons blood.

When some viruses (especially Herpes viruses, including Chicken Pox and cold sores) infect us, they insert their DNA into our cells DNA, and stay resident in our cells for the rest of our lives. These can potentially become active again either making a person sick again (like Shingles in a person who has had Chicken Pox) or just being shed from a persons body (to infect others) without obvious symptoms of illness (like Mononucleosis). Some kinds of cancer may be caused this way. For example, there is some pretty strong evidence linking genital warts (human papillomavirus, HPV) and cervical cancer.

The AIDS virus does things backwards. This virus contains RNA rather than DNA, yet when it gets into someones cells, it can do reverse transcription and code from its RNA to make DNA which, then, can code to make more virus.

Genetic Engineering Is It Good or Bad?

We now have the knowledge and ability to transfer genes from one organism to another, which seems to have some benefits associated with it, but may also have many yet-to-be-discovered problems associated with it. Because this is all so new, not enough time has elapsed to allow scientists to study/look for any possible long-term effects of genetically-modified organisms (GMOs).

For more information on genetically-modified foods, see Dr.Fankhausers Web page on that topic.

References:

Berkow, Robert, ed. 1999. The Merck Manual. 17th ed. Merck, Sharp & Dohme, Rahway, NJ.

Borror, Donald J. 1960. Dictionary of Root Words and Combining Forms. Mayfield Publ. Co.

Campbell, Neil A., Lawrence G. Mitchell, Jane B. Reece. 1999. Biology, 5th Ed. Benjamin/Cummings Publ. Co., Inc. Menlo Park, CA. (plus earlier editions)

Campbell, Neil A., Lawrence G. Mitchell, Jane B. Reece. 1999. Biology: Concepts and Connections, 3rd Ed. Benjamin/Cummings Publ. Co., Inc. Menlo Park, CA. (plus earlier editions)

Marchuk, William N. 1992. A Life Science Lexicon. Wm. C. Brown Publishers, Dubuque, IA.

There are many Web pages with information relating to the Watson-Crick-Franklin-Wilkins story. Here is a small sample of the many that were found via a search:

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DNA Structure and Function