Posts about dna

Epigenetics, Scientific Inquiry and Uncertainty

Science is full of fascinating ideas. Epigenetics is one area I find particularly interesting. This previous post has a few links to learning more: DNA Passed to Descendants Changed by Your Life.

Angela Saini is one 109 people I follow on Twitter. I don’t see the point in “following” people on Twitter that you have no interest in, I only follow the small number of people that post Tweets I want to read.

In, Epigenetics: genes, environment and the generation game, Angela Saini looks at the confused state of current scientific understand now. It is very difficult to tell if, and if so, to what extent, epigenetic inheritance happens in people.

Professor Azim Surani, a leading developmental biologist and geneticist at the University of Cambridge, adds that while there is good evidence that epigenetic inheritance happens in plants and worms, mammals have very different biology. Surani’s lab carried out thorough studies on how epigenetic information was erased in developing mouse embryos and found that “surprisingly little gets through” the reprogramming process.

Professor Timothy Bestor, a geneticist at Columbia University in New York, is far more damning, claiming that the entire field has been grossly overhyped. “It’s an extremely fashionable topic right now. It’s very easy to get studies on transgenerational epigenetic inheritance published,” he says, adding that all this excitement has lowered critical standards.

Related: Epigenetic Effects on DNA from Living Conditions in Childhood Persist Well Into Middle AgeMedical Study Findings too Often Fail to Provide Us Useful KnowledgeScientific Inquiry Process Finds That Komodo Dragons Don’t have a Toxic Bite After All

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DNA Contains Gene Control Instructions

Scientists discover double meaning in genetic code

Scientists have discovered a second code hiding within DNA. This second code contains information that changes how scientists read the instructions contained in DNA and interpret mutations to make sense of health and disease.

“For over 40 years we have assumed that DNA changes affecting the genetic code solely impact how proteins are made,” said Stamatoyannopoulos. “Now we know that this basic assumption about reading the human genome missed half of the picture. These new findings highlight that DNA is an incredibly powerful information storage device, which nature has fully exploited in unexpected ways.”

The genetic code uses a 64-letter alphabet called codons. The UW team discovered that some codons, which they called duons, can have two meanings, one related to protein sequence, and one related to gene control. These two meanings seem to have evolved in concert with each other. The gene control instructions appear to help stabilize certain beneficial features of proteins and how they are made.

The discovery of duons has major implications for how scientists and physicians interpret a patient’s genome and will open new doors to the diagnosis and treatment of disease.

“The fact that the genetic code can simultaneously write two kinds of information means that many DNA changes that appear to alter protein sequences may actually cause disease by disrupting gene control programs or even both mechanisms simultaneously,” said Stamatoyannopoulos.

The wonder of DNA continues to amaze.

Related: Epigenetic Effects on DNA from Living Conditions in Childhood Persist Well Into Middle AgeDNA Passed to Descendants Changed by Your LifeDNA based Algorithmic Self-Assembly

Go Slow with Genetically Modified Food

My thoughts on Genetically Modified Organisms (GMO), specifically GM foods, basically boil down to:

  • messing with genes could create problems
  • we tend to (and especially those seeking to gain an advantage tend to – even if “we” overall wouldn’t the people in the position to take aggressive measures do) ignore risks until the problems are created (often huge costs at that point)
  • I think we should reduce risk and therefore make it hard to justify using GMO techniques
  • I agree occasionally we should do so, like it seems with oranges and bananas.
  • I agree the practice can be explained in a way that makes it seem like there is no (or nearly no) risk, I don’t trust we will always refrain from stepping into an area where there is a very bad result

Basically I would suggest being very cautious with GMO. I like science and technology but I think we often implement things poorly. I think we are not being cautious enough now, and should reduce the use of GMO to critical needs to society (patents on the practices need to be carefully studied and perhaps not permitted – the whole patent system is so broken now that it should be questioned at every turn).

Antibiotic misuse and massive overuse is an obvious example. We have doctors practicing completely unjustified misuse of antibiotics and harming society and we have factory farms massively overusing antibiotics causing society harm.

The way we casually use drugs is another example of our failure to sensibly manage risks, in my opinion. This of course is greatly pushed by those making money on getting us to use more drugs – drug companies and doctors paid by those companies. The right drugs are wonderful. But powerful drugs almost always have powerful side effects (at least in a significant number of people) and those risks are multiplied the more we take (due to interactions, weakness created by one being overwhelmed by the next etc.). We should be much more cautious but again we show evidence of failing to act cautiously which adds to my concern for using GMO.

I love antibiotics, but the way we are using them is endangering millions of lives (that is a bad thing). I don’t trust us to use science wisely and safely. We need to more consciously put barriers in place to provent us creating massively problems.

Related: Research on Wheat RustThe AvocadoOverfishing, another example of us failing to effectively cope with systemic consequences

Cell Aging and Limits Due to Telomeres

When cells divide the process fails to copy DNA all the way to the end. Telomeres are are the end of DNA strands, as essentially a buffer of material that won’t cause information to be lost when part of the telomere isn’t copied. As DNA is copied, as new cells are created, the length of telomeres at the end is reduced. Once the telomeres are gone the cell will no longer divide.

The 2009 Nobel Prize in Physiology or Medicine went to 3 scientists for discovering how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

There is some debate over the benefit of the mechanism of cells not dividing do to lack of telomere. This can prevent cancerous cells from replicating (once they replicate to the extent that the necessary telomere buffer is gone). It is also seen that as telomeres get shorter the cells become more likely to become cancerous.

Cancer also can stimulate the production of telomerase which can stop telomeres from getting shorter as cells divide and thus allow the cancer cells to keep dividing (thus producing more cancer cell and increasing the amount of cancerous cells). Using telomerase to allow health cells to avoid the limits of division is being researched.

Are Telomeres the Key to Aging and Cancer? (University of Utah)

An enzyme named telomerase adds bases to the ends of telomeres. In young cells, telomerase keeps telomeres from wearing down too much. But as cells divide repeatedly, there is not enough telomerase, so the telomeres grow shorter and the cells age.

Cells normally can divide only about 50 to 70 times, with telomeres getting progressively shorter until the cells become senescent, die or sustain genetic damage that can cause cancer.

shorter telomeres are associated with shorter lives. Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

While telomere shortening has been linked to the aging process, it is not yet known whether shorter telomeres are just a sign of aging – like gray hair – or actually contribute to aging.

Related: The Naked Mole Rat is the Only Known Cancerless AnimalWebcast of a T-cell Killing a Cancerous CellRNA interference webcast

Evolution Follows a Predictable Genetic Pattern

Far from random, evolution follows a predictable genetic pattern

The researchers carried out a survey of DNA sequences from 29 distantly related insect species, the largest sample of organisms yet examined for a single evolutionary trait. Fourteen of these species have evolved a nearly identical characteristic due to one external influence — they feed on plants that produce cardenolides, a class of steroid-like cardiotoxins that are a natural defense for plants such as milkweed and dogbane.

Though separated by 300 million years of evolution, these diverse insects — which include beetles, butterflies and aphids — experienced changes to a key protein called sodium-potassium adenosine triphosphatase, or the sodium-potassium pump, which regulates a cell’s crucial sodium-to-potassium ratio. The protein in these insects eventually evolved a resistance to cardenolides, which usually cripple the protein’s ability to “pump” potassium into cells and excess sodium out.

Andolfatto and his co-authors examined the sodium-potassium pump protein because of its well-known sensitivity to cardenolides. In order to function properly in a wide variety of physiological contexts, cells must be able to control levels of potassium and sodium. Situated on the cell membrane, the protein generates a desired potassium to sodium ratio by “pumping” three sodium atoms out of the cell for every two potassium atoms it brings in.

Cardenolides disrupt the exchange of potassium and sodium, essentially shutting down the protein, Andolfatto said. The human genome contains four copies of the pump protein, and it is a candidate gene for a number of human genetic disorders, including salt-sensitive hypertension and migraines. In addition, humans have long used low doses of cardenolides medicinally for purposes such as controlling heart arrhythmia and congestive heart failure.

Cool stuff. It makes sense to me which is nice (it is nice to get confirmation that I find what actually exists is sensible). When things that are true just seem crazy it is a bit disconcerting – like quantum mechanics. It is fun to read stuff that totally shakes up preconceived notions, but even then it is nice once I think understand it to find it sensible.

Related: All present-day Life on Earth Has A Single AncestorCambrian Explosion SongBacteriophages: The Most Common Life-Like Form on EarthMicrocosm by Carl Zimmer

Key Indicator for Malignant Melanoma Found

Skin cancer detection breakthrough

The researchers found that certain biochemical elements in the DNA of normal pigment-producing skin cells and benign mole cells are absent in melanoma cells. Loss of these methyl groups — known as 5-hmC — in skin cells serves as a key indicator for malignant melanoma. Loss corresponded to more-advanced stages of melanoma as well as clinical outcome.

Strikingly, researchers were able to reverse melanoma growth in preclinical studies. When the researchers introduced enzymes responsible for 5-hmC formation to melanoma cells lacking the biochemical element, they saw that the cells stopped growing.

“It is difficult to repair the mutations in the actual DNA sequence that are believed to cause cancer,” said Christine Lian, a physician-scientist in the Department of Pathology at BWH and one of the lead authors. “So having discovered that we can reverse tumor cell growth by potentially repairing a biochemical defect that exists — not within the sequence but just outside of it on the DNA structure — provides a promising new melanoma treatment approach for the medical community to explore.”

Because cancer is traditionally regarded as a genetic disease involving permanent defects that directly affect the DNA sequence, this new finding of a potentially reversible abnormality that surrounds the DNA (thus termed “epigenetic”) is a hot topic in cancer research, according to the researchers.

In the United States, melanoma is the fifth most common type of new cancer diagnosis in men and the seventh most common type in women. The National Cancer Institute estimates that in 2012 there will be 76,250 new cases and 9,180 deaths in the United States owing to melanoma.

Thankfully scientists keep making great progress in understanding and finding potential clues to treating cancer. And big gains have been made in treating some cancers over the last few decades. But the research successes remain difficult to turn into effective solutions in treating patients.

I am thankful we have so many scientists doing good work in this difficult and important area (cancer).

Related: Webcast of a T-cell Killing a Cancerous CellNanoparticles With Scorpion Venom Slow Cancer SpreadDNA Passed to Descendants Changed by Your LifeResearchers Find Switch That Allows Cancer Cells to Spread

Changing Life as We Know It

Update: Independent researchers find no evidence for arsenic life in Mono Lake

NASA has made a discovery that changes our understanding of the very makeup of life itself on earth. I think my favorite scientific discipline name is astrobiology. NASA pursues a great deal of this research not just out in space but also looking at earth based life. Their astrobiology research has changed the fundamental knowledge about what comprises all known life on Earth.

photo of Felisa Wolfe-Simon

Felisa Wolfe-Simon processing mud from Mono Lake to inoculate media to grow microbes on arsenic.

Carbon, hydrogen, nitrogen, oxygen, phosphorus and sulfur are the six basic building blocks of all known forms of life on Earth. Phosphorus is part of the chemical backbone of DNA and RNA, the structures that carry genetic instructions for life, and is considered an essential element for all living cells.

Phosphorus is a central component of the energy-carrying molecule in all cells (adenosine triphosphate) and also the phospholipids that form all cell membranes. Arsenic, which is chemically similar to phosphorus, is poisonous for most life on Earth. Arsenic disrupts metabolic pathways because chemically it behaves similarly to phosphate.

Researchers conducting tests in the harsh, but beautiful (see photo), environment of Mono Lake in California have discovered the first known microorganism on Earth able to thrive and reproduce using the toxic chemical arsenic. The microorganism substitutes arsenic for phosphorus in its cell components.

“The definition of life has just expanded,” said Ed Weiler, NASA’s associate administrator for the Science Mission Directorate. “As we pursue our efforts to seek signs of life in the solar system, we have to think more broadly, more diversely and consider life as we do not know it.” This finding of an alternative biochemistry makeup will alter biology textbooks and expand the scope of the search for life beyond Earth.

In science such huge breakthroughs are not just excepted without debate, however, which is wise.

Thriving on Arsenic:

In other words, every experiment Wolfe-Simon performed pointed to the same conclusion: GFAJ-1 can substitute arsenic for phosphorus in its DNA. “I really have no idea what another explanation would be,” Wolfe-Simon says.

But Steven Benner, a distinguished fellow at the Foundation for Applied Molecular Evolution in Gainesville, FL, remains skeptical. If you “replace all the phosphates by arsenates,” in the backbone of DNA, he says, “every bond in that chain is going to hydrolyze [react with water and fall apart] with a half-life on the order of minutes, say 10 minutes.” So “if there is an arsenate equivalent of DNA in that bug, it has to be seriously stabilized” by some as-yet-unknown mechanism.

It is sure a great story if it is true though. Other scientists will examine more data and confirm or disprove the claims.

“We know that some microbes can breathe arsenic, but what we’ve found is a microbe doing something new — building parts of itself out of arsenic,” said Felisa Wolfe-Simon, a NASA Astrobiology Research Fellow in residence at the U.S. Geological Survey in Menlo Park, Calif., and the research team’s lead scientist. “If something here on Earth can do something so unexpected, what else can life do that we haven’t seen yet?”
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Variation in Human DNA

Variation on the order of thousands to hundreds of thousands of DNA’s smallest pieces – large swaths varying in length or location or even showing up in reverse order – appeared 4,205 times in a comparison of DNA from just four people.

Those structural differences popped into clear view through computer analysis of more than 500 linear feet of DNA molecules analyzed by the powerful genome mapping system developed over nearly two decades by David C. Schwartz, professor of chemistry and genetics at UW-Madison.

“We probably have the most comprehensive view of the human genome ever,” Schwartz says. “And the variation we’re seeing in the human genome is something we’ve known was there and important for many years, but we haven’t been able to fully study it.”

To get a better picture of those structural variations, Schwartz and his team developed the Optical Mapping System, a wholly new type of genome analysis that directly examines millions of individual DNA molecules.

“Our newer genome analysis systems, if commercialized, promise genome analysis in one hour, at under $1,000,” Schwartz says. “And we require that high speed and low cost to power the new field of personal genomics.”

Read full press release

Related: New Understanding of Human DNAOpossum Genome Shows ‘Junk’ DNA is Not JunkBacteria Can Transfer Genes to Other BacteriaScientists crack 40-year-old DNA puzzle

Sumatran Tiger and Cubs Filmed by Remote Wildlife Monitoring Cameras

Video cameras installed in the Sumatran jungle in Indonesia have captured close-up footage of a tiger and two cubs. This is the first time that the World Wildlife Fund has recorded evidence of tiger breeding in central Sumatra in what should be prime tiger habitat.

The Sumatran Tiger is the smallest of all surviving tiger subspecies. Male Sumatran tigers average 204 cm (6 feet, 8 inches) in length from head to tail and weigh about 136 kg (300 lb).

Analysis of DNA is consistent with the hypothesis that the Sumatran Tigers have been isolated after a rise in sea level at the Pleistocene to Holocene border (about 12,000-6,000 years ago) from other tiger populations. The Sumatran Tiger is genetically isolated from all living mainland tigers.

Wouldn’t it be nice to see the photos those tigers could take with the awesome cat cam?

Related: Bukit Tiga Puluh National ParkUsing Cameras Monitoring To Aid Conservation EffortsRare Saharan Cheetahs PhotographedJaguars Back in the Southwest USA

Microcosm by Carl Zimmer

cover of Microcosm by Carl Zimmer

Microcosm: E. Coli and the New Science of Life by Carl Zimmer is an excellent book. It is full of fascinating information and as usual Carl Zimmer’s writing is engaging and makes complex topics clear.

E-coli keep the level of oxygen low in the gut making the resident microbes comfortable. At any time a person will have as many as 30 strains of E. coli in their gut and it is very rare for someone ever to be free of E. coli. [page 53]

In 1943, Luria and Delbruck published the results that won them the 1969 Nobel Prize in Physiology or Medicine in which they showed that bacteria and viruses pass down their traits using genes (though it took quite some time for the scientific community at large to accept this). [page 70]

during a crisis E coli’s mutation rates could soar a hundred – or even a thousandfold… Normally, natural selection favors low mutation rates, since most mutations are harmful. But in times of stress extra mutations may raise the odds that organisms will hit on a way out of their crisis… [alternatively, perhaps] In times of stress, E coli. may not be able to afford the luxury of accurate DNA repair. Instead, it turns to the cheaper lo-fi polymerases. While they may do a sloppier job, E coli. comes out ahead [page 106]
Hybridization is not the only way foreign DNA got into our cells. Some 3 billion years ago our single-celled ancestors engulfed oxygen-breathing bacteria, which became the mitochondria on which we depend. And, like E. coli, our genomes have taken in virus upon virus. Scientists have identified more than 98,000 viruses in the human genome, along with our mutant vestiges of 150,00 others… If we were to strip out all our transgenic DNA, we would become extinct.

I highly recommend Microcosm, just as I highly recommend Parasite Rex, by Carl Zimmer.

Related: Bacteriophages: The Most Common Life-Like Form on EarthForeign Cells Outnumber Human Cells in Our BodiesAmazing Designs of LifeAmazing Science: RetrovirusesOne Species’ Genome Discovered Inside Another’s

Science Explained: RNA Interference

Explained: RNA interference

Every high school biology student learns the basics of how genes are expressed: DNA, the cell’s master information keeper, is copied into messenger RNA, which carries protein-building instructions to the ribosome, the part of the cell where proteins are assembled.

But it turns out the picture is far more complicated than that. In recent years, biologists have discovered a myriad of other molecules that fine-tune this process, including several types of RNA (ribonucleic acid). Through a naturally occurring phenomenon known as RNA interference, short strands of RNA can selectively intercept and destroy messenger RNA before it delivers its instructions.

Double-stranded RNA molecules called siRNA (short interfering RNA) bind to complementary messenger RNA, then enlist the help of proteins, the RNA-induced silencing complex. Those proteins cleave the chemical bonds holding messenger RNA together and prevent it from delivering its protein-building instructions.

This article from MIT is one, of many, showing MIT’s commitment to science education of the public. Good job, MIT.

Related: Antigen Shift in Influenza VirusesPosts explaining scientific principles and conceptsDNA Passed to Descendants Changed by Your LifeWhy Does Hair Turn Grey as We Age?Amazing Science: Retroviruses

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