Ordinary cells of the body can be reprogrammed into stem cells

Nobel prize to Briton, Japanese for stem cell work

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  Enlarge PhotoAssociated Press/Kyodo News - Kyoto University Professor Shinya Yamanaka speaks during a news conference at Kyoto University in Kyoto, western Japan, Monday, Oct. 8, 2012, after learning that he and British …more 

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STOCKHOLM (AP) — A British researcher and a Japanese scientist won the Nobel Prize in physiology or medicine on Monday for discovering that ordinary cells of the body can be reprogrammed into stem cells, which then can turn into any kind of tissue — a discovery that may led to new treatments.

Scientists want to build on the work by John Gurdon and Shinya Yamanaka to create replacement tissues for treating diseases like Parkinson's and diabetes, and for studying the roots of diseases in the laboratory — without the ethical dilemma posed by embryonic stem cells.

In announcing the 8 million kronor ($1.2 million) award, the Nobel committee at Stockholm's Karolinska Institute said the discovery has "revolutionized our understanding of how cells and organisms develop."

Gurdon showed in 1962 — the year Yamanaka was born — that the DNA from specialized cells of frogs, like skin or intestinal cells, could be used to generate new tadpoles. That showed the DNA still had its ability to drive the formation of all cells of the body.
At the time, the discovery had "no obvious therapeutic benefit at all," Gurdon told reporters in London.
"It was almost 50 years before the value — the potential value — of that basic scientific research comes to light," he said.
In 1997, the cloning of Dolly the sheep by other scientists showed that the same process Gurdon discovered in frogs would work in mammals.

More than 40 years after Gurdon's discovery, in 2006, Yamanaka showed that a surprisingly simple recipe could turn mature cells back into primitive cells, which in turn could be prodded into different kinds of mature cells.

Basically, the primitive cells were the equivalent of embryonic stem cells, which had been embroiled in controversy because to get human embryonic cells, human embryos had to be destroyed. Yamanaka's method provided a way to get such primitive cells without destroying embryos.
"The discoveries of Gurdon and Yamanaka have shown that specialized cells can turn back the developmental clock under certain circumstances," the committee said. "These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine."
Just last week, Japanese scientists reported using Yamanaka's approach to turn skin cells from mice into eggs that produced baby mice.

Gurdon, 79, has served as a professor of cell biology at Cambridge University's Magdalene College and is currently at the Gurdon Institute in Cambridge, which he founded. Yamanaka, 50, worked at the Gladstone Institute in San Francisco and Nara Institute of Science and Technology in Japan. He is currently at Kyoto University and also affiliated with the Gladstone Institute. Yamanaka is the first Japanese scientist to win the Nobel medicine award since 1987.

Yamanaka told Japanese broadcaster NHK that he was at home doing chores on Monday when he got the call from Stockholm.
"Even though we have received this prize we have not really accomplished what we need to. I feel a deep sense of duty and responsibility," Yamanaka said.
Choosing Yamanaka as a Nobel winner just six years after his discovery was unusual. The Nobel committees typically reward research done more than a decade before, to make sure it has stood the test of time.
In 2010, the Nobel Prize in physics went to two researchers whose discoveries were also published six years earlier. In 2006, two American scientists won the medicine prize eight years after their work was published.
Prize committee member Juleen Zierath said Gurdon and Yamanaka's discoveries, which also earned them a Lasker award for basic research in 2009, could hold "immense potential," including in developing treatments for Parkinson's disease and in making cells that produce insulin. However, she added that therapeutic implications are still far away.
The idea of reprograming cells has also been put to work in basic research on disease, through an approach sometimes called "disease in a dish."

The reprogramming allows scientists to create particular kinds of tissue they want to study, like lung tissue for studying cystic fibrosis, or brain tissue for Huntington's disease. By reprogramming cells from patients with a particular disease, they can create new tissue with the same genetic background, and study it in the lab. That can give new insights into the roots of the problem.

In addition, that approach allows them to screen drugs in the lab for possible new medicines.

Experts welcomed the announcement, praising the duo for their groundbreaking and influential discoveries in a field riddled with ethical debates.

"Everyone who works on developmental biology and on the understanding of disease mechanisms will applaud these excellent and clear choices for the Nobel Prizes," said John Hardy, professor of Neuroscience at University College London. "Countless labs' work builds on the breakthroughs they have pioneered."

Yamanaka deserves extra credit for overcoming fierce objections to the creation of embryos for research, reviving the field, said Julian Savulescu, director of Oxford University's Uehiro Centre for Practical Ethics.

"Yamanaka has taken people's ethical concerns seriously about embryo research and modified the trajectory of research into a path that is acceptable for all," Savulescu said. "He deserves not only a Nobel Prize for Medicine, but a Nobel Prize for Ethics."

Goran Hansson, the secretary of the prize committee, said he had reached both winners by phone before the announcement. He said they were looking forward to coming to Stockholm to collect the award in a ceremony on Dec. 10, the anniversary of prize founder Alfred Nobel's death in 1896.
The medicine award was the first Nobel Prize to be announced this year. The physics award will be announced Tuesday, followed by chemistry on Wednesday, literature on Thursday and the Nobel Peace Prize on Friday.

The economics prize, which was not among the original awards, but was established by the Swedish central bank in 1968, will be announced on Oct. 15.

______

Associated Press science writer Malcolm Ritter in New York; AP writers Cassandra Vinograd and Raphael Satter in London; and AP writer Elaine Kurtenbach in Tokyo contributed to this report.

'God Particle' is key to universe is it

What is the Higgs boson and why is it important?

By Nick Thompson, CNN

July 4, 2012 -- Updated 0727 GMT (1527 HKT)

STORY HIGHLIGHTS

• Scientists say they've found new evidence the Higgs boson exists
• The so-called "God particle" is thought to be a building block of the universe
• The theoretical particle is key to understanding how universe works, experts say

(CNN) -- Scientists say they are closer to proving the existence of the Higgs boson -- a never-before-seen subatomic particle long thought to be a fundamental building block of the universe.

Researchers at the Large Hadron Collider under the Alps are unveiling their latest results on the so-called "God particle" at an eagerly awaited seminar at the CERN particle physics laboratory in Geneva, Switzerland.

Experts say finding the elusive particle would rank as one of the top scientific achievements of the past 50 years.

What is the Higgs boson?

The Standard Model of particle physics lays out the basics of how elementary particles and forces interact in the universe. But the theory crucially fails to explain how particles actually get their mass.

Particles, or bits of matter, range in size and can be larger or smaller than atoms. Electrons, protons and neutrons, for instance, are the subatomic particles that make up an atom.

Scientists believe that the Higgs boson is the particle that gives all matter its mass.

Read more: The woman at the edge of physics

Experts know that elementary particles like quarks and electrons are the foundation upon which all matter in the universe is built. They believe the elusive Higgs boson gives the particles mass and fills in one of the key holes in modern physics.

Higgs boson is the last missing piece of our current understanding of the most fundamental nature of the universe.
Physicist Martin Archer

How does the Higgs boson work?

The Higgs boson is part of a theory first proposed by physicist Peter Higgs and others in the 1960s to explain how particles obtain mass.

The theory proposes that a so-called Higgs energy field exists everywhere in the universe. As particles zoom around in this field, they interact with and attract Higgs bosons, which cluster around the particles in varying numbers.

Imagine the universe like a party. Relatively unknown guests at the party can pass quickly through the room unnoticed; more popular guests will attract groups of people (the Higgs bosons) who will then slow their movement through the room.

The speed of particles moving through the Higgs field works much in the same way. Certain particles will attract larger clusters of Higgs bosons -- and the more Higgs bosons a particle attracts, the greater its mass will be.

Why is finding the Higgs boson so important?

While finding the Higgs boson won't tell us everything we need to know about how the universe works, it will fill in a huge hole in the Standard Model that has existed for more than 50 years, according to experts.

"The Higgs boson is the last missing piece of our current understanding of the most fundamental nature of the universe," Martin Archer, a physicist at Imperial College in London, told CNN.

"Only now with the LHC [Large Hadron Collider] are we able to really tick that box off and say 'This is how the universe works, or at least we think it does'."

"It's not the be all and end all -- but in terms of what can we say practically about the world and how the world is, it actually tells us a lot."

Gordon Kane, director of the Michigan Center for Theoretical Physics, added that finding evidence of the Higgs boson would be a "very wonderful success of science and of people for four centuries."

Why is the Higgs boson called the "God particle?"

The popular nickname for the elusive particle was created for the title of a book by Nobel Prize winning physicist Leon Lederman -- reportedly against his will, as Lederman has said he wanted to call it the "Goddamn Particle" because "nobody could find the thing."

"'God particle' is a nickname I don't really like," says Archer. "It's nothing to do with religion -- the only (theoretical) similarity is you're seeing something that's a field that's everywhere, in all spaces."

How are scientists searching for the Higgs boson?

For the past eighteen months scientists have searched for the Higgs boson by smashing protons together at high energy in the $10 billion Large Hadron Collider (LHC) at CERN in Geneva, Switzerland.

If we don't see [Higgs], it means the universe is more complicated than we thought.
Physicist Martin Archer

Inside the LHC, which is located 328 feet underground in a 17-mile tunnel and is the most powerful particle accelerator ever built, high speed proton collisions generate a range of even smaller particles that scientists sift through in search of a signal in the data suggesting the existence of the Higgs boson.

"You're just hoping that somewhere in these collisions that you see something ... some sort of a statistical bump," says Archer.

If Higgs bosons exist, they are elusive, popping up and then disappearing again quickly. It means, says Archer, that scientists at the LHC will only be able to observe their decaying remnants.

It has taken years for scientists to narrow down the range of mass in which they believed the Higgs boson could exist -- but during the past year a statistical bump suggests they're on the right track.

"Now they're starting to get a bump, the scientists should be able to get that result more and more," says Archer.

What if scientists don't find the Higgs boson?

The general consensus among physics academics is that the Higgs field and boson exists, according to Archer.

"It just makes sense within the framework that we've got everything set up in, given that everything else that we can describe and we can see seems to be described in this simple way," says Archer.

Nearly every scientist believes that the Large Hadron Collider will either prove or disprove the existence of the Higgs boson once and for all -- so if the LHC doesn't find it, it doesn't exist, experts say.

Martin Archer believes a failure to find the Higgs boson would be even more exciting than discovering the elusive particle.

"If we don't see it, it actually means that the universe at the most fundamental level is more complicated than we thought," says Archer, "and therefore maybe the way we've been attacking physics isn't right."

Proteomics might be the magic bullet

Protein discovery could lead to new HIV drugs

January 27, 2012 in HIV & AIDS

(Medical Xpress) -- A team of researchers at the Johns Hopkins Bloomberg School of Public Health recently discovered a new protein that enables HIV to destroy human cells. The finding provides scientists with a critical glimpse into the complex interactions between HIV proteins and human proteins, a discovery that could potentially lead to new HIV drug therapies. The study was published in the January 19, 2012 issue of Nature.

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HIV is a small but efficient pathogen that includes about 15 proteins which can act in various combinations with the more than 30,000 proteins in the human cell. APOBEC3G is a human protein that has the power to mutate HIV’s genome and prevent infection. However, an HIV protein called HIV-1 viral infectivity factor (Vif) typically associates itself with and degrades APOBEC3G before it can do its job.
Focusing on the interaction between Vif and APOBEC3G, researchers found that another protein called CBF-ß was a key factor needed in order for the degradation of APOBEC3G to take place.
“I’ve been working in this field for over 25 years and I am certain that there is still even more left to this story,” explained Xiao-Fang Yu, MD, DSc, professor in the Bloomberg School’s W. Harry Feinstone Department of Molecular Microbiology and Immunology and lead author of the study. “This is an exciting time to be in HIV research.”
“The identification of CBF-ß is only one piece of the puzzle, but it’s an important one,” said Sean L. Evans, a PhD candidate in the Department of Molecular Microbiology and Immunology and one author of the study. “The human protein APOBEC3G is designed to weaken HIV, and the virus has evolved a mechanism for defeating this anti-viral factor.”
There are currently more than 20 approved HIV antiviral therapies, some of which target protein interactions between the virus and humans. However, drug failure and the emergence of drug-resistant variants make it necessary to further this research and continually expand the number of HIV drugs available.
The next step, now that scientists have identified CBF-ß, will be to test various inhibitors and potential drug therapies to determine which ones disrupt the interaction between CBF-ß and Vif, and, therefore, which ones can prevent the degradation of APOBEC3G.
“Understanding these interactions is essential to the intelligent design of drugs that can fight HIV,” continued Evans. “If we can stop Vif from degrading APOBEC3G, HIV would be severely crippled.”
The study was completed in partnership with the First Hospital of Jilin University in China and was funded by the National Institutes of Health, the Chinese Ministry of Education and the Chinese Ministry of Science and Technology, as well as the Key Laboratory of Molecular Virology.
Provided by Johns Hopkins Bloomberg School of Public Health

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war war war

I know not with what weapons World War III will be fought, but World War IV will be fought with sticks and stones.
Albert Einstein

Very gun that is made, every warship launched, every rocket fired signifies in the final sense, a theft from those who hunger and are not fed, those who are cold and are not clothed. This world in arms is not spending money alone. It is spending the sweat of its laborers, the genius of its scientists, the hopes of its children. This is not a way of life at all in any true sense. Under the clouds of war, it is humanity hanging on a cross of iron.
Dwight Eisenhower 1953 speech

Artificial intelligence course for those intrested

Stanford CS221: Introduction to Artificial Intelligence Professors Sebastian Thrun and Peter Norvig

Outline Schedule Online

Overview CS221 is the introductory course into the field of Artificial Intelligence at Stanford University. It covers basic elements of AI, such as knowledge representation, inference, machine learning, planning and game playing, information retrieval, and computer vision and robotics. CS221 is a broad course aimed to teach students the very basics of modern AI. It is prerequisite to many other, more specialized AI classes at Stanford University. Instructors Professors Peter Novig and Sebastian Thrun took over CS221 from Professor Andrew Y. Ng in 2010. Peter Norvig is author of the celebrated textbook Artificial Intelligence: A Modern Approach. He is also Director of Research at Google. Thrun is well known for his work on robotics and self-driving cars (His team won the DARPA Grand Challenge). Thrun is research professor at Stanford and a Google Fellow. He is one of the youngest individuals ever elected into the National Academy of Engineering (at age 39). Who Should Attend? With an in-class enrollment of nearly 200 students, CS221 is one of the largest courses taught at Stanford University, across all departments and all disciplines. It is included in the core curriculum of several degree programs at Stanford. The course is tailored towards advanced undergraduate or early graduate students, new to Artificial Intelligence, who wish to learn about the excitement in the field. The course indtroduce a wealth of topics in AI, many of which are then subject of more specialized follow-on classes at Stanford. This version of CS221 will also be offered online. Using some new technology, the instuctors will offer materials used in this class to online students, free of charge. It is their objective to offer identical homework assignments, quizzes, and exams in both versions of this course. Students taking the online version will therefore be graded according to the same grading criteria as students taking CS221 at Stanford. However, to receive Stanford credit, the course has to be taken through Stanford; and students have to be registered at Stanford University. Online student will only get a certificate in the name of the instructors, but no official Stanford certificate. Course Description This course is 10 weeks long. The in-class version starts Tue, Sept 27. The online version begins Mon, Oct 2, 2011. The course consists of Approximately 20 lectures. Each lecture includes quizzes that we ask you to do, but which are not counted towards the final grade of this class. Instead, you can see the right answer to each quizz right after submitting your answers. Approximately 8 homework assignments. Those are just like our quizzes, and if you do well in the quizzes, you should do well in the assignments. However, we won't show you the correct answer only with a few days delay, to discourage cheating. One midterm and one final exam. These are like extended quizzes, covering all subject areas of the course discussed so far. The exams will also check your general knowledge about topics covered in the reading materials (the book). The central objective is to teach basic methods in AI, and to convey enthusiasm for the field. AI has emerged as one of the most impactful disciplines in science and technology. Google, for example, is massively run on AI. Students passing this course should be proficient basic methods of AI, and have a broad overview of the field.q Passing Requirements To pass this course, you have to attend (or watch online) all lectures. You have to turn in all homework assignments and exams. We grant a total of six "late days" which can be used to turn an assignment or an exam in late. Stanford has a strong Honor's Code. We expect you to honor this code. Violations may lead to disciplinary action against you. Prerequisites A solid understanding of probability and linear algebra will be required.

this is so amazing discovery!

HIV Mutates to Death With New Drug Eric Bland, Discovery News

 

HIV | Discovery News Video

 

Feb. 9, 2009 -- HIV is notorious for its ability to mutate and evade drugs designed to destroy it. Now scientists are testing a new drug that actually speeds up that rate of change in the hope that the deadly virus will mutate itself to death.
"The HIV virus is so dependent on mutation that it really lives on the edge of existence," said John Reno, Chief Operating Officer for Koronis Pharmaceuticals, the company developing a drug called KP-1461. "But we figured that if we could increase this mutation rate, [HIV] might finally fall off that edge."
KP-1461 is a mutagen, meaning it encourages mutation, and has been in development for several years by the scientists at Koronis Pharmaceuticals.
When any cell or virus reproduces, there are inevitable mistakes, or mutations, as the four building blocks of DNA pair together into a double helix. Usually, the base adenine pairs up with the base thymine, and one called guanine pairs with cytosine.
Related Content:

---

• Discovery Tech: Get the Wide Angle on Synthetic Biology
• Gold Nanoparticles Resurrect Failed HIV Drug
• HowStuffWorks.com: The Speed of Mutation
• More Discovery News

---

KP-1461 looks like both thymine and cytosine, and will occasionally replace one of the normal bases in DNA, causing more errors.
"It really mucks up the genetic information inside the viral DNA," said Reno.
Disrupting HIV's replication doesn't directly destroy the virus, however, at least not immediately. It's the build-up of genetic mistakes that finally destroys it.

Next »21« Previous

transposons

Transposons: Mobile DNA

Class II Transposons Miniature Inverted-repeat Transposable Elements (MITEs) in maize in Drosophila in bacteria Retrotransposons (Class I) HIV-1 LINEs (Long interspersed elements) SINEs (Short interspersed elements) Transposons and Mutations What good are transposons? Transposons and the C-value Paradox

Transposons are segments of DNA that can move around to different positions in the genome of a single cell. In the process, they may

• cause mutations
• increase (or decrease) the amount of DNA in the genome of the cell, and if the cell is the precursor of a gamete, in the genomes of any descendants.

These mobile segments of DNA are sometimes called "jumping genes".
There are two distinct types:

• Class II transposons. These consist of DNA that moves directly from place to place.
• Class I transposons. These are retrotransposons that
  • first transcribe the DNA into RNA and then
  • use reverse transcriptase to make a DNA copy of the RNA to insert in a new location.

Class II Transposons

Class II transposons move by a "cut and paste" process: the transposon is cut out of its location (like command/control-X on your computer) and inserted into a new location (command/control-V).
This process requires an enzyme — a transposase — that is encoded within some of these transposons.
Transposase binds to:

• both ends of the transposon, which consist of inverted repeats; that is, identical sequences reading in opposite directions.
• a sequence of DNA that makes up the target site. Some transposases require a specific sequence as their target site; others can insert the transposon anywhere in the genome.

The DNA at the target site is cut in an offset manner (like the "sticky ends" produced by some restriction enzymes [Examples]).
After the transposon is ligated to the host DNA, the gaps are filled in by Watson-Crick base pairing. This creates identical direct repeats at each end of the transposon.
Often transposons lose their gene for transposase. But as long as somewhere in the cell there is a transposon that can synthesize the enzyme, their inverted repeats are recognized and they, too, can be moved to a new location.

Miniature Inverted-repeat Transposable Elements (MITEs)

The recent completion of the genome sequence of rice and C. elegans has revealed that their genomes contain thousands of copies of a recurring motif consisting of

• almost identical sequences of about 400 base pairs flanked by
• characteristic inverted repeats of about 15 base pairs such as
  5' GGCCAGTCACAATGG..~400 nt..CCATTGTGACTGGCC 3'
  3' CCGGTCAGTGTTACC..~400 nt..GGTAACACTGACCGG 5'
  

MITEs are too small to encode any protein. Just how they are copied and moved to new locations is still uncertain. Probably larger transposons that

• do encode the necessary enzyme and
• recognize the same inverted repeats

are responsible. There are over 100,000 MITEs in the rice genome (representing some 6% of the total genome). Some of the mutations found in certain strains of rice are caused by the insertion of a MITE in the gene.
MITEs have also been found in the genomes of humans, Xenopus, and apples.

Transposons in maize

The first transposons were discovered in the 1940s by Barbara McClintock who worked with maize (Zea mays, called "corn" in the U.S.). She found that they were responsible for a variety of types of gene mutations, usually

• insertions and deletions (indels)
• translocations

Some of the mutations (c, bz) used as examples of how gene loci are mapped on the chromosome were caused by transposons. [Link]

In developing somatic tissues like corn kernels, a mutation (e.g., c) that alters color will be passed on to all the descendant cells. This produces the variegated pattern which is so prized in "Indian corn". (Photo courtesy of Whalls Farms.)
It took about 40 years for other scientists to fully appreciate the significance of Barbara McClintock's discoveries. She was finally awarded a Nobel Prize in 1983.

Transposons in Drosophila

P elements are Class II transposons found in Drosophila. They do little harm because expression of their transposase gene is usually repressed. However, when male flies with P elements mate with female flies lacking them, the transposase becomes active in the germline producing so many mutations that their offspring are sterile.
In nature this is no longer a problem. P elements seem to have first appeared in Drosophila melanogaster about 50 years ago. Since then, they have spread through every population of the species. Today flies lacking P elements can only be found in old strains maintained in the laboratory.
P elements have provided valuable tools for Drosophila geneticists. Transgenic flies containing any desired gene can be produced by injecting the early embryo with an engineered P element containing that gene.
Other transposons are being studied for their ability to create transgenic insects of agricultural and public health importance.

Transposons in bacteria

Some transposons in bacteria carry — in addition to the gene for transposase — genes for one or more (usually more) proteins imparting resistance to antibiotics. When such a transposon is incorporated in a plasmid, it can leave the host cell and move to another. This is the way that the alarming phenomenon of multidrug antibiotic resistance spreads so rapidly. Transposition in these cases occurs by a "copy and paste" (command/control-C -> command/control-V) mechanism. This requires an additional enzyme — a resolvase — that is also encoded in the transposon itself. The original transposon remains at the original site while its copy is inserted at a new site.

Retrotransposons

Retrotransposons also move by a "copy and paste" mechanism but in contrast to the transposons described above, the copy is made of RNA, not DNA.
The RNA copies are then transcribed back into DNA — using a reverse transcriptase — and these are inserted into new locations in the genome.
Many retrotransposons have long terminal repeats (LTRs) at their ends that may contain over 1000 base pairs in each.
Like DNA transposons, retrotransposons generate direct repeats at their new sites of insertion. In fact, it is the presence of these direct repeats that often is the clue that the intervening stretch of DNA arrived there by retrotransposition. 42% of the entire human genome consists of retrotransposons.

HIV-1

HIV-1 — the cause of AIDS — and other human retroviruses (e.g., HTLV-1, the human T-cell leukemia virus) behave like retrotransposons. The RNA genome of HIV-1 contains a gene for

• reverse transcriptase and one for
• integrase. The integrase serves the same function as the transposases of DNA transposons. The DNA copies can be inserted anywhere in the genome.

Molecules of both enzymes are incorporated in the virus particle.

Link to an illustration and further discussion.

LINEs (Long interspersed elements)

• The human genome contains some 868,000 LINEs (representing ~17% of the genome).
• Most of these belong to a family called LINE-1 (L1).
• These L1 elements are DNA sequences that range in length from a few hundred to as many as 9,000 base pairs.
• Only about 50 L1 elements are functional "genes"; that is, can be transcribed and translated.
• The functional L1 elements are about 6,500 bp in length and encode three proteins, including
  • an endonuclease that cuts DNA and a
  • reverse transcriptase that makes a DNA copy of an RNA transcript.
• L1 activity proceeds as follows:
  • RNA polymerase II transcribes the L1 DNA into RNA.
  • The RNA is translated by ribosomes in the cytoplasm into the proteins.
  • The proteins and RNA join together and reenter the nucleus.
  • The endonuclease cuts a strand of "target" DNA, often in the intron of a gene.
  • The reverse transcriptase copies the L1 RNA into L1 DNA which is inserted into the target DNA forming a new L1 element there.

Through this copy-paste mechanism, the number of LINEs can increase in the genome.
The diversity of LINEs between individual human genomes make them useful markers for DNA "fingerprinting".
Variation occurs in the length of L1 elements:

• Transcription of an active L1 element sometimes continues downstream into additional DNA producing a longer transposed element.
• Reverse transcription of L1 RNA often concludes prematurely and produces a shortened transposed element.

While L1 elements are not functional, they may play a role in regulating the efficiency of transcription of the gene in which they reside (see below). Occasionally, L1 activity makes and inserts a copy of a cellular mRNA (thus a natural cDNA). Lacking introns as well as the necessary control elements like promoters, these genes are not expressed. They represent one category of pseudogene.

SINEs (Short interspersed elements)

SINEs are short DNA sequences (100–400 base pairs) that represent reverse-transcribed RNA molecules originally transcribed by RNA polymerase III; that is, molecules of tRNA, 5S rRNA, and some other small nuclear RNAs. The most abundant SINEs are the Alu elements. There are over one million copies in the human genome (representing 10.6% of our total DNA).
Alu elements consist of a sequence of 300 base pairs containing a site that is recognized by the restriction enzyme AluI. They appear to be reverse transcripts of 7S RNA, part of the signal recognition particle.
Most SINEs do not encode any functional molecules and depend on the machinery of active L1 elements to be transposed; that is, copied and pasted in new locations.

Transposons and Mutations

Transposons are mutagens. They can cause mutations in several ways:

• If a transposon inserts itself into a functional gene, it will probably damage it. Insertion into exons, introns, and even into DNA flanking the genes (which may contain promoters and enhancers) can destroy or alter the gene's activity.

  The insertion of a retrotransposon in the DNA flanking a gene for pigment synthesis is thought to have produced white grapes from a black-skinned ancestor. Later, the loss of that retrotransposon produced the red-skinned grape varieties cultivated today.

• Faulty repair of the gap left at the old site (in cut and paste transposition) can lead to mutation there.
• The presence of a string of identical repeated sequences presents a problem for precise pairing during meiosis. How is the third, say, of a string of five Alu sequences on the "invading strand" of one chromatid going to ensure that it pairs with the third sequence in the other strand? If it accidentally pairs with one of the other Alu sequences, the result will be an unequal crossover — one of the commonest causes of duplications.

  Link to an example of a mutation caused by unequal crossing over.

SINEs (mostly Alu sequences) and LINEs cause only a small percentage of human mutations. (There may even be a mechanism by which they avoid inserting themselves into functional genes.) However, they have been found to be the cause of the mutations responsible for some cases of human genetic diseases, including:

• Hemophilia A (Factor VIII gene) and Hemophilia B [Factor IX gene]
• X-linked severe combined immunodeficiency (SCID) [gene for part of the IL-2 receptor]
• porphyria
• predisposition to colon polyps and cancer [APC gene]
• Duchenne muscular dystrophy [dystrophin gene]

What good are transposons?

We don't know.
They have been called "junk" DNA and "selfish" DNA.

• "selfish" because their only function seems to make more copies of themselves and
• "junk" because there is no obvious benefit to their host.

Because of the sequence similarities of all the LINEs and SINEs, they also make up a large portion of the "repetitive DNA" of the cell.
Retrotransposons cannot be so selfish that they reduce the survival of their host. Perhaps, they even confer some benefit.
Some possibilities:

• Retrotransposons often carry some additional sequences at their 3' end as they insert into a new location. Perhaps these occasionally create new combinations of exons, promoters, and enhancers that benefit the host. Example:
  
  • Thousands of our Alu elements occur in the introns of genes.
  • Some of these contain sequences that when transcribed into the primary transcript are recognized by the spliceosome.
  • These can then be spliced into the mature mRNA creating a
  • new exon, which will be transcribed into a new protein product.
  • Alternative splicing can provide not only the new mRNA (and thus protein) but also the old.
  • In this way, nature can try out new proteins without the risk of abandoning the tried-and-true old one.
  
  
• L1 elements inserted into the introns of functional genes reduce the transcription of those genes without harming the gene product — the longer the L1 element, the lower the level of gene expression. Some 79% of our genes contain L1 elements, and perhaps they are a mechanism for establishing the baseline level of gene activity.
• Telomerase, the enzyme essential for maintaining chromosome length, is closely related to the reverse transcriptase of LINEs and may have evolved from it.
• RAG-1 and RAG-2. The proteins encoded by these genes are needed to assemble the repertoire of antibodies and T-cells receptors (TCRs) used by the adaptive immune system [Link]. The mechanism [Link] resembles that of the cut and paste method of Class II transposons , and the RAG genes may have evolved from them. If so, the event occurred some 450 million years ago when the jawed vertebrates evolved from jawless ancestors [Link]. Only jawed vertebrates have the RAG-1 and RAG-2 genes.
• In Drosophila, the insertion of transposons into genes has been linked to the development of resistance to DDT and organophosphate insecticides.

Transposons and the C-value Paradox

• The genome of Arabidopsis thaliana contains ~1.2 x 10⁸ base pairs (bp) of DNA. About 14% of this consists of transposons; the rest functional genes (about 28,000 of them).
• The maize (corn) genome contains 20 times more DNA (2.4 x 10⁹ bp) but surely has no need for 20 times as many genes. In fact, 60% of the corn genome is made up of transposons. (The figure for humans is 42%.)
• Most of the 2.5 x 10¹¹ bp of DNA in the genome of Psilotum nudum is presumably "junk" DNA.

So it seems likely that the lack of an association between size of genome and number of functional genes — the C-value paradox — is caused by the amount of transposon DNA accumulated in the genome.

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13 June 2011