[Centraal] Evolutie in het nieuws

quote:

HIV Is Evolving To Evade Human Immune Responses

ScienceDaily (Feb. 28, 2009) — HIV is evolving rapidly to escape the human immune system, an international study led by Oxford University has shown. The findings, published in Nature, demonstrate the challenge involved in developing a vaccine for HIV that keeps pace with the changing nature of the virus.

'The extent of the global HIV epidemic gives us a unique opportunity to examine in detail the evolutionary struggle being played out in front of us between an important virus and humans,’ says lead researcher Professor Philip Goulder of the Peter Medawar Building for Pathogen Research at Oxford University.

‘Even in the short time that HIV has been in the human population, it is doing an effective job of evading our best efforts at natural immune control of the virus. This is high-speed evolution that we’re seeing in the space of just a couple of decades.’

The study better describes HIV's ability to adapt by spelling out at least 14 different "escape mutations" that help keep the virus alive after it interacts genetically with immunity molecules that normally attack HIV.

"Key genetic regions of HIV introduced into individuals of different ancestry in different places have been evolving to a greater or lesser degree according to inherited factors controlling immune response," said Richard Kaslow, M.D., a professor in the UAB School of Public Health and a co-author of the study. "If HIV adapts differently in genetically distinct hosts, the challenge ahead in vaccine design is formidable," he said.

HIV has already killed 25 million people, and an estimated 33 million are currently infected. However, HIV does not kill all people at the same rate. On average, an adult with HIV will survive for ten years without anti-HIV drugs before developing AIDS. But some people will progress to AIDS within 12 months while others can make effective immune responses to the virus and survive without any anti-HIV therapy for over 20 years.

Genes encoding a key set of molecules in the human immune system called the human leucocyte antigens (HLA) are critically important. HLA determine the progress of many infectious diseases including HIV, and enable the recognition and killing of HIV-infected cells. Humans differ from each other in the exact HLA genes they have, and small differences can make the difference in how long it takes to progress to AIDS.

The research team set out to determine whether HIV is adapting to human immune responses. They looked at HIV genetic sequences in different countries around the world, including the UK, South Africa, Botswana, Australia, Canada, and Japan, wanting to see whether the HIV sequences could be related to the different HLA genes present in the different populations.

The collaboration between Oxford University, the Ragon Institute at Massachusetts General Hospital, Kumamoto University in Japan, the Royal Perth Hospital and Murdoch University in Australia and others analysed the genetic sequences of the HIV virus and human leucocyte antigen (HLA) genes in over 2,800 people.

Mutations that allow HIV to get round immune responses directed by a particular HLA gene were found more frequently in populations with a high prevalence of that HLA gene. This is strong evidence for HIV adaptation to the human immune system at the level of populations.

‘Where a favourable HLA gene is present at high levels in a given population, we see high levels of the mutations that enable HIV to resist this particular gene effect,’ says author Professor Rodney Phillips, co-director of the James Martin Institute for Emerging Infections at Oxford University. ‘The virus is outrunning human variation, you might say.’

‘The temptation is to see this as bad news, that these results mean the virus is winning the battle,’ says Professor Goulder. ‘That’s not necessarily the case. It could equally be that as the virus changes, different immune responses come into play and are actually more effective.’

The results are important because it is our most effective immune responses that vaccines against HIV would try and boost to a level that would protect against the virus.

‘The implication is that once we have found an effective vaccine, it would need to be changed on a frequent basis to catch up with the evolving virus, much like we do today with the flu vaccine,’ explains Professor Goulder.

‘In this anniversary year of Darwin’s birth, we are accustomed to think of evolution happening over thousands, tens of thousands and even millions of years,’ says Professor Goulder. ‘But we are seeing changes in HIV, and our immune response to the virus, in just a couple of decades.’

The work was funded by a number of organisations including the Wellcome Trust, the Medical Research Council, the US National Institutes of Health, and Oxford’s James Martin 21st Century School.

quote:

McEvoy, B.P. et al. (2009) Geographical structure and differential natural selection amongst North European populations. Genome Research, in press.


Population structure can provide novel insight into the human past and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, UK, Netherlands, Denmark, Sweden, Finland, Australia and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and -American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogenous region. There is evidence from FST based analysis of genic and non-genic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to HLA-G gene on chromosome 6. Evidence of the sweep extends over 8Mb/3.5cM region. Overall the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it and their implications in both explaining disease prevalence and mapping these genes by association

quote:

Gallet, R. (2009) Ecological Conditions Affect Evolutionary Trajectory in a Predator-Prey system. Evolution, 63, 641 - 651.

The arms race of adaptation and counter adaptation in predator–prey interactions is a fascinating evolutionary dynamic with many consequences, including local adaptation and the promotion or maintenance of diversity. Although such antagonistic coevolution is suspected to be widespread in nature, experimental documentation of the process remains scant, and we have little understanding of the impact of ecological conditions. Here, we present evidence of predator–prey coevolution in a long-term experiment involving the predatory bacterium Bdellovibrio bacteriovorus and the prey Pseudomonas fluorescens, which has three morphs (SM, FS, and WS). Depending on experimentally applied disturbance regimes, the predator–prey system followed two distinct evolutionary trajectories, where the prey evolved to be either super-resistant to predation (SM morph) without counter-adaptation by the predator, or moderately resistant (FS morph), specialized to and coevolving with the predator. Although predation-resistant FS morphs suffer a cost of resistance, the evolution of extreme resistance to predation by the SM morph was apparently unconstrained by other traits (carrying capacity, growth rate). Thus we demonstrate empirically that ecological conditions can shape the evolutionary trajectory of a predator–prey system.

Conclusion
From one single ancestral strain, we observed two distinct evolutionary outcomes depending on the experimental ecological treatments. When disturbances were frequent or moderate, the FS morph usually went to fixation. When disturbances were relatively infrequent and not intense, it was possible for the SM morph to go to fixation. Antagonistic coevolution with specialization between predator and prey was observed where the FS morph went to fixation and not where the SM morph went to fixation. The predator failed to counter-adapt to the form of the SM morph that emerged. Only where the disturbance regime favored the SM morph did it persist long enough to evolve extreme resistance to predation. This suggests that there may be several alternative evolutionary or genetic pathways that a prey or host may follow to develop resistance to predation or parasitism. These alternative pathways seem to be favored by different disturbance regimes. In other words, in our experiment, disturbance seems to have driven predator–prey populations toward different features on their evolutionary landscape, with either the evolution of prey resistance (SM) or an antagonistic predator–prey coevolution (FS). This suggests that microorganisms evolve on much more complex and changing adaptive landscapes than previously thought, warranting the exploration of more than one culturing regime (in contrast to most experimental evolution designs).

Our results also provide information about the adaptive capacities of B. bacteriovorus. Thus far, this predatory bacterium was known as a generalist preying on various Gram− bacteria strain. Ours is the first report of specialization to a specific prey by B. bacteriovorus; further, we showed that the predation efficiency of B. bacteriovorus increased only on certain prey morphs. This result might be viewed as surprising and intriguing, given B. bacteriovorus's profile as a generalist. Our results also contradict the notion that resistance to B. bacteriovorus is rare. Unfortunately, nothing is known about the mechanistic details of this prey–predator system, so we do not know if resistance to predation by B. bacteriovorus in P. fluorescens is the result of a reduced ability to enter the periplasm of the prey or less accessible cytoplasm, among other possibilities. A better understanding of the mechanisms involved in the predator–prey interaction between B. bacteriovorus and P. fluorescens might allow us to identify the cause of high resistance to predation by the SM morph and the constraints acting on resistance to predation in the FS morph.

This should also inspire caution about the use of B. bacteriovorus as an environmental prophylactic or as an alternative to antibiotic therapy (Sockett and Lambert 2004). Many diseases have evolved resistance to antibiotics (e.g., tuberculosis; Abdel Aziz and Wright 2005). "Living antibiotics" must also be considered carefully regarding the way their efficiency might be shaped by evolution. Successful long-term control of diseases, pests, and invasive species will require a better understanding of coevolutionary dynamics in an ecological context.

quote:

Cretaceous Octopus With Ink And Suckers -- The World's Least Likely Fossils?

ScienceDaily (Mar. 18, 2009) — New finds of 95 million year old fossils reveal much earlier origins of modern octopuses. These are among the rarest and unlikeliest of fossils. The chances of an octopus corpse surviving long enough to be fossilized are so small that prior to this discovery only a single fossil species was known, and from fewer specimens than octopuses have legs.

Even if you have never encountered an octopus in the flesh, the eight arms, suckers, and sack-like body are almost as familiar a body-plan as the four legs, tail and head of cats and dogs. Unlike our vertebrate cousins, however, octopuses don't have a well-developed skeleton. And while this famously allows them to squeeze into spaces that a more robust animal could not, it does create problems for scientists interested in evolutionary history. When did octopuses acquire their characteristic body-plan, for example? Nobody really knows, because fossil octopuses are rarer than, well, pretty much any very rare thing you care to mention.

The body of an octopus is composed almost entirely of muscle and skin, and when an octopus dies, it quickly decays and liquefies into a slimy blob. After just a few days there will be nothing left at all. And that assumes that the fresh carcass is not consumed almost immediately by hungry scavengers. The result is that preservation of an octopus as a fossil is about as unlikely as finding a fossil sneeze, and none of the 200-300 species of octopus known today has ever been found in fossilized form. Until now, that is.

Palaeontologists have just identified three new species of fossil octopus discovered in Cretaceous rocks in Lebanon. The five specimens, described in the latest issue of the journal Palaeontology, are 95 million years old but, astonishingly, preserve the octopuses' eight arms with traces of muscles and those characteristic rows of suckers. Even traces of the ink and internal gills are present in some specimens. '

"These are sensational fossils, extraordinarily well preserved," says Dirk Fuchs of the Freie University Berlin, lead author of the report. But what surprised the scientists most was how similar the specimens are to modern octopus: "these things are 95 million years old, yet one of the fossils is almost indistinguishable from living species." This provides important evolutionary information. "The more primitive relatives of octopuses had fleshy fins along their bodies. The new fossils are so well preserved that they show, like living octopus, that they didn't have these structures." This pushes back the origins of modern octopus by tens of millions of years, and while this is scientifically significant, perhaps the most remarkable thing about these fossils is that they exist at all.

Publicatie
Fuchs et al. New Octopods (Cephalopoda: Coleoidea) from the Late Cretaceous (Upper Cenomanian) of Hakel and Hadjoula, Lebanon. Palaeontology, 2009; 52 (1): 65

quote:

Somel, M. et al. (2009) Transcriptional neoteny in the human brain. PNAS, advance online.

In development, timing is of the utmost importance, and the timing of developmental processes often changes as organisms evolve. In human evolution, developmental retardation, or neoteny, has been proposed as a possible mechanism that contributed to the rise of many human-specific features, including an increase in brain size and the emergence of human-specific cognitive traits. We analyzed mRNA expression in the prefrontal cortex of humans, chimpanzees, and rhesus macaques to determine whether human-specific neotenic changes are present at the gene expression level. We show that the brain transcriptome is dramatically remodeled during postnatal development and that developmental changes in the human brain are indeed delayed relative to other primates. This delay is not uniform across the human transcriptome but affects a specific subset of genes that play a potential role in neural development.

quote:

Op dinsdag 24 maart 2009 15:39 schreef barthol het volgende:

[..]

Interessant artikel. Gould suggereerde indertijd ook al die neotenie.

quote:

Gunz, P. et al. (2009) Early modern human diversity suggests subdivided population structure and a complex out-of-Africa scenario. PNAS, advance online

The interpretation of genetic evidence regarding modern human origins depends, among other things, on assessments of the structure and the variation of ancient populations. Because we lack genetic data from the time when the first anatomically modern humans appeared, between 200,000 and 60,000 years ago, instead we exploit the phenotype of neurocranial geometry to compare the variation in early modern human fossils with that in other groups of fossil Homo and recent modern humans. Variation is assessed as the mean-squared Procrustes distance from the group average shape in a representation based on several hundred neurocranial landmarks and semilandmarks. We find that the early modern group has more shape variation than any other group in our sample, which covers 1.8 million years, and that they are morphologically similar to recent modern humans of diverse geographically dispersed populations but not to archaic groups. Of the currently competing models of modern human origins, some are inconsistent with these findings. Rather than a single out-of-Africa dispersal scenario, we suggest that early modern humans were already divided into different populations in Pleistocene Africa, after which there followed a complex migration pattern. Our conclusions bear implications for the inference of ancient human demography from genetic models and emphasize the importance of focusing research on those early modern humans, in particular, in Africa

quote:

Food Choices Evolve Through Information Overload

ScienceDaily (Mar. 30, 2009) — Ever been so overwhelmed by a huge restaurant menu that you end up choosing an old favourite instead of trying something new?

Psychologists have long since thought that information overload leads to people repeatedly choosing what they know. Now, new research has shown that the same concept applies equally to hundreds of animal species, too.

Researchers from the University of Leeds have used computer modelling to examine the evolution of specialisation, casting light on why some animal species have evolved to eat one particular type of food. For example some aphids choose to eat garden roses, but not other plants which would offer similar nutritional values.

"This is a major leap forward in our understanding of the way in which animals interact with their environment," says lead researcher Dr Colin Tosh from the University's Faculty of Biological Sciences. "Our computer models show the way in which neural networks operate in different environments. They have made it possible for us to see how different species make decisions, based on what's happening – or in this case, which foods are available - around them."

Despite the prevalence of specialisation in the animal kingdom, very little is known about why it occurs. The work conducted at Leeds has provided strong evidence in support of the 'neural limitations' hypothesis put forward by academics in the 1990s. This hypothesis, derived from human psychology, is based on the concept of information overload.

"There are several hypotheses to explain specialisation: one suggests that animals adapt to eat certain foods and this prevents them from eating other types of food," says Dr Tosh.

"For example, cows have evolved flat teeth which allow them to chew grass but they are unable to efficiently process meat. However, the problem with these hypotheses is that they don't apply across the board. Some species – such as many plant eating insects – have evolved to specialise even though there are many other available foods they could eat perfectly well."

This is the first study to provide a realistic representation of neural information processing in animals and how these interact with their environment. The research team believe that it could also have major implications for predicting the effects of environmental change.

"A good example of a struggling specialist is the giant panda, which relies on high mountain bamboo," says Dr Tosh. "In understanding how neural processes work, we may be able to gain an insight into how future environmental conditions – such as the dying out of particular types of plants - may affect a range of different animal species that utilise them for food."

quote:

New Theory On Largest Known Mass Extinction In Earth's History

ScienceDaily (Mar. 31, 2009) — The largest mass extinction in the history of the earth could have been triggered off by giant salt lakes, whose emissions of halogenated gases changed the atmospheric composition so dramatically that vegetation was irretrievably damaged.

At least that is what an international team of scientists has reported in the most recent edition of the Proceedings of the Russian Academy of Sciences (Dokladi Earth Sciences). At the Permian/Triassic boundary, 250 million years ago, about 90 percent of the animal and plant species ashore became extinct. Previously it was thought that volcanic eruptions, the impacts of asteroids, or methane hydrate were instigating causes.

The new theory is based on a comparison with today's biochemical and atmospheric chemical processes. "Our calculations show that airborne pollutants from giant salt lakes like the Zechstein Sea must have had catastrophic effects at that time", states co-author Dr. Ludwig Weißflog from the Helmholtz-Center for Environmental Research (UFZ). Forecasts predict an increase in the surface areas of deserts and salt lakes due to climate change. That is why the researchers expect that the effects of these halogenated gases will equally increase.

The team of researchers from Russia, Austria, South Africa and Germany investigated whether a process that has been taking place since primordial times on earth could have led to global mass extinctions, particularly at the end of the Permian. The starting point for this theory was their discovery in the south of Russia and South Africa that microbial processes in present-day salt lakes naturally produce and emit highly volatile halocarbons such as chloroform, trichloroethene, and tetrachloroethene.

They transcribed these findings to the Zechstein Sea, which about 250 million years ago in the Permian Age, was situated about where present day Central Europe is. The Zechstein Sea with a total surface area of around 600.000 km2 was almost as large as France is today. The hyper saline flat sea at that time was exposed to a predominantly dry continental desert climate and intensive solar radiation – like today’s salt seas. "Consequently, we assume that the climatic, geo-chemical and microbial conditions in the area of the Zechstein Sea were comparable with those of the present day salt seas that we investigated," Weißflog said.

In their current publication the authors explain the similarities between the complex processes of the CO2-cycle in the Permian Age as well as between global warming from that time and at present. Based on comparable calculations from halogenated gas emissions in the atmosphere from present-day salt seas in the south of Russia, the scientists calculated that from the Zechstein Sea alone an annual VHC emissions rate of at least 1.3 million tonnes of trichloroethene, 1.3 million tonnes of tetrachloroethene, 1.1 million tonnes of chloroform as well as 0.050 million tonnes of methyl chloroform can be assumed. By comparison, the annual global industrial emissions of trichloroethene and tetrachloroethene amount to only about 20 percent of that respectively, and only about 5 percent of the chloroform from the emissions calculated for the Zechstein Sea by the scientists. Incidentally, the industrial production of methyl chloroform, which depletes the ozone layer, has been banned since 1987 by regulation of the Montreal Protocol.

"Using steppe plant species we were able to prove that halogenated gases contribute to speeding up desertification: The combination of stress induced by dryness and the simultaneous chemical stressor „halogenated hydrocarbons“ disproportionately damages and destabilize the plants and speeds up the process of erosion," Dr. Karsten Kotte from the University of Heidelberg explained.

Based on both of these findings the researchers were able to form their new hypothesis: At the end of the Permian Age the emissions of halogenated gases from the Zechstein Sea and other salt seas were responsible in a complex chain of events for the world's largest mass extinction in the history of the earth, in which about 90 percent of the animal and plant species of that time became extinct.

According to the forecast from the International Panel on Climate Change (IPCC), increasing temperatures and aridity due to climate change will also speed up desertification, increasing with it the number and surface area of salt seas, salt lagoons and salt marshlands. Moreover, this will then lead to an increase in naturally formed halogenated gases. The phytotoxic effects of these substances become intensified in conjunction with other atmospheric pollutants and at the same time increasing dryness and exponentiate the eco-toxicological consequences of climate change.

The new theory could be like a jigsaw piece that contributes to solving the puzzle of the largest mass extinction in the history of the earth. "The question as to whether the halogenated gases from the giant salt lakes alone were responsible for it or whether it was a combination of various factors with volcanic eruptions, the impact of asteroids, or methane hydrate equally playing their role still remains unanswered," Ludwig Weißflog said. What is fact however is that the effects of salt seas were previously underestimated.

In their publication the researchers working with Dr. Ludwig Weißflog from the UFZ and Dr. Karsten Kotte from the University of Heidelberg want to showed that recent salt lakes and salt deserts of south-east Europe, Middle Asia, Australia, Africa, America can not only influence the regional but also the global climate. The new findings on the effects of these halogenated gases are important for revising climate models, which form the basis for climate forecasts.

quote:

Evolution-proof Insecticides May Stall Malaria Forever

ScienceDaily (Apr. 7, 2009) — Killing just the older mosquitoes would be a more sustainable way of controlling malaria, according to entomologists who add that the approach may lead to evolution-proof insecticides that never become obsolete.

Each year malaria -- spread through mosquito bites -- kills about a million people, but many of the chemicals used to kill the insects become ineffective. Repeated exposure to an insecticide breeds a new generation of mosquitoes that are resistant to that particular insecticide.

"Insecticides sprayed on house walls or bed nets are some of the most successful ways of controlling malaria," said Andrew Read, professor of biology and entomology, Penn State. "But they work by killing the insects or denying them the human blood they turn into eggs. This imposes an enormous selection in favor of insecticide-resistant mosquitoes."

Read and his colleagues Matthew Thomas, professor of entomology, Penn State, and Penelope Lynch, doctoral student, Open University, UK, argue that insecticides -- chemical or biological -- that kill only older mosquitoes are a more sustainable way to fight the deadly disease.

"If we killed only older mosquitoes we could control malaria and solve the problem of resistant mosquitoes," said Read. "This could be done by changing the way we use existing insecticides, even by simply diluting them," he added.

Aging mosquitoes are easier to kill with insecticides like DDT but new generation pesticides could do it too. Read and his colleagues are working with a biopesticide that kills older mosquitoes.

"It is one of the great ironies of malaria," explained Read, whose team's findings appear today (April 7) in PLoS Biology. "Most mosquitoes do not live long enough to transmit the disease. To stop malaria, we only need to kill the old mosquitoes."

Since most mosquitoes die before they become dangerous, late-acting insecticides will not have much impact on breeding, so there is much less pressure for the mosquitoes to evolve resistance, explained Read, who is also associated with the Penn State Center for Infectious Disease Dynamics. "This means that late-life insecticides will be useful for much, much longer -- maybe forever -- than conventional insecticides," he added. "Insects usually have to pay a price for resistance, and if only a few older mosquitoes gain the benefits, evolutionary economics can stop resistance from ever spreading."

"We are working on a fungal pesticide that kills mosquitoes late in life," said Thomas. "We could spray it onto walls or onto treated materials such as bed nets, from where the mosquito would get infected by the fungal spores." The fungi take 10 to 12 days to kill the insects. This achieves the benefit of killing the old, dangerous mosquitoes, while dramatically reducing the selection for the evolution of resistance, Thomas explained.

To study the impact of late-acting insecticides on mosquito populations, the researchers constructed a mathematical model of malaria transmission using factors such as the egg laying cycle of the mosquito and the development of parasites within the insect.

Once malaria parasites infect a mosquito, they need at least 10 to 14 days -- or two to six cycles of egg production -- to mature and migrate to the insect's salivary glands. From there they can pass into humans when a mosquito bites.

Analyses of the model using data on mosquito lifespan and malaria development from hotspots in Africa and Papua New Guinea reveal that insecticides killing only mosquitoes that have completed at least four cycles of egg production reduce the number of infectious bites by about 95 percent.

Critically, the researchers also found that resistance to late-acting insecticides spreads much more slowly among mosquitoes, compared to conventional insecticides, and that in many cases, it never spreads at all.

Read says the development of biological or chemical insecticides that are more effective against older, malaria-infected mosquitoes could save the millions dollars that will have to be spent to endlessly find new insecticides to replace ones that have become ineffective.

"Insecticides that kill indiscriminately impose maximal selection for mosquitoes that render those insecticides useless. Late-life acting insecticides would avoid that fate," Read added. "Done right, a one-off investment could create a single insecticide that would solve the problem of mosquito resistance forever."

quote:

Op dinsdag 14 april 2009 02:10 schreef SpecialK het volgende:
tot vandaag nog nooit zelfs maar iets gehoord over Histones. Dank je!

quote:

An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence.

quote:

New Nucleotide In DNA Could Revolutionize Epigenetics

ScienceDaily (Apr. 17, 2009) — Anyone who studied a little genetics in high school has heard of adenine, thymine, guanine and cytosine – the A, T, G and C that make up the DNA code. But those are not the whole story. The rise of epigenetics in the past decade has drawn attention to a fifth nucleotide, 5-methylcytosine (5-mC), that sometimes replaces cytosine in the famous DNA double helix to regulate which genes are expressed. And now there's a sixth: 5-hydroxymethylcytosine.

In experiments to be published online April 16 by Science, researchers reveal an additional character in the mammalian DNA code, opening an entirely new front in epigenetic research.

The work, conducted in Nathaniel Heintz's Laboratory of Molecular Biology at The Rockefeller University, suggests that a new layer of complexity exists between our basic genetic blueprints and the creatures that grow out of them. "This is another mechanism for regulation of gene expression and nuclear structure that no one has had any insight into," says Heintz, who is also a Howard Hughes Medical Institute investigator. "The results are discrete and crystalline and clear; there is no uncertainty. I think this finding will electrify the field of epigenetics."

Genes alone cannot explain the vast differences in complexity among worms, mice, monkeys and humans, all of which have roughly the same amount of genetic material. Scientists have found that these differences arise in part from the dynamic regulation of gene expression rather than the genes themselves. Epigenetics, a relatively young and very hot field in biology, is the study of nongenetic factors that manage this regulation.

One key epigenetic player is DNA methylation, which targets sites where cytosine precedes guanine in the DNA code. An enzyme called DNA methyltransferase affixes a methyl group to cytosine, creating a different but stable nucleotide called 5-methylcytosine. This modification in the promoter region of a gene results in gene silencing.

Some regional DNA methylation occurs in the earliest stages of life, influencing differentiation of embryonic stem cells into the different cell types that constitute the diverse organs, tissues and systems of the body. Recent research has shown, however, that environmental factors and experiences, such as the type of care a rat pup receives from its mother, can also result in methylation patterns and corresponding behaviors that are heritable for several generations. Thousands of scientific papers have focused on the role of 5-methylcytosine in development.

The discovery of a new nucleotide may make biologists rethink their approaches to investigating DNA methylation. Ironically, the latest addition to the DNA vocabulary was found by chance during investigations of the level of 5-methylcytosine in the very large nuclei of Purkinje cells, says Skirmantas Kriaucionis, a postdoctoral associate in the Heintz lab, who did the research. "We didn't go looking for this modification," he says. "We just found it."

Kriaucionis was working to compare the levels of 5-methylcytosine in two very different but connected neurons in the mouse brain — Purkinje cells, the largest brain cells, and granule cells, the most numerous and among the smallest. Together, these two types of cells coordinate motor function in the cerebellum. After developing a new method to separate the nuclei of individual cell types from one another, Kriaucionis was analyzing the epigenetic makeup of the cells when he came across substantial amounts of an unexpected and anomalous nucleotide, which he labeled 'x.'

It accounted for roughly 40 percent of the methylated cytosine in Purkinje cells and 10 percent in granule neurons. He then performed a series of tests on 'x,' including mass spectrometry, which determines the elemental components of molecules by breaking them down into their constituent parts, charging the particles and measuring their mass-to-charge ratio. He repeated the experiments more than 10 times and came up with the same result: x was 5-hydroxymethylcytosine, a stable nucleotide previously observed only in the simplest of life forms, bacterial viruses. A number of other tests showed that 'x' could not be a byproduct of age, DNA damage during the cell-type isolation procedure or RNA contamination. "It's stable and it's abundant in the mouse and human brain," Kriaucionis says. "It's really exciting."

What this nucleotide does is not yet clear. Initial tests suggested that it may play a role in demethylating DNA, but Kriaucionis and Heintz believe it may have a positive role in regulating gene expression as well. The reason that this nucleotide had not been seen before, the researchers say, is because of the methodologies used in most epigenetic experiments. Typically, scientists use a procedure called bisulfite sequencing to identify the sites of DNA methylation. But this test cannot distinguish between 5-hydroxymethylcytosine and 5-methylcytosine, a shortcoming that has kept the newly discovered nucleotide hidden for years, the researchers say. Its discovery may force investigators to revisit earlier work. The Human Epigenome Project, for example, is in the process of mapping all of the sites of methylation using bisulfite sequencing. "If it turns out in the future that (5-hydroxymethylcytosine and 5-methylcytosine) have different stable biological meanings, which we believe very likely, then epigenome mapping experiments will have to be repeated with the help of new tools that would distinguish the two," says Kriaucionis.

Providing further evidence for their case that 5-hydroxymethylcytosine is a serious epigenetic player, a second paper to be published in Science by an independent group at Harvard reveals the discovery of genes that produce enzymes that specifically convert 5-methylcytosine into 5-hydroxymethylcytosine. These enzymes may work in a way analogous to DNA methyltransferase, suggesting a dynamic system for regulating gene expression through 5-hydroxymethylcytosine. Kriaucionis and Heintz did not know of the other group's work, led by Anjana Rao, until earlier this month. "You look at our result, and the beautiful studies of the enzymology by Dr. Rao's group, and realize that you are at the tip of an iceberg of interesting biology and experimentation," says Heintz, a neuroscientist whose research has not focused on epigenetics in the past. "This finding of an enzyme that can convert 5-methylcytosine to 5-hydroxymethylcytosine establishes this new epigenetic mark as a central player in the field."

Kriaucionis is now mapping the sites where 5-hydroxymethylcytosine is present in the genome, and the researchers plan to genetically modify mice to under- or overexpress the newfound nucleotide in specific cell types in order to study its effects. "This is a major discovery in the field, and it is certain to be tied to neural function in a way that we can decipher," Heintz says.

quote:

The Story Of X: Evolution Of A Sex Chromosome

ScienceDaily (Apr. 25, 2009) — Move over, Y chromosome – it's time X got some attention.

In the first evolutionary study of the chromosome associated with being female, University of California, Berkeley, biologist Doris Bachtrog and her colleagues show that the history of the X chromosome is every bit as interesting as the much-studied, male-determining Y chromosome, and offers important clues to the origins and benefits of sexual reproduction.

"Contrary to the traditional view of being a passive player, the X chromosome has a very active role in the evolutionary process of sex chromosome differentiation," said Bachtrog, an assistant professor of integrative biology and a member of UC Berkeley's Center for Theoretical Evolutionary Genomics.

Bachtrog, UC Berkeley post-doctoral fellow Jeffrey D. Jensen and former UC San Diego post-doc Zhi Zhang, now at the University of Munich, detail their findings in this week's edition of the open-access journal PLoS Biology.

"In our manuscript, we demonstrate for the first time the flip side of the sex chromosome evolution puzzle: The X chromosome undergoes periods of intense adaptation in the evolutionary process of creating new sections of the genome that govern sexual differentiation in many species, including our own," she said.

Not all animals and plants employ genes to determine if an embryo becomes male or female. Many reptiles, for example, rely on environmental cues such as temperature to specify male or female.

But in life forms that do set aside a pair of chromosomes to specify sex – from fruit flies to mammals and some plants – the two X chromosomes inherited by females look nearly identical to the other non-sex chromosomes, so-called autosomes, Bachtrog said. The Y chromosome, however, which is inherited by males in concert with one X chromosome, is a withered version of the X, having lost many genes since it stopped recombining with the X chromosome.

In mammals, that probably took place about 150 million years ago, while in the fruit fly Drosophila melanogaster, a laboratory favorite, the sex chromosomes arose independently about 100 million years ago. In both humans and fruit flies, the Y chromosome has dwindled from a few thousand genes to a few dozen.

Hence the intense interest in why and how the Y chromosome lost genes once it stopped interacting with the X. Scientists have found that, as the only chromosome pair that doesn't break and recombine every time a cell divides, the XY pair in males is unable to take advantage of the main way deleterious genetic mutations are eliminated. The XX pair in females does recombine, but for the Y, the only way to get rid of a bad mutation in a gene is to inactivate or delete the entire gene. Over millions of years, inactive genes are lost, and the Y shrinks.

"If you have no recombination, natural selection is less effective at removing detrimental genes," said Bachtrog. "Y is an asexual chromosome, and it pays a price for that: It keeps losing genes."

Bachtrog, whose career has revolved mostly around the study of the degeneration of the Y chromosome, decided to focus on the X chromosome several years ago and went about searching for sex chromosome pairs that have arisen more recently – and thus might be in the process of adapting to their new role. Her paper centers around study of the three sex chromosomes in a rare western fruit fly, Drosophila miranda, a darker-colored cousin of D. melanogaster. (Many creatures have more than one pair of sex chromosomes; the platypus, for example, has five pairs, all inherited together.)

While one of D. miranda's sex chromosomes is descended from the original sex chromosome that appeared in Drosophila nearly 100 million years ago, a second originated perhaps 10 million years ago, and the third about a million years ago. The older two look much alike, Bachtrog said: The Y chromosome in each pair has lost genes to become a shadow of its former self, while the two X chromosomes are indistinguishable from each other.

The third and youngest sex chromosome is different. The Y is not yet shriveled, though it contains many non-functional genes – about half the total – that will eventually be lost. The X, which is dubbed neo-X, is undergoing rapid change, however, with about 10 times the normal amount of adaptation seen in the autosomes, according to the researchers.

By adaptation, Bachtrog means that the gene sequences in the X chromosome are becoming fixed as random mutations have finally settled on a few beneficial changes that accommodate the increasingly irrelevant Y chromosome. Between 10 and 15 percent of neo-X genes show adaptation, compared to only 1-3 percent of autosome genes.

"In hindsight, that is not surprising," Bachtrog said. "Neo-X is facing a much more challenging situation than the autosomes because its pair, the Y chromosome, is degenerating. Its genes are no longer producing proteins, so neo-X has to compensate by up-regulating its genes. We find a lot of genes on the X chromosome are involved in dosage compensation."

In humans, for example, all genes on the X chromosome are twice as active to account for the lack of genes on the Y. Women accommodate this by inactivating one entire X chromosome so as not to produce too much protein, Bachtrog said.

Another change in neo-X that Bachtrog suspects is taking place is the elimination of genes that are harmful to females. Biologists have realized recently that some genes have opposite effects in males and females, and evolution is a tug of war between males jettisoning genes that they find detrimental only to have females put them back, and vice versa.

"A good place to put sexually antagonistic genes that are beneficial to one sex but detrimental to the other is on the sex chromosomes," she said. The Y always ends up in the male, she said, so genes on the Y chromosome won't affect females.

"Conversely, the X chromosome becomes feminized with genes that are good for the female but detrimental to the male," said Bachtrog, adding that the X also becomes demasculinized, losing genes that are of use only in the male.

In search of more insights into the evolution of the X chromosome, Bachtrog said she is looking for fruit fly species with older and younger sex chromosomes "to study sex chromosome evolution in action." She said evidence suggests that adaptation to being a sex chromosome is most intense between 1 and 10 million years after it starts. Bachtrog also is completing assembly of the genome sequence for D. miranda, which is not among the 12 species of Drosophila currently targeted by the genome sequencing community. She hopes that the fly will become a model system like D. melanogaster.

"Now, finally, we are within reach of studying model systems like D. miranda that we couldn't think of several years ago," she said, predicting that "whole genome comparisons will revolutionize evolutionary biology, ecology and many other fields."

quote:

Evolution Of Human Sex Roles More Complex Than Described By Universal Theory

ScienceDaily (Apr. 27, 2009) — A new study challenges long-standing expectations that men are promiscuous and women tend to be more particular when it comes to choosing a mate. The research suggests that human mating strategies are not likely to conform to a single universal pattern and provides important insights that may impact future investigations of human mating behaviors.

In 1948, Angus J. Bateman's performed some now famous studies in fruit flies that showed that males exhibit greater variance in mating success (the number of sexual partners) and in reproductive success (the number of offspring) when compared to females. In addition, Bateman demonstrated that there was a stronger relationship between reproductive success and mating success in males than females.

Bateman concluded that, because a single egg is more costly to produce than a single sperm, the number of offspring produced by a female fruit fly was mainly limited by her ability to produce eggs, while a male's reproductive success was limited by the number of females he inseminated. These studies supported the conventional assumption that male animals are competitive and promiscuous while female animals are non-competitive and choosy.

"The conventional view of promiscuous, undiscriminating males and coy, choosy females has also been applied to our own species," says lead study author Dr. Gillian R. Brown from the School of Psychology at the University of St. Andrews. "We sought to make a comprehensive review of sexual selection theory and examine data on mating behavior and reproductive success in current human populations in order to further our understanding of human sex roles."

Dr. Brown and colleagues examined the general universal applicability of Bateman's principles. To test one of Bateman's assumptions, they collated data on the variance in male and female reproductive success in 18 human populations. While male reproductive success varied more than female reproductive success overall, huge variability was found between populations; for instance, in monogamous societies, variances in male and female reproductive success were very similar.

The researchers also examined factors that might explain variations across human populations that are not in keeping with the prediction of universal sex roles. "Recent advances in evolutionary theory suggest that factors such as sex-biased mortality, sex-ratio, population density and variation in mate quality, are likely to impact mating behavior in humans," concludes Dr. Brown. "The insights gained from this new perspective will have important implications for how we conceive of male and female sexual behavior."

quote:

Neandertals Sophisticated And Fearless Hunters, New Analysis Shows

ScienceDaily (May 14, 2009) — Neandertals, the 'stupid' cousins of modern humans were capable of capturing the most impressive animals. This indicates that Neandertals were anything but dim. Dutch researcher Gerrit Dusseldorp analysed their daily forays for food to gain insights into the complex behaviour of the Neandertal. His analysis revealed that the hunting was very knowledge intensive.

Although it is now clear that Neandertals were hunters and not scavengers, their exact hunting methods are still something of a mystery. Dusseldorp investigated just how sophisticated the Neandertals' hunting methods really were. His analysis of two archaeological sites revealed that Neandertals in warm forested areas preferred to hunt solitary game but that in colder, less forested areas they preferred to hunt the more difficult to capture herding animals.

The Neandertals were not easily intimated by their game. Rhinoceroses, bisons and even predators such as the brown bear were all on their menu. Dusseldorp established that just as for modern humans, the environment and the availability of food determined the choice of prey and the hunting method adopted. If the circumstances allowed it, Neandertals lived in large groups and even the most attractive and difficult to catch prey were within their reach.

Coordination and communication

Although herding animals are difficult to surprise and isolate, many such game lived on the open steppes. This large supply attracted large groups of Neandertals. That the Neandertals were capable of hunting down such elusive game demonstrates that they had good coordination skills and could communicate well with each other.

Each prey has a specific cost-benefit scenario. For example, game that are more difficult to catch yield more calories and have a more usable, thick fleece. Dusseldorp used these data to examine the Neandertal's preferences. He also analysed the prey of hyenas in the same manner. Hyenas were important competitors of Neandertals as they had a similar dietary pattern.

Dusseldorp demonstrated that Neandertals, thanks to their intelligence, even surpassed hyenas at capturing the strongest game. All things being considered, the Neandertals were skilled and highly intelligent hunters. So the idea that Neandertals were brute musclemen can be dismissed.

This study was part of NWO project "Thoughtful Hunters? The Archaeology of Neandertal Communication and Cognition." Dusseldorp is continuing his research with a postdoc position in Johannesburg. There he shall focus on the modern humans that evolved in Africa.

quote:

Hutchinson, J.R. and Allen, V. (2009) The evolutionary continuum of limb function from early theropods to birds. Naturwissenschaften, 96, 423-448

The bipedal stance and gait of theropod dinosaurs evolved gradually along the lineage leading to birds and at some point(s), flight evolved. How and when did these changes occur? We review the evidence from neontology and palaeontology, including pectoral and pelvic limb functional morphology, fossil footprints/trackways and biomechanical models and simulations. We emphasise that many false dichotomies or categories have been applied to theropod form and function, and sometimes, these impede research progress. For example, dichotomisation of locomotor function into ‘non-avian’ and ‘avian’ modes is only a conceptual crutch; the evidence supports a continuous transition. Simplification of pelvic limb function into cursorial/non-cursorial morphologies or flexed/columnar poses has outlived its utility. For the pectoral limbs, even the classic predatory strike vs. flight wing-stroke distinction and separation of theropods into non-flying and flying—or terrestrial and arboreal—categories may be missing important subtleties. Distinguishing locomotor function between taxa, even with quantitative approaches, will always be fraught with ambiguity, making it difficult to find real differences if that ambiguity is properly acknowledged. There must be an ‘interpretive asymptote’ for reconstructing dinosaur limb function that available methods and evidence cannot overcome. We may be close to that limit, but how far can it be stretched with improved methods and evidence, if at all? The way forward is a combination of techniques that emphasises integration of neontological and palaeontological evidence and quantitative assessment of limb function cautiously applied with validated techniques and sensitivity analysis of unknown variables.