Archive for September 17th, 2011

September 17, 2011

Are genes our destiny? ‘Hidden’ code in DNA evolves more rapidly than genetic code, scientists discover

Molecular biologists have known for some time that the genetic code residing in an organism’s DNA is not the only determinant of the organism’s characteristics (its “phenotype“). Identical twin animals and humans, and clones of plants, have the same DNA as their counterparts – yet they are not identical to each other. Various factors can alter how the same DNA is expressed in corresponding cells of twins and clones. The study of these factors makes up the science of epigenetics.

One of the most important epigenetic mechanisms is DNA methylation, which is a chemical modification to individual DNA nucleotides. It is usually the addition of a methyl group to a cytosine base that is adjacent to a guanine base. In humans up to 90% of cytosine-guanine pairs may be methylated. Methylation usually has the effect of silencing genes if it occurs in a gene’s promoter region.

Methylation patterns can be inherited in successive generations of a plant or animal. However, not too surprisingly, small changes of the pattern can occur, since the normal DNA copying process doesn’t automatically reproduce the methylation. Nevertheless, once a mutation of the pattern has occurred in an egg or sperm cell, it can be passed on to later generations. An obvious question is about how the rate of such epigenetic mutations compares with that of mutations in the DNA itself.

New research has answered that question for Arabidopsis thaliana, a form of cress that is a popular model organism for plant biologists. As it happens, mutations of methylation sites occur a whole lot more often than DNA mutations – about 5 orders of magnitude more often.

Are genes our destiny? ‘Hidden’ code in DNA evolves more rapidly than genetic code, scientists discover

The researchers discovered that as many as a few thousand methylation sites on the plants’ DNA were altered each generation. Although this represents a small proportion of the potentially six million methylation sites estimated to exist on Arabidopsis DNA, it dwarfs the rate of spontaneous change seen at the DNA sequence level by about five orders of magnitude.

This suggests that the epigenetic code of plants – and other organisms, by extension – is far more fluid than their genetic code.

Even more surprising was the extent to which some of these changes turned genes on or off. A number of plant genes that underwent heritable changes in methylation also experienced substantial alterations in their expression – the process by which genes control cellular function through protein production.

Further reading:

Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants

September 17, 2011

Surprising Cells Rein In Killer Flu

Potentially lethal strains of influenza wreak havoc indirectly – by overstimulating the immune system to produce a cytokine storm. Such cytokine storms arise from a positive feedback loop in the immune system that gets out of control. Excessive levels of cytokine signaling molecules are produced, causing immune cells such as macrophages and natural killer cells to swarm into the site of infection (the lungs in the case of influenza), producing even more cytokines, and so on.

The immune system has mechanisms that normally control this process, but somehow certain strains of influenza – such as the Spanish Influenza of 1918 – apparently interfere with the controls. Now a way has been found that seems to quiet the storm, and it involves cells that aren’t even part of the immune system.

Sphingosine-1-phosphate, a signaling molecule that is active in some immune system cells, is triggered by a cell surface receptor, S1P1. It was found that a chemical that binds this receptor (an “agonist“) could prevent cytokine storms in mice infected with influenza. The S1P1 receptor exists on the surface of immune system lymphocytes – but also on the surface of endothelial cells occurring on the inner lining of lymphatic and blood vessels in the lung. Surprisingly enough, it seems that binding S1P1 on the endothelial cells is what calms the cytokine storm, since the S1P1 agonist was effective even in mice that lacked lymphocytes.

Surprising Cells Rein In Killer Flu – ScienceNOW

When the researchers went looking for the cells in the lungs that carry the S1P1 receptor, they found that it occurs on endothelial cells, which line lymphatic and blood vessels, and on the white blood cells known as lymphocytes. That was unexpected because “they are not the cells that are infected by the virus,” Oldstone says. To determine which of these two cell types controls the cytokine surge, the researchers tested the S1P1 receptor activator in mice that lack lymphocytes. The compound also prevented the storms in these animals, suggesting that endothelial cells, not lymphocytes, orchestrate cytokine release.

For mice at least, the S1P1 receptor can be a lifesaver. After infecting the rodents with a flu virus isolated from a patient who fell ill during the 2009 swine flu outbreak, Rosen and colleagues dosed some of the animals with a compound that stimulates the receptor. The death rate was 80% in untreated animals buy only 20% in the mice that received the molecule.

Further reading:

Cytokine storms

Blocking Flu Death

Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection

September 17, 2011

Brainy molluscs evolved nervous systems four times

External appearance, it turns out, is not a good way to identify relationships between species, especially more distant relationships. And even internal anatomical structure isn’t so good either. Studies of genomes at the molecular level are more reliable. In the latest example, it’s been found that snails and octopuses do not seem to be as closely related as previously believed, even though the two cephalopods both have relatively complex nervous systems (compared to other molluscs such as clams).

Examination of the genomes can also provide estimates of how much time elapsed since different species shared a common ancestor. Based on this, it appears that the nervous systems of snails and octopuses developed their complexity independently, as probably happened also in two other less familiar types of mollusc.

Brainy molluscs evolved nervous systems four times – New Scientist

Slimy and often sluggish they may be, but some molluscs deserve credit for their brains – which, it now appears, they managed to evolve independently, four times.

The mollusc family includes the most intelligent invertebrates on the planet: octopuses, squid and cuttlefish. Now, the latest and most sophisticated genetic analysis of their evolutionary history overturns our previous understanding of how they got so brainy.

The new findings expand a growing body of evidence that in very different groups of animals – molluscs and mammals, for instance – central nervous systems evolved not once, but several times, in parallel.

Further reading:

Mollusks evolved brains on four different occasions

Phylogenomics reveals deep molluscan relationships

September 17, 2011

Clues emerge to explain first successful HIV vaccine trial

HIV, the AIDS-causing virus, is a master of eluding the body’s immune system – in part because it targets cells of the immune system itself as part of its reproductive strategy. This makes development of vaccines to protect against HIV especially difficult, because vaccines require a functioning immune system in order to work. If HIV escapes early immune system defenses, later defenses may fail.

The first modestly encouraging clinical trial of an anti-HIV vaccine was announced two years ago. Frustratingly, however, it was not clear how the vaccine involved actually worked.

Scientists are still studying blood samples from trial participants to search for differences that might explain why the vaccine worked for some but not for others. So far two antibodies have been identified that target different HIV antigens – one antibody that is associated with more successful results, and the other with less successful ones. These are the first clues ever found that seem to point towards a successful HIV vaccine mechanism.

Clues emerge to explain first successful HIV vaccine trial – Nature News

Barton Haynes, the director of the Duke Human Vaccine Institute in Durham, North Carolina, who coordinated the follow-up study, said at a press conference that the results will generate hypotheses for further study. “What we now have are clues as to why it might have worked. That’s something we haven’t had over the past 30 years. That’s very important for the field.”

Researchers are already planning to test whether antibodies like those found in trial participants have the same effect in primates infected with a virus related to HIV. These experiments will determine whether these immune responses are responsible for the vaccine’s success or failure in particular people or merely linked to other underlying factors.

Further reading:

Why the Thai HIV Vax Trial Worked

September 17, 2011

Particle physics: The dark at the end of the tunnel?

Dark matter is certainly nothing if not elusive. If dark matter does not exist in some form or other, there are serious problems with much of what astrophysicists think they know about the evolution of the universe. There are numerous types of astrophysical observations which can be explained by the existence of dark matter. But these explanations are contingent upon both the existence of dark matter in the form of some sort of as yet unknown particles (“WIMPs“) and also the correctness of accepted fundamental laws of physics – such as Newtonian gravity. If dark matter doesn’t exist, then the fundamental laws are also called into question.

Particle physics: The dark at the end of the tunnel? – The Economist

To identify dark matter, experiments like DAMA, CRESST and CoGeNT look for weak-force-mediated collisions between atoms on Earth and WIMPs in the dark-matter halo of the Earth’s home galaxy, the Milky Way. Such collisions should cause individual atomic nuclei to recoil, and with the right apparatus such recoils can be observed. To screen out the confounding effects of cosmic rays, though, such experiments are best located underground.

read more »

September 17, 2011

Researchers discover a switch that controls stem cell pluripotency

Stem cell scientists are continuing to turn up new information on how embryonic (and other) stem cells work. Embryonic stem cells are pluripotent, meaning they can transform into any other cell type. But what determines when and how this happens? The latest research reveals one particular process, probably out of many.

The FOXP1 gene codes for a transcription factor that regulates the expression of other genes important in embryonic development. As it turns out, very slightly different proteins can be produced from FOXP1, depending on a process, alternative splicing, that affects the derived messenger RNA. In one form of the final transcription factor, genes that maintain pluripotency are expressed: OCT4, NANOG, NR5A2, and GDF3. But in the alternative form, genes are expressed that cause the cell to differentiate into a non-pluripotent cell. The question remains as to what causes splicing to take one path or the other.

Researchers discover a switch that controls stem cell pluripotency

Scientists have found a control switch that regulates stem cell “pluripotency,” the capacity of stem cells to develop into any type of cell in the human body. The discovery reveals that pluripotency is regulated by a single event in a process called alternative splicing.

Alternative splicing allows one gene to generate many different genetic messages and protein products. The researchers found that in genetic messages of a gene called FOXP1, the switch was active in embryonic stem cells but silent in “adult” cells—those that had become the specialized cells that comprise organs and perform functions.

Further reading:

An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming