23 Apr 2012

World’s First Handmade Cloned Transgenic Sheep born in China



April 19, 2012, Shenzhen, China - Chinese scientists from BGI, the world’s largest genomics organization, together with the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (CAS), and Shihezi University, Xinjiang province, made a significant breakthrough in animal cloning. The world’s first transgenic sheep produced with a simplified technique, handmade cloning, was successfully born at 12:16pm, March 26, 2012, in Xinjiang Uygur Autonomous Region, China. The project was also supported by the Animal Science Academy of Xinjiang.

“The transgenic sheep is named ’Peng Peng’ (after the identical given names of the two cloners),  his  birth  weight was  5.74 kg.“ said excitedly Dr. Yutao Du, Director of BGI Ark Biotechnology Co., LTD. (BAB), one of BGI’s affiliates focusing on large scale production of transgenic and cloned animals. “Peng Peng is developing normally and appears healthy” she added.

The project has been launched more than two years ago. Apart from the general inefficiency of cloning (only a small fraction of the reconstructed embryos develop to healthy offspring) cloners had to overcome additional difficulties including the special climate and compromised laboratory environment with very basic instruments. Accordingly, an innovative simplified technique called Handmade Cloning (HMC) was used, with less demand for sophisticated equipment, simplified procedures, lower costs and higher production efficiency. In 2009, donor cells were collected from a Chinese Merino sheep, and by genetic manipulation a transgenic cell line was established. After numerous attempts, the HMC system for sheep cloning was successfully established in October 2011. The transfer of the produced embryos has eventually led to the present achievement.

The genetic modification may result in improved meat quality by increasing the unsaturated fatty acid content. According to the researchers, the gene associated withω-3 poly unsaturated fatty acid (ω-3PUFA) was successfully transferred into Peng Peng. Ω-3PUFAs serve as essential fatty acids for humans reducing the risk of coronary heart disease and supporting the normal development of the brain, eye and neurons. “The birth of Peng Peng means that people could absorb ω-3PUFAs by drinking milk or eating meat in the future.” said Dr. Du, “The most difficult task has been accomplished, the transgenic sheep production platform is established, we are ready for the industrial-scale development.”

Since HMC was introduced in 2001, offspring of several important species including cattle, pig, goat and water buffalo have been produced by using this technique. The procedure may contribute to efforts to save endangered species and to produce medicines for human diseases through transgenic animals.

Last year, BGI has made great achievements on cloned transgenic mini-pigs and micro-pigs. Last August, a heroic pig, named Zhu Jiangqiang (Strong-Willed Pig), who had survived more than a month buried under rubble after the 2008 earthquake in China’s Sichuan province was also cloned, producing 6 piglets identical with the famous animal. “With each new species cloned, we learn more about the possible contribution of HMC to improve the health of animals and humans.” said Dr. Du. “I expect more breakthroughs on transgenic and cloned animal research in the foreseeable future.”

About BGI Ark Biotechnology Co., LTD

BGI Ark Biotechnology Co., LTD. Shenzhen (BAB), affiliated to BGI, is a high-tech enterprise, mainly focusing on mass production of transgenic and cloned animals.

Based on a core technology named Handmade Cloning (HMC), BAB has established a reliable and efficient standard production system, including vector construction, screening of genetically modified cell lines, reconstruction of cloned embryos, embryo transfer, among others.

Compared with traditional cloning, the benefits of handmade cloning are great. Low equipment costs, a simple and rapid procedure and a higher in vitro efficiency are valuable for large scale research in medical and agricultural sciences.

For more information about BAB, please visit www.Bab-genomics.Com.

22 Apr 2012

Appreciating the Art of Assay Development



A good assay, they say, is the stuff of good science. Whether it’s a whole new type of test, a twist or a tweak of an old one, or a way of combining things that hasn’t been worked out before, assay development remains an integral—if sometimes behind-the-scenes and underappreciated—part of the discovery process.

Just ask participants of the Assay Development and Screening track of the recent “SLAS 2012” conference. Researchers there discussed the challenges of solubilizing fatty acids while avoiding toxicity, and ways to optimize conditions for high-throughput screens of libraries of molecular inhibitions to generate more reliable hit lists.

Some told of ways to circumvent or directly challenge the idea that some targets may be “undruggable”, while another spoke of uncovering previously unseen mechanisms of action by eliminating an inhibitor built into the standard assay.

Lawrence Wiater, Ph.D., is working on cell-based assays to systematically investigate and characterize metabolism of fatty acids in mammalian cells. Biolog, for which he is a senior scientist and group leader, currently offers a series of 96-well microplates (Phenotype MicroArrays™) that look at metabolic effects of carbon and nitrogen substrates, ions, hormones, metabolic effectors, and anticancer agents. The fatty acid metabolism assays, which are currently in beta testing, will be an extension of that platform.

The assays can help researchers understand what pathways cells use to metabolize substrates that are in the wells, to look at the effects substrates have on cell growth, or to see if they can increase the productivity of a metabolic product in bioprocessing.

“You can just add your cells to hundreds of wells and then you can kinetically monitor each well for increased or decreased productivity of your favorite molecule,” Dr. Wiater pointed out. “You typically don’t know what may affect your pathway of interest. These microplates allow you to screen hundreds of nutritional factors that could modulate that productivity.”

Disease research, too, can benefit from the company’s Phenotype MicroArrays. “Energy metabolism is linked to obesity, diabetes, nutrition, aging, mitochondrial diseases, drug toxicities—especially those that target mitochondria—and then cancer and cachexia,” he said. “Our fatty acid microplates offer additional pathways you can probe to look for relevance in any of these health problems.”

Biolog’s OmniLog™ instrument incubates the microplates at 37°C while it reads and records the linear reduction of a tetrazolium dye to a colored formazan, thereby measuring the rate of metabolism in each well. Currently techniques such as mass spectrometry and liquid chromatography can generate a snapshot of metabolic pathways pools, but Dr. Wiater “doesn’t know of any other technology platform that can measure metabolic rates of fatty acids and other cell energy sources.”

Inhibit the Inhibitor

Reactivation of telomerase allows cells to become immortal, and as such is seen as an attractive anticancer target. Yet the molecular architecture of the catalytic reverse transcriptase (hTERT) of telomerase makes it essentially undruggable. Despite 15 years of trying—and a lot of money, time, and effort—no small molecule-based inhibitors of hTERT have made it to the clinic.

Cancer Research Technology (CRT) medicinal chemist Jon Roffey, Ph.D., uses a more indirect approach to find inhibitors of telomerase in his cell-based assays. He and his collaborators set out to “look for a network of druggable pathways for therapeutic exploitation of a nondruggable target,” he explained.

Using the hTERT promoter cloned by principle investigator W. Nicol Keith, Ph.D., of the University of Glasgow as the basis of a standard luciferase reporter assay, they tested the effects of 79 well-characterized kinase inhibitors. “If you can inhibit anything in that pathway, and you can inhibit promoter activity, you can see a decrease in luciferase activity,” said Dr. Roffey.

Six compounds were found that did just that, three of which were known to inhibit the activity of the enzyme glycogen synthase kinase 3 (GSK3).

But the problem with cell-based assays and reporter-gene assays is that there are multiple pathways that can lead down to the promoter, and so specificity is key. They weeded out compounds that had nonspecific effects on luciferase such as general transcription factor inhibitors, and they utilized viability assays within the cascades because it should take multiple cell cycles before shutting down telomerase would kill the cells.

Ultimately they introduced their inhibitors to the endogenous system. Using both siRNA and small molecules in a panel of cancer cell lines, the researchers were able to show that inhibiting GSK3 led to a reduction in telomerase message, a reduction in telomerase catalytic activity, and ultimately (over the course of many days) a shortening of the telomeres themselves.

The GSK3 work, Dr. Roffey explained, was not the end in itself so much as a proof of principle. It was “basically saying that the promoter assays can be used to find compounds that can modulate the pathways that modulate telomerase expression.”

Conformity

Some targets are considered “undruggable” because what’s known about their structure says that they lack traditional binding pockets for small molecules or the native ligand binds too tightly to be out-competed. X-ray crystallography, the preferred way of discerning the structure of a protein, freezes a protein into one particular conformation.

But proteins are plastic, points out Joshua Salafsky, Ph.D., CSO of Biodesy: “You’re not able to see all the conformations it’s adopting under physiological conditions, and therefore, just using crystallography, you’re unlikely to find drugs that perturb the conformation in specific ways.

“There are likely transient pockets that open up that aren’t visible in the crystal structure that you would like to develop a molecule to bind to and stabilize a particular conformation of the protein, to render it inactive, for example. Or you’d like to develop an allosteric drug, again that binds to a pocket that may or may not be visible in the crystal structure.”

While a post-doc at Columbia University, Dr. Salafsky developed a novel way to detect biomolecules, based on a technique used in physics and physical chemistry research called second harmonic generation (SHG), by labeling them with SHG-active dyes.

Subsequently, at Biodesy, the company he founded, he developed this advance into a tool to monitor a protein as its conformation changes in real time. Upon excitation, immobilized biomolecules labeled with SHG-active dyes will re-radiate two photons of red light as a single photon of blue light (the “second harmonic”).

The key, he said, is that the amount of blue light produced is very sensitive to the orientation of the dye, and so “we can detect a very small shift in the average orientation of the probe due to protein conformational change.”

By labeling a protein at a specific amine or cysteine, different parts of the protein can be monitored.

Biodesy recently used this technique to identify activators and inhibitors of Ras activity. “We not only were able to show that these compounds in fact did change the conformation of Ras directly, but that the label site also told you whether conformation changed at that particular site,” Dr. Salafsky said.

"It was really exciting that the two active compounds in our hands that changed conformation of Ras were also the two inhibitors that other people had found in cell-based assays, and that the third compound that had no effect in the cell-based assays had no effect on the conformation, in our case, either when Ras was labeled at the cysteine or at the amines.”
………………….

6 Apr 2012

Angiogenesis: Key player identified




Scientists with the University of North Carolina at Chapel Hill School of Medicine get discovered any mobile necessary protein that will takes on the key function in the formation of brand-new arteries and. The actual molecule could be the proteins Shc (evident SHIK), in addition to brand new blood vessels yacht creation, as well as angiogenesis, is usually severely damaged devoid of it.


The analysis, which often came out on the net November 16, 2011 from the journal Blood, was directed through associate professor of cell in addition to molecular physiology at UNC, Ellie Tzima, PhD, that's furthermore a member from the university's Lineberger Comprehensive Cancer Center and the McAllister Heart Institute.

"Angiogenesis is the enhancement associated with brand new blood vessels via active arteries and it's really an activity which is essential in the course of embryonic development in addition to in the advancement regarding disorders such as most cancers, " Tzima claimed. "So being familiar with the particular molecular systems associated with just how arteries and style is important through the essential science viewpoint and with regard to realizing in addition to dealing with condition. "

Vascular networks type along with increase by means of growing, as carry out timber when developing limbs. Accomplishing this enables fresh oxygen in addition to vitamins and minerals to get sent to tissue, whether in a developing embryo or a cancerous cancer. Blood vessel creation can be sparked by a number of element signals that zoom combined intricate paths. Some are cues that come coming from expansion variables, other folks in the muscle matrix how the cells take a seat on. This extracellular matrix (ECM) assists the actual cell in a number of techniques, like helping the particular cell's structure, assisting to manage cell-to-cell connection.

The proteins Shc, could manage a number of essential molecular signaling pathways, however its position inside angiogenesis offers continued to be not known until now, Tzima says.

"We hypothesized in which Shc will be the main person of which allows signals through every one of the stimuli which have been recently been shown to be very important to controlling blood vessel sourcing and also might course of action these and also manage the cell's reaction, " Tzima explained. "And that's what we found - that will Shc coordinates impulses, those people via expansion variables along with in the extracellular matrix. "

Tzima suggests that we imagine the particular cell as being a complex highway community together with electronic toll plazas through which cars having a transponder can easily wizard on motorway data transfer speeds without reducing. The system functions for the reason that transponders individualized sign are usually relayed to your computer program that will calculate the actual toll as well as charges your car's bank account in a flash. "Shc would be the toll plaza, this checkpoint where impulses essential to blood vessel enhancement must move and get coordinated intended for proper angiogenesis to happen. "

From the examine, Tzima as well as the woman team observed that Shc is necessary with regard to angiogenesis in zebrafish, mouse in addition to human endothelial cell culture models of blood vessel formation.

"The animal scientific studies offered us this broad viewpoint which Shc might be important to this technique,” explained graduate student scholar along with research first-author Daniel T. Fairly sweet. "Zebrafish in addition to mice have got formerly recently been helpful to discover blood vessel creation in vivo. All of us located in which without having Shc, blood vessel formation can be disadvantaged. "

"Then for a more detailed glimpse we utilised a new cell culture model to ascertain which endothelial cell procedures require Shc intended for angiogenesis. Many of us observed it mediates indicators via development issue receptors as well as extracellular matrix receptors, “Sweet mentioned. "Shc is vital for your crosstalk involving these kinds of techniques, meaning that they need to "talk" to each other so as to effectively form any tube in order to sprout and also migrate. That is the interesting issue with this paper. "

Tzima notes of which elegant genetic models of mice are actually accustomed to comprehend essential cellular techniques, which include angiogenesis. "But if you want to consider designing therapeutics the idea turns into additional crucial to recognize the molecular mechanism. And this had been the effectiveness of case study. We all gone completely right down to molecular friendships of which authorized all of us determine this specific completely new angiogenesis pathway. ".

5 Apr 2012

DNA Structure and Function




After you have finished reading this chapter, you should be able to:

Describe the basic structure of a chromosome, the DNA molecule, and the nucleotide subunits.
List the four nitrogenous bases and explain how they are paired.
Discuss the process of DNA replication and explain how errors in replication may cause mutations.
There is no substance as important as DNA.
James Watson, Recombinant DNA: A Short Course











LABORATORY INVESTIGATION : How Do Molecules of DNA Replicate?




see original article in PDF :DNA Structure and Function

LABORATORY INVESTIGATION : How Do Molecules of DNA Replicate?



LABORATORY INVESTIGATION
How Do Molecules of DNA Replicate?

INTRODUCTION

In 1953, Francis Crick and James Watson discovered the structure of the DNA molecule. This discovery enabled other researchers to begin to determine how molecules of DNA function. Like many other polymers, a strand of DNA is made of many individual connected subunits. A molecule of DNA consists of two parallel strands. The subunits on one strand are connected to the subunits on the other strand. It is the connections between the two strands, which can be broken and reformed, that enable DNA to make a copy of, or replicate, itself. In this laboratory investigation, you will use paper “models” of DNA subunits and portions of DNA strands to learn how this remarkable chemical is constructed and can be copied.

MATERIALS

Diagrams for steps 1–4 (from Teacher’s Manual), scissors, blank paper, tape

PROCEDURE

Step 1. Cut out the six nucleotides in the handout. Assemble them into a double strand of DNA that consists of three pairs of nucleotides that are joined together. (Hint: The phosphates attached to the sugars point up on one strand and down on the other strand. Biochemists say the two strands are “antiparallel.”) Tape the pieces into place on a sheet of paper.

Step 2. Cut out the four nucleotides from the second handout. Match them up correctly according to rules for nitrogenous-base pairing. Remember that the hydrogen bonds (dotted lines) coming from one base must match up with the hydrogen bonds in its partner. Tape the pieces into place on a sheet of paper.

Step 3. Refer to the diagram for step 3. Use the rules that govern the pairing of bases. Write the complementary base on the unlettered strand that will bond with the base shown on the lettered strand.

Step 4. Refer to the diagram for step 4. Show the replication of the 14- base-pair DNA molecule. Write in the nitrogenous base pairs after the strands have separated. Then show all the base pairs for molecules A and B. Compare these two molecules to the original.


INTERPRETIVE QUESTIONS

1. From the results in step 2, determine the two reasons why each base can pair with only one of the three types of nitrogenous bases.

2. From the results of all four steps, write a paragraph that describes how DNA is a well-organized molecule. Explain why this organization makes it possible for DNA to be the genetic material for all organisms.


CORRECTING THE ERRORS



“Do not lie on the beach without using a sunscreen lotion with at least SPF 30.” This is common advice given by doctors. Sun Protection Factor (SPF) 30 gives a person 30 times more protection from the sun than using no lotion at all. (See Figure -11.) You may wonder why we even need to be protected from the sun. Doesn’t the light of the sun provide energy for life on Earth? Although the sun’s energy is vitally important for life on Earth, sunlight also contains ultraviolet (UV) radiation. When the highenergy waves of ultraviolet light strike cells in a person’s skin, the DNA in those cells is damaged. Mutations at specific places in the DNA can occur

This damage occurs all the time. After all, the sun is shining on us much of the time, not just when we are at the beach, but also when we walk down the street or attend a ball game. In addition, other factors, including a variety of chemicals, tobacco smoke, and X rays, can cause mutations in DNA. All of these substances, including sunlight, are referred to as mutagens.

Finally, as we have mentioned, mutations occur naturally or spontaneously in the cells of our bodies all the time. What keeps our bodies operating normally most of the time is our own built-in repair system. This system consists of a series of repair enzymes that detect damaged pieces of DNA. The damaged pieces are removed, and the DNA is repaired. The problem is that sometimes, if the exposure to the mutagen is too great, too much damage occurs. The repair enzymes are unable to fix the damage. Mutations go uncorrected. Mutations frequently produce cancers, although this disease may occur many years after exposure to the mutagen. That is the reason for using the SPF 30 lotion. Ultraviolet radiation from the sun today greatly increases the risk of skin cancer later in life. One of the three types of skin cancer, malignant melanoma, has the ability to metastasize or spread throughout the body. It can kill. A blistering sunburn early in life increases the risk of cancer years later. It is necessary to help the body protect itself by minimizing one’s exposure to mutagens.


ERRORS IN DNA REPLICATION



In life, nothing is always perfect. That is true about DNA replication, too. The enzymes responsible for directing the correct pairing of nucleotides during DNA replication occasionally make mistakes. A nitrogenous base may be left out. Or the wrong base may be matched up. Sometimes an extra one is added. These mistakes produce errors in the linear sequence in one strand of the DNA molecule. Such an error is called a mutation.

From what we know about the replication process, once an error occurs in a DNA strand, it may be copied again and again. The mutation in the genetic material in one cell can easily be passed on to future cells. Are these mutations good or bad? It seems a strange question to ask, because we assume that mistakes are always bad. However, what is obvious is not always true. A mutation is simply a change. Many changes in the genetic material are harmful. In fact, many of these changes make it impossible for the future cells, or even the entire organism, to continue living. Other mutations cause the organism to change in an unnoticeable fashion. Rather than harming the organism, the mutation seems to produce no effect. Sometimes the mutation gives the organism a sudden new advantage that other similar organisms lack.

Let’s consider a simple example. Imagine that all grasshoppers in a green field were brown in color. Birds could easily see the grasshoppers and eat them. Then a mutation occurred in the DNA of one grasshopper. When that grasshopper reproduced—passing on its genetic mutation— the offspring with the mutation were green, not brown. Is this a good mutation or a bad one? Being a green grasshopper in a green field is good if it makes it harder for birds to see and eat you. This color change (mutation) to green would provide a survival advantage over the more easily seen brown grasshoppers. Natural selection would make it more likely that the green grasshoppers would survive. The species would evolve in terms of body color.

Not only can mutations in DNA be good, but they are actually an important source for the genetic variations necessary for natural selection to occur. Much of the evolution of life on Earth has depended on the chance occurrence of these mutations.


DNA REPLICATION: PASSING IT ON



To qualify as genetic material, DNA has to be able to replicate, or make a copy of, itself. This process of DNA replication occurs during the middle

of the cell cycle. What we already know about its structure is enough to explain how DNA replicates. (See Figure -9.)

To make a copy, you need an original, sometimes called a template. Because DNA is a double helix, it has templates built into it. To begin the process, the double helix unwinds. As with all metabolic activities, enzymes are needed for this process. Once the double-stranded molecule is untwisted, it begins to unzip, just like a zipper. Recall that the nitrogen base pairs A-T and G-C are connected by weak hydrogen bonds. However, at the correct moment, through the activity of an enzyme, these bonds begin to break apart. As the hydrogen bonds break, each strand of the DNA molecule becomes separate. Many free nucleotides float around in the cell. Specific enzymes match up these free nucleotides with the existing nucleotides in each DNA strand. Wherever a T is located on a strand, an A pairs to it; wherever a C is located, a G joins up, and so on. One by one, new nucleotides are joined together to make a new strand opposite each old strand. What determines the linear sequence of nucleotides in the new strands? The sequence of bases in the old strands. When replication is complete, two double-stranded DNA molecules are formed. Each molecule is made up of one old strand joined to a newly synthesized strand. How do the two new DNA molecules compare to the original one? They are identical. DNA replication has occurred. (See Figure -10.)




CHROMOSOMES: PACKAGING THE DNA



Chromosomes were observed with microscopes long before anyone knew what they were made of. Now we know that chromosomes in eukaryotes


The DNA match was made possible because Arizona now has a database that contains a DNA profile of every prison inmate. In fact, every state in America now has such a database; and a national system, the National DNA Index System (NDIS), was started in 1998. By 2002, the one-millionth DNA profile had been entered into the computerized system. DNA evidence collected from any crime scene can now be quickly compared to that of any one of the million convicted offenders in the NDIS database. The system is quickly growing and the technology of DNA testing is rapidly improving. For example, a portable DNA testing kit is under development in Britain. It will be smaller than a suitcase and will be linked to the national DNA database of that country. It is expected that the crime scene evidence will be put in a solution and then placed inside the mobile unit. Silicon chip technology in the testing kit will then extract a DNA profile that will be sent to the national database via a laptop computer. The results may be returned in under an hour to the detective’s palm-held computer. Saliva on discarded cigarette butts at crime scenes has already been used successfully to provide DNA profiles of suspects.
It is hoped that someday, thanks to this kind of technology, there will be no more wrongful convictions such as that of Mr. Krone, and more positive identifications of those who do deserve the jail time.


are made of proteins and DNA. Chromosomes are packages of DNA that seem to be held together by proteins. Why do organisms need packages of DNA?

Consider that DNA molecules are very, very long. A typical cell in the human body is much smaller than the period at the end of this sentence, and yet that single cell contains more than 2 meters of DNA. In addition, for DNA to do its job correctly, it cannot get tangled like a long piece of string thrown carelessly into a drawer. Chromosomes help maintain the DNA in the proper shape, untangled and ready for use. In a chromosome, the long double-helix DNA molecules get wound around protein molecules to form bundles. These bundles get looped together, and the loops, in turn, get coiled and folded together. This all works well to squeeze DNA into a very tight space and yet keep it well organized in order to do its job.


MAPPING THE HUMAN GENOME



At one time, determining the sequence of nucleotides in a particular type of DNA was difficult and time-consuming. In the 1960s, it took seven years to determine the sequence of a DNA molecule with only 77 nucleotides. Now, like many other tasks, the analysis of DNA is automated. Laboratory equipment analyzes DNA quickly, and computers tabulate the results. Because of these technological advances, in the late 1980s molecular biologists began to plan for what they considered the most important biology investigation of all time: determining the entire nucleotide sequence of human DNA. In 1992, a worldwide effort—the Human Genome Project—began to analyze the three billion base pairs of human DNA. If printed on paper, the linear sequence of DNA contained in each of our cells would require 2000 books the size of this one. Molecular biologists all over the world are working together on this project, and they expect to finish before the year 2005.

In 1998, a well-known geneticist, along with a highly respected research company that makes machines to analyze DNA, announced that they planned to map the human genome faster and for less money than the government-sponsored Human Genome Project. They claimed that for only $200 million they would be done in just three years. The public may have been concerned that one private company could control so

Death-Row Inmate Cleared by DNA Evidence

Every time a prisoner awaiting a death sentence is proven innocent by DNA evidence and released, it makes the news. And it should. Nothing demonstrates the power of DNA technology better. Ray Krone owes his freedom, and probably his life, to this technology. In 2002, he was released from an Arizona prison after serving 10 years. During that time, Mr. Krone, who had served in the U.S. Air Force and worked as a letter carrier with no criminal record, was tried twice for the sexual assault and stabbing murder of a bartender in 1991. Mr. Krone was in the bar where the victim worked the night of the murder. The only evidence used to convict him was the similarity between the pattern of tooth marks on the victim, where she had been bitten, and Mr. Krone’s teeth.
The first trial sentenced Mr. Krone to death, the second trial to a life sentence. Finally, after 10 years, DNA testing was done on saliva from bite marks found on the victim’s clothing. Not only did the DNA not match that of Mr. Krone, but it did match that of a person serving time in another Arizona prison for an unrelated sex crime. The odds were 1.3 quadrillion (1,300,000,000,000,000) to 1 that it was this other man’s DNA on the victim and not that of Mr. Krone or anyone else. A judge ordered the immediate release of Ray Krone when the DNA test results were announced.

much important information. However, most scientists agreed that the sooner the complete human genome was decoded, the sooner more research could be conducted to understand what it all means. By 2001, the first working draft sequence of the entire human genome was published.

Scientists agree that the Human Genome Project, described by some people as the effort to read the “book of humankind,” is just the beginning of human genetic research. Only through this effort will we be able to understand ourselves on the molecular level, the most basic level of all. Indeed, scientists aim to someday understand all life-forms on this level. In 2002, six more model organisms were chosen to have their entire genetic codes spelled out. These six are the chimpanzee, the chicken, the honeybee, the sea urchin, a yeastlike protozoan, and a family of fungi.


DNA: A LIBRARY OF INFORMATION



The words of any language are a means to store and transmit information. For example, all English words are made from combinations of the 26 letters in the alphabet. Many, many words can be made from these letters. An unabridged dictionary contains 450,000 words, all made from only 26 different letters. In some ways, the nucleotides in DNA are like the letters of the alphabet, only the DNA letters are “chemical” letters. Because there are only four letters—A, T, G, and C—in the DNA alphabet, scientists thought that DNA was too simple to contain the complex genetic information of life. But what is also significant in DNA is the sequence of the letters, not only the letters themselves. Using these four letters in long sequences, nature can create an almost unlimited variety of genetic messages. In fact, by creating messages only ten nucleotides long, it is possible to make more than one million different sequences or messages with the four nucleotides.

When you realize that human DNA consists of not ten but three billion pairs of nitrogenous bases, you can begin to imagine how much information can be stored in the DNA of our cells! All of the information for constructing our bodies, determining all of our characteristics or traits, and keeping our bodies running is stored in the linear sequences of nucleotides in our DNA. The same is true for every bacterial cell, insect, fish, bird, tree, and all other organisms on Earth. Once scientists realized the importance of the linear sequence of DNA nucleotides, they were anxious to determine the sequence of nucleotides in a particular DNA molecule. In Chapter 2, you learned about one important reason for doing this. The evolutionary relationship of two organisms can be learned by comparing their DNA. The more similar their nucleotide sequences, the more recently the two organisms evolved from a common ancestor. (See Figure -8.)

To make use of the genetic information stored in DNA, organisms must change the information into proteins. Proteins are made up of amino acids that are linked to each other. So, a protein is another linear sequence of subunits. In the next chapter, you will learn how the information stored in DNA gets expressed in the form of proteins.

Check Your Understanding
Why is the sequence of nucleotides in each strand of a DNA molecule so important? (Give more than one reason.)

THE WORLD LEARNS OF THE DOUBLE HELIX



Professionals are always seeking fascinating projects to work on. In 1953, James Watson, a young investigator by the united states, went to Cambridge University in England. He joined Francis Crick, a physicist, mainly because both equally ones have been considering studying a lot more with regards to DNA. Several others had been considering mastering DNA then. Numerous researchers assumed which wanting to decipher your framework of DNA would likely grow to be very dull operate. And in addition they imagined it may not possibly be in any way crystal clear how DNA capabilities because the genetic material.

To acquire more information about the construction associated with DNA, Watson and also Crick would not work just how almost all scientists do. Many people did not perform long combination of experiments within a laboratory work. Rather, these people utilized data by now acknowledged regarding DNA molecules and also built types of elements along with houses to install the data. (See Figure -4)

It absolutely was regarded which DNA has been derived from scaled-down nucleotide subunits. Every single nucleotide is made up of five-carbon sugar termed deoxyribose, the phosphate, as well as a nitrogenous starting. A chemist at Columbia University, Erwin Chargaff, got found that the actual 4 kinds of nitrogenous basics within DNA actually shaped a couple of pairs. Your degrees of adenine (A) in addition to thymine (T) were being always exactly the same (A = T). The variety of guanine (G) and cytosine (C) ended up constantly the same (G = C). Another vital piece of information which Watson along with Crick had was via images obtained when x rays were being opportunity via uric acid involving DNA. Named X-ray diffraction patterns, most of these pictures have been obtained by simply Rosalind Franklin along with Maurice Wilkins. It had been decided off their images that the DNA molecule experienced any control, or even helical, pattern-a design of which appears to be a new get out of hand staircase or your post of your wooden attach. (Observe Figure -5.)


Using this type of info, primarily based mainly about the operate connected with additional professionals, Watson along with Crick utilized tin and wire to make a large design. The type of DNA, in the shape of some sort of increase helix, as opposed to currently being uninteresting, was regarding the the majority of enjoyable finding within the history associated with biology.

The easiest way to be aware of the particular dual helix structure regarding DNA is usually to snapshoot a new ladder that's been twisted. The two attributes with the hierarchy are usually parallel together. The actual steps on the ladder hyperlink both the facets to each other.


On this model, the particular factors from the ladder include the sugar-phosphate spine in the DNA molecule. Changing deoxyribose sugar and phosphate substances make-up this specific anchor. Stretching out involving the 2 sides, from your sugars one aspect with a sugar within the various other, usually are sets regarding molecules that contain nitrogen. They are the nitrogenous angles. Just one sugar, one phosphate, and another nitrogenous basic make-up any nucleotide. Your nucleotides using one area of the molecule are bonded together to make one side, or strand, of the molecule. Other nucleotides are bonded together to make up the other side of the DNA molecule. (See Figure -6.)

Finally, how are the two sides of the molecule joined? The answer to this involves the nitrogenous base pairs. TheWatson-Crick model showed that the only possible way all the parts could fit was for each large adenine base to be matched opposite a smaller thymine base. Similarly, a larger guanine had to be opposite a smaller cytosine. These nitrogenous bases were joined by fairly weak hydrogen bonds between them. It is now possible to realize the importance of Chargaff’s discovery, A = T and G = C.

So a molecule of DNA consists of two strands, opposite each other, connected by matching nitrogenous base pairs. If we look at one strand, we can describe it in terms of the order or sequence of nucleotides. A DNA molecule may be very long. Because the nucleotides are in a long line, the order of the nucleotides is called a linear sequence. Imagine walking along a single strand of DNA. The bases in the nucleotides may occur in any order. The linear sequence on a short molecule of DNA might be A-T-T-G-A-C-C-G. Now imagine walking along the opposite strand starting at the same place. Opposite the A in the first strand is a T. Because we know the sequence of nucleotides in the first strand, we automatically know the sequence of nucleotides in the other strand. In this example, beginning with the T, it must be T-A-A-C-T-G-G-C. This is the key to how the DNA copies itself. The copying of DNA is replication and it depends on the matching nitrogenous base pairs in the nucleotides of each strand. (See Figure -7.)


What is so important about the order of the nucleotides in a strand of DNA? Everything! The sequence of nucleotides is the information that the strand of DNA contains.