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Francis Collins

Francis Collins

Francis S. Collins, M.D., Ph.D., a physician-geneticist noted for his landmark discoveries of disease genes, and his visionary leadership of the Human Genome Project (HGP), is director of the National Human Genome Research Institute (NHGRI). As head of NHGRI, Collins has overseen the HGP, the multidisciplinary, multi-institutional, international effort to map and sequence all of the human DNA and then determine aspects of its function. Many consider this project to be the most significant scientific undertaking of our time. The ultimate goal is to improve human health. With Collins at the helm, the HGP has attained historic milestones, while consistently running ahead of schedule and under budget. A working draft of the human genome sequence was announced in June 2000, and an initial analysis was published in February 2001. HGP scientists are continuing to work toward finishing the sequence of all three billion base pairs by 2003, coinciding with the 50th anniversary of Watson and Crick's seminal publication of the structure of DNA. Perhaps more importantly, Collins' unswerving commitment to free, rapid access to genomic information made all data immediately available to the worldwide scientific community without restrictions on access or use. With these immense data sets of DNA sequence and variation in hand, researchers around the globe are now equipped to accelerate the process of understanding the connection between genes and disease, which Collins envisions as a new era of individualized, prevention-oriented medicine.

Beginnings

Raised on a small farm in Virginia's Shenandoah Valley, Collins was home-schooled until the sixth grade. Throughout most of his high school and college years, the aspiring chemist had little interest in what he then considered the "messy" field of biology. What he refers to as his "formative education" was received at the University of Virginia, where he earned a B.S. in Chemistry in 1970. He went on to attain a Ph.D. in physical chemistry at Yale University in 1974. While at Yale, however, a course in biochemistry sparked his interest in the molecules that hold the blueprint for life: DNA and RNA. Collins recognized that a revolution was on the horizon in molecular biology and genetics. After consulting with his old mentor from the University of Virginia, Carl Trindle, he changed fields and enrolled in medical school at the University of North Carolina, earning there an M.D. in 1977. From 1978 to 1981, Collins served a residency and chief residency in internal medicine at North Carolina Memorial Hospital in Chapel Hill. He then returned to Yale, where he was named a Fellow in Human Genetics at the medical school from 1981 to1984. During that time, he developed innovative methods of crossing large stretches of DNA to identify disease genes. After joining the University of Michigan in 1984 in a position that would eventually lead to a Professorship of Internal Medicine and Human Genetics, Collins heightened his reputation as a relentless gene hunter. That gene-hunting approach, which he named "positional cloning," has developed into a powerful component of modern molecular genetics. In contrast to previous methods for finding genes, positional cloning enabled scientists to identify disease genes without knowing in advance what the functional abnormality underlying the disease might be. Collins' team, together with collaborators, applied the new approach in 1989 in their successful quest for the long-sought gene responsible for cystic fibrosis. Other major discoveries soon followed, including isolation of the genes for Huntington's disease, neurofibromatosis, multiple endocrine neoplasia type 1, and the M4 type of adult acute leukemia.

Leadership at NHGRI

Tapped to take on the leadership of the HGP, Collins accepted an invitation in 1993 to become director of the National Center for Human Genome Research, which became NHGRI in 1997. As director, he oversees the International Human Genome Sequencing Consortium and many other aspects of what he has called "an adventure that beats going to the moon or splitting the atom." In 1994, Collins founded NHGRI's Division of Intramural Research (DIR), an intramural program of genome research that has developed into one of the nation's premier research centers in human genetics. With new tools arising from the human genome project, Collins is optimistic about the chances of uncovering hereditary contributors to common diseases, such as heart disease, cancer and mental illness. In the overall research agenda of NHGRI, this interest is reflected in the highly ambitious effort to construct a haplotype map of the human genome. The "hap map" will serve as a catalog of genetic variations - called single nucleotide polymorphisms (SNPs) - and will help with discovering how these variations correlate with disease risk. Collins's work in his highly active lab demonstrates that research emphasis, which is devoted to finding the genes that contribute to adult-onset, Type II diabetes. In addition to his long list of contributions to basic genetic research and scientific leadership, Collins is known for his close attention to ethical and legal issues in genetics. He has been a strong advocate for protecting the privacy of genetic information and has served as a national leader in efforts to prohibit gene-based insurance discrimination. Building on his own experiences as a physician volunteer in a rural missionary hospital in Nigeria, Collins is also very interested in opening avenues for genome research to benefit the health of people living in developing nations. Collins' accomplishments have been recognized by numerous awards and honors, including election to the Institute of Medicine and the National Academy of Sciences.

Personal

He was the youngest child having three older brothers. He is divorced but currently, as of February 2005, engaged to be married. He has two daughters from the first marriage. He was raised only nominally Christian and therefore by graduate school he described himself as an "obnoxious atheist." However dealing with dying patients changed that and he is now a generally strong Christian who delivers lectures at churches concerning C. S. Lewis.

External links

- [http://www.genome.gov/10001018 Information from genome.gov]
- [http://www.achievement.org/autodoc/page/col1int-1 Francis S. Collins interview]
- [http://www.virginia.edu/majorevents/speeches/01speech.html Commencement Address, University of Virginia, May 20, 2001] Collins Category:Geneticists Collins, Francis Collins, Francis

Human Genome Project

The Human Genome Project (HGP) endeavored to map the human genome down to the nucleotide (or base pair) level and to identify all the genes present in it.

History

The Project was launched in 1986 by Charles DeLisi, who was then Director of the US Department of Energy's Health and Environmental Research Programs. The goals and general strategy of the Project were outlined in a two-page memo to the Assistant Secretary in April 1986, which helped garner support from the DOE, the OMB and Congress, especially Senator Pete Domenici. A series of Scientific Advisory meetings, and complex negotiations with senior Federal officials resulted in a line item for the Project in the 1987 Presidential budget submission to the Congress. Initiation of the Project was the culmination of several years of work supported by the US Department of Energy, in particular a feasibility workshop in 1986 and a subsequent [http://www.ornl.gov/sci/techresources/Human_Genome/project/herac2.shtml detailed description of the Human Genome Initiative] in a report that led to the formal sanctioning of the initiative by the Department of Energy. This 1987 report stated boldly, "The ultimate goal of this initiative is to understand the human genome" and "Knowledge of the human genome is as necessary to the continuing progress of medicine and other health sciences as knowledge of human anatomy has been for the present state of medicine". Candidate technologies were already being considered for the proposed undertaking at least as early as 1985. The $3 billion project was formally founded in 1990 by the United States Department of Energy and the U.S. National Institutes of Health, and was expected to take 15 years. In addition to the United States, the international consortium comprised geneticists in China, France, Germany, Japan, and the United Kingdom. Due to widespread international cooperation and advances in the field of genomics (especially in sequence analysis), as well as huge advances in computing technology, a rough draft of the genome was finished in 2000 (announced jointly by US president Bill Clinton and British Prime Minister Tony Blair on June 26, 2000), two years earlier than planned. President Clinton had already awarded the Citizen's medal to DeLisi for his seminal role in the Project, in January 2000, before the completion of the Project was announced.

The Role of Celera Genomics

In 1998, an identical, privately funded quest was launched by researcher Craig Venter and his firm Celera Genomics. The $300 million Celera effort was intended to proceed at a faster pace and at a fraction of the cost of the roughly $3 billion taxpayer-funded project. Celera used a newer, riskier technique called whole genome shotgun sequencing, which had been used to sequence bacterial genomes. Celera initially announced that it would seek patent protection on "only 200-300" genes, but later amended this to seeking "intellectual property protection" on "fully characterized important structures" amounting to 100-300 targets. The firm eventually filed [http://news.bbc.co.uk/1/hi/sci/tech/487773.stm patent applications on 6,500 whole or partial genes]. Celera also promised to publish their findings in accordance with the terms of the 1996 "Bermuda Statement", by releasing new data quarterly (the HGP released its new data daily), although, unlike the publicly-funded project, they would not permit free redistribution or commercial use of the data. In March 2000, President Clinton announced that the genome sequence could not be patented, and should be made freely available to all researchers. The statement sent Celera's stock plummeting and dragged down the biotech-heavy Nasdaq. The biotech sector lost about $50 billion in market capitalization in two days. Although the working draft was announced in June 2000, it was not until February 2001 that Celera and the HGP scientists published details of their drafts. Special issues of Nature (which published the publicly-funded project's scientific paper) and Science (which published Celera's paper) described the methods used to produce the draft sequence and offered analysis of the sequence. These drafts are hoped to comprise a 'scaffold' of 90 percent of the genome, with gaps to be filled later. The competition proved to be very good for the project. The rivals agreed to pool their data, but the agreement fell apart when Celera refused to deposit its data in the unrestricted public database Genbank. Celera had incorporated the public data into their genome, but forbade the public effort to use Celera data. On 14 April 2003, a joint [http://www.genoscope.cns.fr/externe/CHODE/English/Actualites/Presse/HGP/HGP_press_release-140403.pdf press release] announced that the project had been completed by both groups, with 99 percent of the genome sequenced with 99.99 percent accuracy. Each draft sequence has been checked at least four to five times to increase 'depth of coverage' or accuracy. About 47 percent of the draft were high-quality sequences. The final version will have been checked eight to nine times giving an error rate of 1 in 10,000 bases. HGP is one of several international genome projects aimed at sequencing the DNA of a specific organism. While the human DNA sequence offers the most tangible benefits, important developments in biology and medicine are predicted as a result of the sequencing of model organisms, including mice, fruitflies, zebrafish, yeast, nematodes and many microbial organisms and parasites. In October 2004, researchers of the HGP announced a new estimate of 20,000 to 25,000 genes in the human genome. Previously 30,000 to 40,000 had been predicted, while estimates at the start of the project reached up to as high as 100,000.

Goals

The goals of the original HGP were not only to determine all 3 billion base pairs in the human genome with a minimal error rate, but also to identify all the genes in this vast amount of data. This part of the project is still ongoing although a preliminary count indicates about 30,000 genes in the human genome, which is far fewer than predicted by most scientists. Another goal of the HGP was to develop faster, more efficient methods for DNA sequencing and sequence analysis and the transfer of these technologies to industry. The sequence of the human DNA is stored in databases available to anyone on the Internet. The U.S. National Center for Biotechnology Information (and sister organizations in Europe and Japan) house the gene sequence in a database known as Genbank, along with sequences of known and hypothetical genes and proteins. Other organizations such as the University of California, Santa Cruz, and [http://www.ensembl.org ENSEMBL] present additional data and annotation and powerful tools for visualizing and searching it. Computer programs have been developed to analyse the data, because the data itself is difficult to interpret without them. The process of identifying the boundaries between genes and other features in raw DNA sequence is called genome annotation and is the domain of bioinformatics. While expert biologists make the best annotators, their work proceeds slowly, and computer programs are increasingly used to meet the high-throughput demands of genome sequencing projects. The best current technologies for annotation make use of statistical models that take advantage of parallels between DNA sequences and human language, using concepts from computer science such as formal grammars. All humans have unique gene sequences, therefore the data published by the HGP does not represent the exact sequence of each and every individual's genome. It is the combined genome of a small number of anonymous donors. The HGP genome is a scaffold for future work in identifying differences between individuals. Most of the current effort in identifying differences between individuals involves single nucleotide polymorphisms.

Benefits

Clear practical results of the project emerged even before the work was finished. For example, a number of companies, such as Myriad Genetics started offering inexpensive and easy to administer genetic tests that can show predisposition to a variety of illnesses, including breast cancer, blood clotting, cystic fibrosis, liver diseases and many others. There are also many tangible benefits for biological scientists. For example, a researcher investigating a certain form of cancer may have narrowed down his search to a particular gene. By visiting the human genome database on the world-wide web, this researcher can examine what other scientists have written about this gene, including (potentially) its three-dimensional structure, its function(s), its evolutionary relationships to other human genes, or to genes in mice or yeast or fruitflies, possible detrimental mutations, interactions with other genes, body tissues in which this gene is activated, diseases associated with this gene... the list of datatypes is long, one reason why bioinformatics is so challenging. The work on interpretation of genome data is still in its initial stages. In the future the knowledge gained by the understanding of the genome will boost the fields of medicine and biotechnology, eventually leading to cures for cancer, Alzheimer's disease and other diseases. On a more philosophical level, the analysis of similarities between DNA sequences from different organisms is opening new avenues in the study of the theory of evolution. In many cases, evolutionary questions can now be framed in terms of molecular biology; indeed, many major evolutionary milestones (the emergence of the ribosome and organelles, the development of embryos with body plans, the vertebrate immune system) can be related to the molecular level. Many questions about the similarities and differences between humans and our closest relatives (the primates, and indeed the other mammals) are expected to be illuminated by the data from this project. See also: genetics, bioinformatics

References

# . Retrieved 2005-02-03. # Retrieved 2005-02-03.
- [http://www.wired.com/news/medtech/0,1286,66822,00.html DNA Testing Goes DIY], Associated Press via Wired News, March 07, 2005.

External links

- [http://www.ornl.gov/sci/techresources/Human_Genome/publicat/hgn/hgn.shtml Human Genome News]. Published from 1989 to 2002 by the US Department of Energy, this newsletter was a major communications method for coordination of the Human Genome Project. Complete online archives are available.
- Project Gutenberg hosts e-texts for Human Genome Project, titled Human Genome Project, Chromosome Number # (# denotes 01-22, X and Y). This information is raw sequence, released in November 2002; access to entry pages with download links is available through http://www.gutenberg.org/etext/3501 for Chromosome 1 sequentially to http://www.gutenberg.org/etext/3524 for the Y Chromosome. Note that this sequence might not be considered definitive due to ongoing revisions and refinements. In addition to the chromosome files, there is a [http://www.gutenberg.org/etext/11799 supplementary information file] dated March 2004 which contains additional sequence information.
- [http://www.doegenomes.org/ The HGP information pages]
- [http://www.ensembl.org/ Ensembl project], an automated annotation system and browser for the human genome
- [http://genome.ucsc.edu UCSC genome browser]
- [http://www.nature.com/genomics/human/ Nature magazine's human genome gateway], including the HGP's paper on the draft genome sequence
- [http://www.wellcome.ac.uk/en/genome/ Wellcome charitable trust description of HGP] "Your Genes, your health, your future".
- [http://www.ericdigests.org/2003-2/genome.html Learning about the Human Genome. Part 1: Challenge to Science Educators. ERIC Digest.]
- [http://www.ericdigests.org/2003-2/genome2.html Learning about the Human Genome. Part 2: Resources for Science Educators. ERIC Digest.]
- [http://www.prospect.org/print/V11/26/goozner-m.html Patenting Life by Merrill Goozner]
- [http://www.nationalreview.com/comment/comment062700a.html Genome Breakthrough by Ronald Bailey]
- [http://clinton4.nara.gov/WH/EOP/OSTP/html/00626_4.html Prepared Statement of Craig Venter of Celera] Venter discusses Celera's progress in deciphering the human genome sequence and its relationship to healthcare and to the federally funded Human Genome Project.
- [http://www.objectivescience.com/articles/genes_holcberg.htm Clinton Tries To Take Credit For Celera's Achievement by David Holcberg]
- Category:Big Science Category:Genome projects Category:U.S._sponsored_enterprises ja:ヒトゲノム計画 th:โครงการจีโนมมนุษย์

Nhgri

The National Human Genome Research Institute (NHGRI) is a division of the National Institutes of Health, located in Bethesda, Maryland. The NHGRI was founded in 1989 as part of the National Institutes of Health to lead the Human Genome Project, whose goal was to map and sequence the entire human genome. The major portion of this was accomplished in April of 2003. NHGRI works on many types of high throughput studies to map and sequence organisms that might better aid in the understanding of how genomes work. They have funded the sequencing of many different genome projects including the mouse, rat, chicken, and dog genomes as well. The NHGRI also researches treatments for genetic disorders as well as genetic susceptibility loci for many common diseases.

External links

- [http://www.genome.gov/ NHGRI Homepage] (Genome.gov) Category:Genetics or genomics research institutions Human Genome Research Institute

DNA

:For other uses, see DNA (disambiguation). DNA (disambiguation) Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). DNA is a long polymer of nucleotides and encodes the sequence of the amino acid residues in proteins using the genetic code, a triplet code of nucleotides. In complex cells (eukaryotes), such as those from plants, animals, fungi and protists, most of the DNA is located in the cell nucleus. By contrast, in simpler cells called prokaryotes (the eubacteria and archaea), DNA is not separated from the cytoplasm by a nuclear envelope. The cellular organelles known as chloroplasts and mitochondria also carry DNA. DNA is often referred to as the molecule of heredity as it is responsible for the genetic propagation of most inherited traits. These traits can range from hair colour to disease susceptibility. During cell division, DNA is replicated and can be transmitted to offspring during reproduction. Lineage studies can be done based on the facts that the DNA in mitochondria (mitochondrial DNA) only comes from the mother, and the male "Y" chromosome only comes from the father. Every person's DNA, their genome, is inherited from both parents. The mother's mitochondrial DNA together with twenty-three chromosomes from each parent combine to form the genome of a fertilized egg. As a result, with certain exceptions such as red blood cells, most human cells contain 23 pairs of chromosomes, together with mitochondrial DNA inherited from the mother.

DNA Overview

red blood cell This section presents an introductory and therefore incomplete overview of DNA.
- Genes can be loosely viewed as the organism's "cookbook" or "blueprint";
- A strand of DNA contains genes, areas that regulate genes, and areas that either have no function, or a function we do not (yet) know (also see last bullet point in this section for the difference between DNA and RNA);
- DNA is organized as two complementary strands, head-to-toe, with bonds between them that can be "unzipped" like a zipper, separating the strands;
- DNA is a chain of chemical "building blocks", called "bases", of which there are four types: these can be abbreviated A, T, C, and G. Each base can only "pair up" with one single predetermined other base: A+T, T+A, C+G and G+C are the only possible combinations; that is, an "A" on one strand of double-stranded DNA will "mate" properly only with a "T" on the other, complementary strand;
- N.B.: U occasionally replaces T, notably in PBS1 phage DNA; you can thus substitute "U" for "T" throughout this section.
- Because each strand of DNA has a directionality, the sequence order does matter: A+T is not the same as T+A, just as C+G is not the same as G+C;
- For each given base, there is just one possible complementary base, so naming the bases on the conventionally chosen side of the strand is enough to describe the entire double-strand sequence;
- The genetic information contained in a strand of DNA is determined by the sequence of bases along its length;
- The cell begins DNA replication by forcibly unzipping the DNA double strand down the middle, and then recreates the "other half" of each new single strand by drowning each half in a "soup" made of the four bases. An enzyme makes a new strand by finding the correct "base" in the soup and pairing it with the original strand. In this way, the base on the old strand dictates which base will be on the new strand, and the cell ends up with an extra copy of its DNA.
- Mutations are simply chemical imperfections in this process: a base is accidentally skipped, inserted, or incorrectly copied, or the chain is trimmed, or added to; many basic mutations can be described as combinations of these accidental "operations". Mutations can also occur through chemical damage (through mutagens), light (UV damage), or through other more complicated gene swapping events.
- DNA (for DeoxyriboNucleic Acid) differs from RNA (for RiboNucleic Acid) by having the sugar 2-deoxyribose instead of ribose in its backbone (ribose contains one extra oxygen atom compared to deoxyribose -- in other words, DNA contains deoxygenated ribose, whereas RNA contains "plain" ribose.) This is the basic chemical distinction between RNA and DNA.

DNA in practice

DNA in crime

Forensic scientists can use DNA located in blood, semen, skin, saliva, or hair left at the scene of a crime to identify a possible suspect, a process called genetic fingerprinting or DNA profiling. In DNA profiling the relative lengths of sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared. DNA profiling was developed in 1984 by English geneticist Alec Jeffreys, and was first used in 1986 in the Enderby murders case in Leicestershire, England. Many jurisdictions require convicts of certain types of crimes to provide a sample of DNA for inclusion in a computerized database. This has helped investigators solve old cases where the perpetrator was unknown and only a DNA sample was obtained from the scene (particularly in rape cases between strangers). This method is one of the most reliable techniques for identifying a criminal, but is not always perfect, for example if no DNA can be retrieved, or if the scene is contaminated with the DNA of several possible suspects.

DNA in computation

Despite its biological origins, DNA plays an important role in computer science, both as a motivating research problem and as a method of computation in itself, called DNA computing. As a simple example, research on string searching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, was motivated by DNA research, where it is used to find specific sequences of nucleotides in a large sequence. In other applications like text editors, even simple algorithms for this problem usually suffice, but DNA sequences cause these algorithms to exhibit near-worst-case behavior due to their small number of distinct characters. Databases have also been strongly motivated by DNA research, which requires special tools for storing and manipulating DNA sequences. Databases specialized for this purpose are called genomic databases, and have a number of unique technical challenges associated with the operations of approximate matching, sequence comparison, finding repeating patterns, and homology searching. In 1994, Leonard Adleman of the University of Southern California made headlines when he discovered a way of solving the directed Hamiltonian path problem, an NP-complete problem, using tools from molecular biology, in particular DNA. The new approach, dubbed DNA computing, has practical advantages over traditional computers in power use, space use, and efficiency, due to its ability to highly parallelize the computation (see parallel computing)(there is labor worth mention involved in retrieving answers computed these computational DNA techniques.). A number of other problems, including simulation of various abstract machines, the boolean satisfiability problem, and the bounded version of the Post correspondence problem, have since been analyzed using DNA computing. Due to its compactness, DNA also has an important role in cryptography, where in particular it allows unbreakable one-time pads to be efficiently constructed and used.[http://citeseer.ist.psu.edu/gehani99dnabased.html]

Overview of molecular structure

one-time pad Although sometimes called "the molecule of heredity", pieces of DNA as people typically think of them are not single molecules. Rather, they are pairs of molecules, which entwine like vines to form a double helix (see the illustration at the right). Each vine-like molecule is a strand of DNA: a chemically linked chain of nucleotides, each of which consists of a sugar, a phosphate and one of five kinds of nucleobases ("bases"). Because DNA strands are composed of these nucleotide subunits, they are polymers. The diversity of the bases means that there are five kinds of nucleotides, which are commonly referred to by the identity of their bases. These are adenine (A), thymine (T), uracil (U), cytosine (C), and guanine (G). U is rarely found in DNA except as a result of chemical degradation of C, but in some viruses, notably PBS1 phage DNA, U completely replaces the usual T in its DNA. Similarly, RNA usually contains U in place of T, but in certain RNAs such as transfer RNA, T is always found in some positions. Thus, the only true difference between DNA and RNA is the sugar, 2-deoxyribose in DNA and ribose in RNA. In a DNA double helix, two polynucleotide strands can associate through the hydrophobic effect and pi stacking. Specificity of which strands stay associated is determined by complementary pairing. Each base forms hydrogen bonds readily to only one other -- A to T and C to G -- so that the identity of the base on one strand dictates the strength of the association; the more complementary bases exist, the stronger and longer-lasting the association. The cell's machinery is capable of melting or disassociating a DNA double helix, and using each DNA strand as a template for synthesizing a new strand which is nearly identical to the previous strand. Errors that occur in the synthesis are known as mutations. The process known as PCR (polymerase chain reaction) mimics this process in vitro in a nonliving system. Because pairing causes the nucleotide bases to face the helical axis, the sugar and phosphate groups of the nucleotides run along the outside; the two chains they form are sometimes called the "backbones" of the helix. In fact, it is chemical bonds between the phosphates and the sugars that link one nucleotide to the next in the DNA strand.

The role of the sequence

Within a gene, the sequence of nucleotides along a DNA strand defines a messenger RNA sequence which then defines a protein, that an organism is liable to manufacture or "express" at one or several points in its life using the information of the sequence. The relationship between the nucleotide sequence and the amino-acid sequence of the protein is determined by simple cellular rules of translation, known collectively as the genetic code. The genetic code is made up of three-letter 'words' (termed a codon) formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). These codons can then be translated with messenger RNA and then transfer RNA, with a codon corresponding to a particular amino acid. There are 64 possible codons (4 bases in 3 places

4^3

) that encode 20 amino acids. Most amino acids, therefore, have more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region, namely the UAA, UGA and UAG codons. In many species, only a small fraction of the total sequence of the genome appears to encode protein. For example, only about 1.5% of the human genome consists of protein-coding exons. The function of the rest is a matter of speculation. It is known that certain nucleotide sequences specify affinity for DNA binding proteins, which play a wide variety of vital roles, in particular through control of replication and transcription. These sequences are frequently called regulatory sequences, and researchers assume that so far they have identified only a tiny fraction of the total that exist. "Junk DNA" represents sequences that do not yet appear to contain genes or to have a function. The reasons for the presence of so much non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size ("C-value") among species represent a long-standing puzzle in DNA research known as the "C-value enigma". Some DNA sequences play structural roles in chromosomes. Telomers and centromeres typically contain few (if any) protein-coding genes, but are important for the function and stability of chromosomes. Some genes code for "RNA genes" (see tRNA and rRNA). Some RNA genes code for transcripts that function as regulatory RNAs (see siRNA) that influence the function of other RNA molecules. The intron-exon structure of some genes (such as immunoglobin and protocadeherin genes) is important for allowing alternative splicing of pre-mRNA which allows several different proteins to be made from the same gene. Some non-coding DNA represents pseudogenes that can be used as raw material for the creation of new genes with new functions. Some non-coding DNA provided hot-spots for duplication of short DNA regions; such sequence duplication has been the major form of genetic change in the human lineage (see evidence from the Chimpanzee Genome Project). Exons interspersed with introns allows for "exon shuffling" and the creation of modified genes that might have new adaptive functions. Large amounts of non-coding DNA is probably adaptive in that it provides chromosomal regions where recombination between homologous portions of chromosomes can take place without disrupting the function of genes. Some biologists such as Stuart Kauffman have speculated that there must be mechanisms by which the rate of evolution of a species can be increased or decreased. Non-coding DNA provides mechanisms for gene creation, modification and recombination it is probably important for control of the rate of human evolution. Sequence also determines a DNA segment's susceptibility to cleavage by restriction enzymes, the quintessential tools of genetic engineering. The position of cleavage sites throughout an individual's genome determines one kind of an individual's "DNA fingerprint".

DNA replication

Main article: DNA replication DNA replication DNA replication or DNA synthesis is the process of copying the double-stranded DNA prior to cell division. The two resulting double strands are generally almost perfectly identical, but occasionally errors in replication can result in a less than perfect copy (see mutation), and each of them consists of one original and one newly synthesized strand. This is called semiconservative replication. The process of replication consists of three steps: initiation, replication and termination.

Mechanical properties relevant to biology

Main article: Mechanical properties of DNA.

Strands association and dissociation

The hydrogen bonds between the strands of the double helix are weak enough that they can be easily separated by enzymes. Enzymes known as helicases unwind the strands to facilitate the advance of sequence-reading enzymes such as DNA polymerase. The unwinding requires that helicases chemically cleave the phosphate backbone of one of the strands so that it can swivel around the other. The strands can also be separated by gentle heating, as used in PCR, provided they have fewer than about 10,000 base pairs (10 kilobase pairs, or 10 kbp). The intertwining of the DNA strands makes long segments difficult to separate.

Circular DNA

When the ends of a piece of double-helical DNA are joined so that it forms a circle, as in plasmid DNA, the strands are topologically knotted. This means they cannot be separated by gentle heating or by any process that does not involve breaking a strand. The task of unknotting topologically linked strands of DNA falls to enzymes known as topoisomerases. Some of these enzymes unknot circular DNA by cleaving two strands so that another double:stranded segment can pass through. Unknotting is required for the replication of circular DNA as well as for various types of recombination in linear DNA.

Great length versus tiny breadth

The narrow breadth of the double helix makes it impossible to detect by conventional electron microscopy, except by heavy staining. At the same time, the DNA found in many cells can be macroscopic in length -- approximately 5 centimetres long for strands in a human chromosome. Consequently, cells must compact or "package" DNA to carry it within them. This is one of the functions of the chromosomes, which contain spool-like proteins known as histones, around which DNA winds.

Entropic stretching behavior

When DNA is in solution, it undergoes conformational fluctuations due to the energy available in the thermal bath. For entropic reasons, more floppy states are thermally accessible than stretched out states; for this reason, a single molecule of DNA stretches similarly to a rubber band. Using optical tweezers, the entropic stretching behavior of DNA has been studied and analyzed from a polymer physics perspective, and it has been found that DNA behaves like the Kratky-Porod worm-like chain model with a persistence length of about 53 nm. Furthermore, DNA undergoes a stretching phase transition at a force of 65 pN; above this force, DNA is thought to take the form that Linus Pauling originally hypothesized, with the phosphates in the middle and bases splayed outward. This proposed structure for overstretched DNA has been called "P-form DNA," in honor of Pauling.

Different helix geometries

The DNA helix can assume one of three slightly different geometries, of which the "B" form described by James D. Watson and Francis Crick is believed to predominate in cells. It is 2 nanometres wide and extends 3.4 nanometres per 10 bp of sequence. This is also the approximate length of sequence in which the double helix makes one complete turn about its axis. This frequency of twist (known as the helical pitch) depends largely on stacking forces that each base exerts on its neighbors in the chain.

Supercoiled DNA

The B form of the DNA helix twists 360° per 10.6 bp in the absence of strain. But many molecular biological processes can induce strain. A DNA segment with excess or insufficient helical twisting is referred to, respectively, as positively or negatively "supercoiled". DNA in vivo is typically negatively supercoiled, which facilitates the unwinding of the double-helix required for RNA transcription.

Sugar pucker

There are four conformations that the ribofuranose rings in nucleotides can acquire: # C-2' endo # C-2' exo # C-3' endo # C-3' exo Ribose is usually in C-3'endo, while deoxyribose is usually in the C-2' endo sugar pucker conformation. The A and B forms differ mainly in their sugar pucker. In the A form, the C3' configuration is above the sugar ring, whilst the C2' configuration is below it. Thus, the A form is described as "C3'-endo." Likewise, in the B form, the C2' configuration is above the sugar ring, whilst C3' is below; this is called "C2'-endo." Altered sugar puckering in A-DNA results in shortening the distance between adjacent phosphates by around one angstrom. This gives 11 to 12 base pairs to each helix in the DNA strand, instead of 10.5 in B-DNA. Sugar pucker gives uniform ribbon shape to DNA, a cylindrical open core, and also a deep major groove more narrow and pronounced that grooves found in B-DNA.

Conditions for formation of A and Z helices

The two other known double-helical forms of DNA, called A and Z, differ modestly in their geometry and dimensions. The A form appears likely to occur only in dehydrated samples of DNA, such as those used in crystallographic experiments, and possibly in hybrid pairings of DNA and RNA strands. Segments of DNA that cells have methylated for regulatory purposes may adopt the Z geometry, in which the strands turn about the helical axis like a mirror image of the B form.

Table of comparison of the properties of different helical forms

Non-helical forms

Other, including non-helical, forms of DNA have been described, for example a side-by-side (SBS) configuration. Indeed, it is far from certain that the B-form double helix is the dominant form in living cells.

Direction of DNA strands

The asymmetric shape and linkage of nucleotides means that a DNA strand always has a discernible orientation or directionality. Because of this directionality, close inspection of a double helix reveals that nucleotides are heading one way along one strand (the "ascending strand"), and the other way along the other strand (the "descending strand"). This arrangement of the strands is called antiparallel.

Chemical nomenclature (5' and 3')

For reasons of chemical nomenclature, people who work with DNA refer to the asymmetric ends of ("five prime" and "three prime"). Biologists and the DNA enzymes they use, predominantly read nucleotide sequences in the "5' to 3' direction". However, because chemically produced DNA is synthesized and manipulated in the opposite or in non-directional manners, the orientation should not be assumed. In a vertically oriented double helix, the 3' strand is said to be ascending while the 5' strand is said to be descending.

Sense and antisense

As a result of their antiparallel arrangement and the sequence-reading preferences of enzymes, even if both strands carried identical instead of complementary sequences, cells could properly translate only one of them. The other strand a cell can only read backwards. Molecular biologists call a sequence "sense" if it is translated or translatable, and they call its complement "antisense". It follows then, somewhat paradoxically, that the template for transcription is the antisense strand. The resulting transcript is an RNA replica of the sense strand and is itself sense.

Distinction between sense and antisense strands

A small proportion of genes in prokaryotes, and more in plasmids and viruses, blur the distinction made above between sense and antisense strands. Certain sequences of their genomes do double duty, encoding one protein when read 5' to 3' along one strand, and a second protein when read in the opposite direction (still 5' to 3') along the other strand. As a result, the genomes of these viruses are unusually compact for the number of genes they contain, which biologists view as an adaptation. This merely confirms that there is no biological distinction between the two strands of the double helix. Indeed, typically each strand of a DNA double helix will act as sense and antisense in different regions.

As viewed by topologists

Topologists like to note that the juxtaposition of the 3′ end of one DNA strand beside the 5′ end of the other at both ends of a double-helical segment makes the arrangement a "crab canon".

Single-stranded DNA (ssDNA) and repair of mutations

In some viruses DNA appears in a non-helical, single-stranded form. Because many of the DNA repair mechanisms of cells work only on paired bases, viruses that carry single-stranded DNA genomes mutate more frequently than they would otherwise. As a result, such species may adapt more rapidly to avoid extinction. The result would not be so favorable in more complicated and more slowly replicating organisms, however, which may explain why only viruses carry single-stranded DNA. These viruses presumably also benefit from the lower cost of replicating one strand versus two.

The history of DNA research

mutate at the University of Cambridge]] The discovery that DNA was the carrier of genetic information was a process that required many earlier discoveries. The existence of DNA was discovered in the mid 19th century. However, it was only in the early 20th century that researchers began suggesting that it might store genetic information. This was only accepted after the structure of DNA was elucidated by Watson and Crick in their 1953 Nature publication. Watson and Crick proposed the central dogma of molecular biology in 1957, describing the process whereby proteins are produced from nucleic DNA.

First isolation of DNA

Working in the 19th century, biochemists initially isolated DNA and RNA (mixed together) from cell nuclei. They were relatively quick to appreciate the polymeric nature of their "nucleic acid" isolates, but realized only later that nucleotides were of two types--one containing ribose and the other deoxyribose. It was this subsequent discovery that led to the identification and naming of DNA as a substance distinct from RNA. Friedrich Miescher (1844-1895) discovered a substance he called "nuclein" in 1869. Somewhat later, he isolated a pure sample of the material now known as DNA from the sperm of salmon, and in 1889 his pupil, Richard Altmann, named it "nucleic acid". This substance was found to exist only in the chromosomes. In 1929 Phoebus Levene at the Rockefeller Institute identified the components (the four bases, the sugar and the phosphate chain) and he showed that the components of DNA were linked in the order phosphate-sugar-base. He called each of these units a nucleotide and suggested the DNA molecule consisted of a string of nucleotide units linked together through the phosphate groups, which are the 'backbone' of the molecule. However Levene thought the chain was short and that the bases repeated in the same fixed order. Torbjorn Caspersson and Einar Hammersten showed that DNA was a polymer.

Establishing a link between heritable traits and chromosomes

Max Delbrück, Nikolai V. Timofeeff-Ressovsky, and Karl G. Zimmer published results in 1935 suggesting that chromosomes are very large molecules the structure of which can be changed by treatment with X-rays, and that by so changing their structure it was possible to change the heritable characteristics governed by those chromosomes. In 1937 William Astbury produced the first X-ray diffraction patterns from DNA. He was not able to propose the correct structure but the patterns showed that DNA had a regular structure and therefore it might be possible to deduce what this structure was. In 1943, Oswald Theodore Avery discovered that traits proper to the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria merely by making the killed "smooth" (S) form available to the live "rough" (R) form. Quite unexpectedly, the living R Pneumococcus bacteria were transformed into a new strain of the S form, and the transferred S characteristics turned out to be heritable. Avery called the medium of transfer of traits the transforming principle; he identified DNA as the transforming principle, and not protein as previously thought. In 1953, Alfred Hershey and Martha Chase did an experiment (Hershey-Chase experiment) that showed, in T2 phage, that DNA is the genetic material (Hershey shared the Nobel prize with Luria). genetic material double-helix pattern]] In 1944, the renowned physicist, Erwin Schrödinger, published a brief book entitled What is Life?, where he maintained that chromosomes contained what he called the "hereditary code-script" of life. He added: "But the term code-script is, of course, too narrow. The chromosome structures are at the same time instrumental in bringing about the development they foreshadow. They are law-code and executive power -- or, to use another simile, they are architect's plan and builder's craft -- in one." He conceived of these dual functional elements as being woven into the molecular structure of chromosomes. By understanding the exact molecular structure of the chromosomes one could hope to understand both the "architect's plan" and also how that plan was carried out through the "builder's craft." Three groups took up Schrödinger's challenge to work out the structure of the chromosomes and the question of how the segments of the chromosomes that were conceived to relate to specific traits could possibly do their jobs. Just how the presence of specific features in the molecular structure of chromosomes could produce traits and behaviors in living organisms was unimaginable at the time. Because chemical dissection of DNA samples always yielded the same four nucleotides, the chemical composition of DNA appeared simple, perhaps even uniform. Organisms, on the other hand, are fantastically complex individually and widely diverse collectively. Geneticists did not speak of genes as conveyors of "information" in such words, but if they had, they would not have hesitated to quantify the amount of information that genes need to convey as vast. The idea that information might reside in a chemical in the same way that it exists in text--as a finite alphabet of letters arranged in a sequence of unlimited length--had not yet been conceived. It would emerge upon the discovery of DNA's structure, but few researchers imagined that DNA's structure had much to say about genetics.

Discovery of the structure of DNA

In the 1950s, three groups made it their goal to determine the structure of DNA. The first group to start was at King's College London and was led Maurice Wilkins and was later joined by Rosalind Franklin. Another group consisting of Francis Crick and James D. Watson was at Cambridge. A third group was at CalTech and was led by Linus Pauling. Crick and Watson built physical models using metal rods and balls, in which they incorporated the known chemical structures of the nucleotides, as well as the known position of the linkages joining one nucleotide to the next along the polymer. At King's College Maurice Wilkins and Rosalind Franklin examined X-ray diffraction patterns of DNA fibers. Of the three groups, only the London group was able to produce good quality diffraction patterns and thus produce sufficient quantitative data about the structure X-ray diffraction

Discovery that DNA is helical

In 1948 Pauling discovered that many proteins included helical (see alpha helix) shapes. Pauling had deduced this structure from X-ray patterns. (Pauling was also later to suggest an incorrect three chain helical structure based on Astbury's data.) Even in the initial diffraction data from DNA by Maurice Wilkins, it was evident that the structure involved helices. But this insight was only a beginning. There remained the questions of how many strands came together, whether this number was the same for every helix, whether the bases pointed toward the helical axis or away, and ultimately what were the explicit angles and coordinates of all the bonds and atoms. Such questions motivated the modeling efforts of Watson and Crick.

Discovery that complementary nucleotides occur in equal proportions

In their modeling, Watson and Crick restricted themselves to what they saw as chemically and biologically reasonable. Still, the breadth of possibilities was very wide. A breakthrough occurred in 1952, when Erwin Chargaff visited Cambridge and inspired Crick with a description of experiments Chargaff had published in 1947. Chargaff had observed that the proportions of the four nucleotides vary between one DNA sample and the next, but that for particular pairs of nucleotides -- adenine and thymine, guanine and cytosine -- the two nucleotides are always present in equal proportions.

Watson and Crick's model

1947 Watson and Crick had begun to contemplate double helical arrangements, but they lacked information about the amount of twist (pitch) and the distance between the two strands. Rosalind Franklin had to disclose some of her findings for the Medical Research Council and Crick saw this material through Max Perutz's links to the MRC. Franklin's work confirmed a double helix that was on the outside of the molecule and also gave an insight into its symmetry, in particular that the two helical strands ran in opposite directions. Watson and Crick were again greatly assisted by more of Franklin's data. This is controversial because Franklin's critical X-ray pattern was shown to Watson and Crick without Franklin's knowledge or permission. Wilkins showed the famous Photo 51 to Watson at his lab immediately after Watson had been unsuccessful in asking Franklin to collaborate to beat Pauling in finding the structure. From the data in photograph 51 Watson and Crick were able to discern that not only was the distance between the two strands was constant, but also to measure its exact value of 2 nanometres. The same photograph also gave them the 3.4 nanometre-per-10 bp "pitch" of the helix. The final insight came when Crick and Watson saw that a complementary pairing of the bases could provide an explanation for Chargaff's puzzling finding. However the structure of the bases had been incorrectly guessed in the textbooks as the enol tautomer when they were more likely to be in the keto form. When Jerry Donohue pointed this fallacy out to Watson, Watson quickly realised that the pairs of adenine and thymine, and guanine and cytosine were almost identical in shape and so would provide equally sized 'rungs' between the two strands. With the base-pairing, the Watson and Crick quickly converged upon a model, which they announced before Franklin herself had published any of her work. Franklin was two steps away from the solution. She had not guessed the base-pairing and had not appreciated the implications of the symmetry that she had described. However she had been working almost alone and did not have regular contact with a partner like Crick and Watson, and with other experts such as Jerry Donohoe. Her notebooks show that she was aware both of Jerry Donohue's work concerning tautomeric forms of bases (she used the keto forms for three of the bases) and of Chargaff's work. The disclosure of Franklin's data to Watson has angered some people who believe Franklin did not receive due credit at the time and that she might have discovered the structure on her own before Crick and Watson. In Crick and Watson's famous paper in Nature in 1953, they said that their work had been stimulated by the work of Wilkins and Franklin, whereas it had been the basis of their work. However they had agreed with Wilkins and Franklin that they all should publish papers in the same issue of Nature in support of the proposed structure.

Publishing of the "Central Dogma"

Watson and Crick's model attracted great interest immediately upon its presentation. Arriving at their conclusion on February 21 1953, Watson and Crick made their first announcement on February 28. Their paper [http://www.nature.com/genomics/human/watson-crick/ 'A Structure for Deoxyribose Nucleic Acid'] was published on April 25. In an influential presentation in 1957, Crick laid out the "Central Dogma", which foretold the relationship between DNA, RNA, and proteins, and articulated the "sequence hypothesis." A critical confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 in the form of the Meselson-Stahl experiment. Work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of codons, and Har Gobind Khorana and others deciphered the genetic code not long afterward. These findings represent the birth of molecular biology. Watson, Crick, and Wilkins were awarded the 1962 Nobel Prize for Physiology or Medicine for discovering the molecular structure of DNA, by which time Franklin had died. Nobel prizes are not awarded posthumously; had she lived, the difficult decision over whom to jointly award the prize would have been complicated as the prize can only be shared between two or three. The process of the actual nomination is covered in Graeme Hunter's biography of Sir Lawrence Bragg, "Light is a Messenger" (pub. 2004)

Bibliography

- DNA: The Secret of Life, by James D. Watson. ISBN 0-375-41546-7
- The Double Helix: A Personal Account of the Discovery of the Structure of DNA (Norton Critical Editions), by James D. Watson. ISBN 0393950751

External links

- Extensive online guide to the life and work of Francis Crick, O.M. compiled by Martin Packer, Birmingham (England): http://www.packer34.freeserve.co.uk/rememberingfranciscrickacelebration.htm martin@packer34.freeserve.co.uk; recollections of Francis Crick (for publication) for the forthcoming biography would be very much appreciated as soon as possible.
- Listen to Francis Crick and James Watson talking on the BBC in 1962, 1972, and 1974: http://www.bbc.co.uk/bbcfour/audiointerviews/profilepages/crickwatson1.shtml
- [http://news.bbc.co.uk/1/hi/sci/tech/2949629.stm 17 April, 2003, BBC News: Most ancient DNA ever?]
- [http://www.whatsnextnetwork.com/health/index.php?cat=61 Latest Advances In Gene Research]
- [http://www.dnai.org DNA Interactive] (requires Macromedia Flash)
- [http://3dscience.com/3d_dna_models.asp Free 3d DNA model Images]
- [http://nist.rcsb.org/pdb/molecules/pdb23_1.html DNA: PDB molecule of the month]
- [http://www.fidelitysystems.com/Unlinked_DNA.html DNA under electron microscope]
- [http://www.myfirstbookaboutdna.com My First Book About DNA] Designed for children to learn more about DNA.
-
- [http://www.rotten.com/library/medicine/dna/ Rotten Library] articles on DNA
- Watson, James, and Francis Crick, "[http://biocrs.biomed.brown.edu/Books/Chapters/Ch%208/DH-Paper.html Molecular structure of nucleic acids], A structure for Deoxyribose Nucleic Acid". April 2, 1953. (paper on the structure of DNA) Category:Nucleic acids Category:Genetics
- ko:DNA ms:DNA ja:デオキシリボ核酸 simple:DNA th:ดีเอ็นเอ

University of Virginia

Established

1819

Founder

Thomas Jefferson

School type

Public University

President

John T. Casteen III

Location

Charlottesville, Va., USA

Enrollment

13,000 undergraduate
6,200 graduate

Faculty

2,015

Endowment

US $2.8 billion

Campus

World Heritage Site
1,682 acres

Mascot

Cavaliers

Athletics

Division I
23 varsity teams

33px

Website

[http://www.virginia.edu/ Virginia.edu]

33px

The University of Virginia (also referred to as U.Va. or simply Virginia for short) is a research university in Charlottesville, Virginia. It was established by founding father and third President of the United States, Thomas Jefferson. It is the only American college campus designated as a World Heritage Site by the United Nations Educational, Scientific and Cultural Organization. A public university, it attracts top students and academians, described in the 2006 edition of [http://www.usnews.com/usnews/edu/college/articles/brief/06uva_brief.php America's Best Colleges] as being "chock full of academic stars who turn down private schools like Duke, Princeton, and Cornell for, they say, a better value." The guide consistently ranks the university as the top doctoral-level educational institution in the state of Virginia.

History

Founded in 1819, the University of Virginia's inaugural banquet was held in 1824 in the presence of James Madison and the Marquis de Lafayette, and its first classes met in March 1825. At this time, it became the first university to offer students a full choice of elective courses, rather than a fixed schedule determined by school administrators. Jefferson explained: "This institution of my native state, the hobby of my old age, will be based on the illimitable freedom of the human mind to explore and to expose every subject susceptible of its contemplation." Jefferson passed away the following summer on July 4, 1826 – the 50th anniversary of the U.S. Declaration of Independence. U.S. Declaration of Independence His most innovative concept for the new university was based on a daring vision of higher education being completely separated from religious doctrine. One of the largest construction projects in North America up to that time, the new Grounds were centered upon a library (then housed in the Rotunda) rather than a church — distinguishing it from its peer universities in the English-speaking world, nearly all of which were dominated by one religious movement or another. Jefferson hosted Sunday dinners at his Monticello home for faculty and students, including Edgar Allan Poe, until his death. Some time before this occurred, Jefferson insisted that his grave bear the words FATHER OF THE UNIVERSITY OF VIRGINIA as one of three accomplishments during his lifetime by which he wished to be remembered. Many of America's political leaders have gravitated to the University of Virginia over the years. In 1826, fourth U.S. President James Madison became Rector of the University, at the same time America's fifth President James Monroe made his home on the Grounds and was a member of the Board of Visitors. 28th U.S. President Woodrow Wilson attended for one year the University of Virginia Law School, the same institution from which graduated Robert Kennedy, his son Robert Kennedy Jr., and his brother, Ted Kennedy. Other alumni in leadership roles have included three United States Supreme Court Justices, two Surgeons General, a Speaker of the House, a Senate Majority Leader, numerous Senators and Representatives, Secretaries of State, Defense, Energy, Transportation, Treasury, and the Navy, and the Secretary General of both NATO and the Council of the European Union. Unlike many other southern schools, the University of Virginia was kept open throughout the American Civil War. This was especially remarkable because Virginia was the site of more battles during this war than any other state. In March 1865, Union General George Armstrong Custer marched troops into Charlottesville, where faculty and community leaders convinced him to spare the university. Union troops camped on the Lawn and damaged many of the Pavilions, but left four days later without bloodshed. The University was then able to return to its educational routines. Union troops to found an institution of higher learning.]] Jefferson, ever the skeptic of central authority and bureaucracy, had originally decided the University of Virginia would have no President. Rather, this power was shared by a Rector and a Board of Visitors. As the nineteenth century drew to a close, it became obvious that this arrangement was incapable of adequately handling the many administrative and fundraising tasks that had become necessary and unavoidable in the interworkings of a modern university. In 1904, Edwin Alderman became the first President of the University of Virginia. In this position he embarked on a number of reforms for both the university and the state of Virginia's public educational systems in general. A reform specific to the University of Virginia was one of the first school-sponsored financial aid programs in all of higher learning and, though primitive by today's standards, it included a loan provision for those "needy young men" who were unable to pay. Initially controversial and opposed by many at what had become a very traditional school, Alderman's progressive ideas stood the test of time and he today remains the longest-serving President of the university's history, having served for nearly thirty years until his death in 1931. Alderman Library, a popular landmark among today's students, is his namesake. 1931–1836).]] "Public Ivy" is purportedly a term that was first coined to describe the University of Virginia. The term is attributed to Pulitzer and Nobel Prize winner William Faulkner at around the time the Ivy League was forming in the northeast. Some at the time thought the University should privatize a few of its schools and attempt to join them. Later, in 1957, Faulkner became writer-in-residence at the University, keeping open office hours until his death in 1962. Though all-white until 1950 and generally all-male until 1970 (women had for many years previous attended the education and nursing schools), the University of Virginia is now more diverse. The makeup of the Class of 2008 was 10% African-American, 14% Asian-American, 5% Hispanic, 5% Other and 5% International. Fewer than two-thirds identified themselves as being white. Eighty-five percent of the University's entering Class of 2009 were ranked in the top 10% of their graduating high school class and 56% were female. In 2004, the University of Virginia became the first public university in the United States to receive more of its funding from private sources than from the state with which it is associated. Thanks to a Charter initiative that recently passed the Virginia legislature, the University — and any other public universities in the state that choose to do so — will have greater autonomy over its own affairs. In the same year, the 100th anniversary of Alderman becoming President, the University announced the AccessUVa financial aid program. This innovative program, one of the first of its kind, guaranteed that U.Va. will meet 100% of a student's demonstrated need. It also provided low-income students (up to 200% of the poverty line – at the time about $37,700 for a family of four) with full grants to cover all of their educational needs. The program was an immediate success, and by 2005 was being studied and duplicated by other top public universities.

Grounds

2005 aviator for France, shot down before the U.S. joined the war effort.]] The University of Virginia stands on land purchased in 1788 by a Revolutionary War veteran, James Monroe, who would decades later become the fifth President of the United States. The Charlottesville farmland was purchased by the Board of Visitors of what was then Central College in 1817, while Monroe was beginning his first year in the White House. Guided by Thomas Jefferson, the Commonwealth of Virginia would charter the new university on January 25, 1819. Jefferson's original architectural design is centered around the Lawn, a grand, terraced green-space surrounded by residential and academic buildings. He called it the "Academical Village", and that name remains in use today to describe both the specific area of the Lawn and the larger university surrounding it. The principal building of the design, the Rotunda, is at the north end of the Lawn, and stands as one of the founder's greatest architectural achievements. It is half the height of the Pantheon in Rome, which was the primary inspiration for the building. The Lawn and the Rotunda were the model for many similar designs of "centralized green areas" at universities across the country (most notably those at Duke University in 1892, Johns Hopkins University in 1902, Rice University in 1910, Peabody College of Vanderbilt University in 1915, and Killian Court at MIT in 1916 — the last of which was coincidentally founded by William Barton Rogers, a former professor at U.Va.) Frank E. Grizzard, Jr., a scholar at the University of Virginia, has written the definitive book on the original academic buildings at the university. [http://etext.virginia.edu/jefferson/grizzard] William Barton Rogers William Barton Rogers William Barton Rogers William Barton Rogers Flanking both sides of the Rotunda and extending down the length of the Lawn are 10 "pavilions" interspersed with student rooms. Each has its own classical architectural style, as well as its own walled garden separated by uniquely Jeffersonian "serpentine walls." On October 27, 1895, the Rotunda burned to the ground with the unfortunate help of overzealous faculty member William "Reddy" Echols, who attempted to save it by throwing roughly 100 pounds (45 kg) of dynamite into the main fire in the hopes that the blast would separate the burning Annex from the main building. His last-ditch effort ultimately failed. (Perhaps ironically, one of the University's main honors student programs is named for him.) University officials swiftly approached celebrity architect Stanford White to rebuild the Rotunda. White took the charge further, redesigning the Rotunda interior — making it two floors instead of three, adding three buildings to the foot of the Lawn, and designing a President's House. He did omit rebuilding the Rotunda Annex, which had been built in 1853 to house classroom space. The classes formely occupying the annex were now moved to the South Lawn in White's new buildings. On June 10, 1940, U.S. President Franklin D. Roosevelt came to the University's Memorial Gymnasium to watch his son Franklin Jr. graduate, and to give the commencement address. Instead, there "in this University founded by the first great American teacher of democracy" he made his impromptu [ftp://webstorage2.mcpa.virginia.edu/library/nara/fdr/audiovisual/speeches/fdr_1940_0610.mp3 "Stab in the Back"] speech denouncing the act of Italy joining beside Nazi Germany to invade France on that day. (Graduation ceremonies are traditionally held on the Lawn, but rain had forced a move to "Mem Gym" for the Class of 1940.) Nearly two decades later, in 1958, Senator John F. Kennedy visited and spoke in the same space with brothers Robert Kennedy and Ted Kennedy, the latter of which was managing JFK's '58 Senatorial re-election campaign from his dormitory at the University of Virginia. In concert with the United States Bicentennial in 1976, Stanford White's changes to the Rotunda were removed and the building was returned to Jefferson's original design. Renovated according to the original plans, a three-story Rotunda opened on Jefferson's birthday, April 13, 1976. To commemorate the anniversary of America's independence, Britain's Queen Elizabeth II strolled the Lawn and lunched in the Dome Room of the Rotunda, one of five American sites she publicly visited. The Dalai Lama and Desmond Tutu, among many of humanity's spiritual leaders, graced the Lawn with their presence in 1998 while attending the University's Nobel Laureates Conference. In 2001, John Kluge donated 7,378 acres (30 km²) of additional lands to the University. Kluge wished for the core of the land to be developed by the university, and the surrounding land to be sold to fund an endowment supporting the core. A large part of the gift was soon sold to musician Dave Matthews, of the Dave Matthews Band, to be utilized in an organic farming project. It is unknown what the University will do with its "core" portion of the land. In the near future, the Lawn will change considerably. The McIntire School of Commerce will move to a new building adjoining Rouss Hall and the College's Economics department. At this time, Monroe Hall (current home of the McIntire School) will become part of the College. New Cabell Hall will be torn down, and in its place will be a technology-equipped classroom space that will straddle both sides of Jefferson Park Avenue. The Lawn will then extend to the space above where today is a faculty parking lot across the street. Being chosen for residence in one of the 54 Lawn rooms is considered prestigious. All undergraduate students who will graduate at the end of their year of residency are eligible to apply to live in one of the 47 rooms open to the general student body. Applications – which vary from year to year, but generally include a résumé, personal statement and responses to several questions – are reviewed by a reading committee and the top vote-getters are offered Lawn residency, with several alternates also given notice of potential residency. Five of the remaining seven rooms are "endowed" by organizations on Grounds: the Jefferson Literary and Debating Society (room 7), Trigon Engineering Society (room 17), Residence Staff (room 26), the Honor Committee (room 37) and the Kappa Sigma fraternity (room 46). These groups have their own selection process for choosing who will live in their Lawn room although the Vice President for Student Affairs renders final approval. The Gus Blagden "Good Guy" room (15) resident is chosen from a host of nominees and does not necessarily belonging to any particular group. Residency in the John K. Crispell memorial pre-med room (2) is usually granted to an outstanding pre-med student from among the group of 47 offered regular Lawn residency. Residence in the ten pavilions is also desirable. The University's Board of Visitors has final approval over which faculty members may live in a pavilion. Pavilion residency is typically offered as a three- or five-year contract with the option to renew. Pavilion residents are expected to interact with their younger "Lawnie" neighbors, as Jefferson intended. The Grounds of the University of Virginia, together with Monticello, are World Heritage Site #442. This honor is bestowed on no other American college campus and is shared with only three other man-made sites in the United States: the Statue of Liberty, Independence Hall, and Pueblo de Taos.

Academics

First in 1993, and again 8 times since, U.S. News and World Report ranked the University of Virginia as #1 (or tied for #1 with the University of California, Berkeley) among U.S. public universities. In the most recent (2006) edition, the undergraduate program at U.Va. currently ranks #23 (tied with Georgetown University) among national universities and #2 out of roughly 200 doctorate-granting public universities in the United States. In every edition of the report, the University of Virginia has been the highest ranking university, public or private, in the state of Virginia. The University of Virginia possesses a distinguished faculty, including a Nobel Laureate, 25 Guggenheim fellows, 26 Fulbright fellows, six National Endowment for the Humanities fellows, two Presidential Young Investigator Award winners, three Sloan award winners, three Packard Foundation Award winners, and the president of the NAACP. The University is known for its schools of Architecture, Business, Commerce, Law, Medicine, and Education, as well as for its departments of Art History, Astronomy, Astronomy-Physics, Biology, Biomedical Engineering, Chemistry, Computer Engineering, Computer Science, Economics, English, Finance, French, German, History, Management Information Systems, Physics, Politics, Psychology, Religious Studies, Spanish/Portuguese, and Systems Engineering. U.Va. hosts the National Radio Astronomy Observatory headquarters and is the lone American member of Universitas 21, an international consortium of research-intensive universities. The University of Virginia Library System holds 5,000,000 volumes. Its Electronic Text Center, established in 1992, has put 70,000 books online as well as 350,000 images that go with them. No university in the world can claim more electronic texts. These e-texts are open to anyone, and that is one reason that the electronic collection gets ten times as many visitors per day as do the physical libraries at the University. 1992 The University's faculty were particularly instrumental in the evolution of Internet networking and connectivity. Physics professor James McCarthy was the lead academic liaison to the government in the establishment of Suranet, and the University also participated in Arpanet and now participates in Internet2 and Abilene. In March of 1986, the University's website Virginia.edu became the first contribution to the World Wide Web originating from the state of Virginia. The University of Virginia offers numerous special scholars programs. The Echols and Rodman Scholars programs include 6-7% of undergraduate students and offer these students the "keys" to the university, in the form of advisors, separate first-year dorms, and priority course registration. Echols Scholars are also freed from the area requirements of the basic liberal arts curriculum. Perhaps the most selective program is the Jefferson Scholars Foundation, which offers full 4-year scholarships based on rigorous regional, international, and at-large competitions. Students are nominated by their respective high schools, and then have to pass various interviews before being invited, for a weekend, to participate in various tests of character, aptitude, and general suitability. Approximately 3% of those nominated are successful, making the scholarship one of the most competitive in the nation.

Organization

Virginia

Colleges and schools

- School of Architecture
- College of Arts & Sciences
- School of Continuing and Professional Studies
- Curry School of Education
- Darden Graduate School of Business Administration
- School of Engineering and Applied Science
- School of Law
- McIntire School of Commerce
- University of Virginia School of Medicine
- School of Nursing
- University of Virginia's College at Wise - former community college campus in Wise, Virginia

Athletics

The University of Virginia's sports teams are called the Cavaliers. The mascot is a mounted swordsman referring to the time when Virginia earned its nickname, the "Old Dominion." The Commonwealth was a hotbed of persons loyal to the English crown, called cavaliers in the days of the English Civil War and Interregnum. An unofficial moniker, the Wahoos, or 'Hoos for short, based on the University's rallying cry "Wah-hoo-wah!" is also commonly used. Though originally only used by the student body, both terms — Wahoos and Hoos — have come into wide use by the media as well. The school colors, adopted in 1888, are orange and navy blue. The athletic teams had previously worn silver and cardinal red, but those colors did not show up very well on dirty football fields as the school was sporting its first team. A mass meeting of the student body was called, and a star player showed up wearing a navy blue and orange scarf he had brought back from a University of Oxford summer boating expedition. The colors were chosen when another student pulled the scarf from the player's neck, waved it to the crowd and yelled: "How will this do?" (Exactly 100 years later in 1988, perhaps ironically, Oxford named their own American football club the "Cavaliers", and soon after the Virginia team adopted its "curved sabres" logo in 1994, the Oxford team followed suit.) 1994 When boxing was a major collegiate sport, Virginia's teams boxed in Memorial Gymnasium and went undefeated on a six-year run between 1932 and 1937, also winning national championships in 1938 and 1939. Virginia's athletic teams have participated in the Atlantic Coast Conference since the league's first year in 1953. Its men's basketball team has five times been part of the NCAA Elite Eight (1981, 1983, 1984, 1989, 1995), twice advancing to the Final Four (1981 and 1984). The Virginia Cavaliers football team has twice been honored as ACC Co-Champions (1989 with Duke, and 1995 with FSU). Women's cross country won national titles in 1981 and 1982. The soccer and lacrosse programs have both been tremendously successful. The Virginia men's soccer team has won five national championships, four consecutively (1989, 1991–1994). The lacrosse teams have won three national titles each. Men's lacrosse won national championships in 1972, 1999, and 2003; the women's lacrosse team won national titles in 1991, 1993, and 2004. Funding from benefactor Carl Smith created the foundation for the Cavalier Marching Band, which was introduced in 2004 and has grown to 230 pieces. This replaced the controversial Virginia Pep Band in its official capacity at athletic events. Scott Stadium sits across from the first-year dorms along Alderman Road, and it is home to the University of Virginia's most popular sport: football. Students, fans, and alumni generally cover themselves in orange clothing for the games, a trend which is slowly replacing the long-standing tradition of wearing sundresses or coat and tie at sporting events. The Cavaliers share the South's Oldest Rivalry with UNC and the schools have played 110 times, including every year since 1919. In a somewhat less historical but more bitterly contested rivalry, the team faces off with in-state foe Virginia Tech annually for the Commonwealth Cup, given since 1999 to the winner of this game played 86 times and each year since 1970. 1970 Basketball is also very popular at the University. At its recent height in the 1980s, the men's basketball team was better than perennial power Duke and second only to UNC in that decade's cumulative ACC standings. The 1990s and 2000s have seen a bit of a slide for the program to the middle of the pack in the conference, but U.Va. is currently building a new facility, John Paul Jones Arena ([http://minerva.acc.virginia.edu/athletics/jpj-arena.html construction webcam]), to replace the second-smallest — and for many years the smallest — facility in the ACC, University Hall. The new arena is scheduled to open in the Fall of 2006. Klöckner Stadium is home to several great programs, including Virginia men's soccer. More years than not, the University of Virginia fields one of the best squads in the country, and the program has, by far, the most successful history in the ultra-competitive Atlantic Coast Conference. Since ACC Tournament play began in 1987, Virginia has played in 14 out of 18 ACC Tournament championship matches, winning nine ACC titles (including 2003 and 2004), to go with their five NCAA Tournament championships. The man who built the U.Va. program, Bruce Arena, compiled an amazing 295-58-32 record before leaving in 1995 to coach D.C. United to their first two MLS championship seasons, and later the U.S. National Soccer Team to their best World Cup showing since 1930.

Student life

Student life at U.Va. is marked by a number of unique traditions that set the University apart from other American colleges. The campus of the University is referred to as "the Grounds," and seniors, juniors, sophomores and freshmen are instead called Fourth-, Third-, Second- and First-Years. A number of secret societies, most notably the Seven Society, Z Society, and IMP Society, have operated at the University for decades, leaving their painted marks on university buildings. Other significant secret societies include the Eli Banana Ribbon Society, the University's oldest secret society, the T.I.L.K.A's, the Purple Shadows, who commemorate Jefferson's birthday shortly after dawn on the Lawn each April 13, and the Rotunda Burning Society, who commemorate the Great Rotunda Fire. Not all the secret societies keep their identities unknown, but even those who don't hide themselves generally keep most of their good works and activities from the public eye. A positive attitude regarding the libraries exists among the students. A national publication's survey recently revealed that U.Va.'s students give their library system higher marks than students at any other school in the United States. The best-known library is Alderman Library for the humanities and social sciences, which contains seemingly endless stacks with many useful study nooks hidden among them. U.Va.'s renowned Small Special Collections Library feature one of the premier collections of American Literature in the country. Clemons Library, next to Alderman, is a popular study spot. Hundreds of students can be found gathered on its various quiet floors on any given night. Clark Hall, home of the Science & Engineering Library, also gets high marks. Relative to many other public and private universities, the University of Virginia has minimal red tape, paperwork, or bureaucracy. U.Va.'s ratio of staff-to-faculty is kept low, allowing for an efficient allocation of funds directly into paying faculty and educating its students. It is also a frequent observation that the faculty are very approachable and enjoy interacting with their students. Several of the