Contrasting patterns of evolution following whole genome versus tandem duplication events in Populus [RESEARCH]

Contrasting patterns of evolution following whole genome versus tandem duplication events in Populus [RESEARCH]:
Comparative analysis of multiple angiosperm genomes has implicated gene duplication in the expansion and diversification of many gene families. However, empirical data and theory suggest that whole-genome and small-scale duplication events differ with respect to the types of genes preserved as duplicate pairs. We compared gene duplicates resulting from a recent whole genome duplication to a set of tandemly duplicated genes in the model forest tree Populus trichocarpa. We used a combination of microarray expression analyses of a diverse set of tissues and functional annotation to assess factors related to the preservation of duplicate genes of both types. Whole genome duplicates are 700 bp longer and are expressed in 20% more tissues than tandem duplicates. Furthermore, certain functional categories are over-represented in each class of duplicates. In particular, disease resistance genes and receptor-like kinases commonly occur in tandem but are significantly under-retained following whole genome duplication, while whole genome duplicate pairs are enriched for members of signal transduction cascades and transcription factors. The shape of the distribution of expression divergence for duplicated pairs suggests that nearly half of the whole genome duplicates have diverged in expression by a random degeneration process. The remaining pairs have more conserved gene expression than expected by chance, consistent with a role for selection under the constraints of gene balance. We hypothesize that duplicate gene preservation in Populus is driven by a combination of subfunctionalization of duplicate pairs and purifying selection favoring retention of genes encoding proteins with large numbers of interactions.

Células tronco e perspectivas na cura da cegueira

Não minha gente, não foi um pastor nem milagreiro -- Usando células tronco embrionárias, cientistas foram capazes de curar dois pacientes considerados definitivamente cegos em decorrência de doenças degenerativas. Após vários meses, os pacientes não demonstraram qualquer sinal de rejeição ou propensão a formação de tumores.

Embora ainda seja cedo para afirmar que o tratamento servirá para todos imediatamente, mas sem dúvidas apresenta uma esperança para aqueles que sofrem sem poder enxergar o mundo a sua volta.

O artigo completo pode ser encontrado aqui: http://press.thelancet.com/stemcelleyes.pdf

GenomeView: a next-generation genome browser

GenomeView: a next-generation genome browser:
Due to ongoing advances in sequencing technologies, billions of nucleotide sequences are now produced on a daily basis. A major challenge is to visualize these data for further downstream analysis. To this end, we present GenomeView, a stand-alone genome browser specifically designed to visualize and manipulate a multitude of genomics data. GenomeView enables users to dynamically browse high volumes of aligned short-read data, with dynamic navigation and semantic zooming, from the whole genome level to the single nucleotide. At the same time, the tool enables visualization of whole genome alignments of dozens of genomes relative to a reference sequence. GenomeView is unique in its capability to interactively handle huge data sets consisting of tens of aligned genomes, thousands of annotation features and millions of mapped short reads both as viewer and editor. GenomeView is freely available as an open source software package.

Roche to buy Illumina?

Será ? Sem dúvidas um negócio desse porte iria rearranjar todo o mercado de sequenciadores de nova geração.
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Roche to buy Illumina?: Looks like Roche want a chunk of Illumina. There are press releases on both companies websites (Illumina and Roche) about Roches offer. There is little on the Illumina release except confirmation about the unsolicited acquisition proposal at $44.50 per share, this amounts of $5.7Bn according to Roche and is a 64% premium on current stock price.

Roche speak about the combination of the two companies and a strengthening of diagnostics potential. They also state that the will merge headquarters to the San Diego Illumina site (who incidentally just built nice new offices).

The press release quotes Roche's CEO Severin Schwan as saying "It is our strong preference to enter into a negotiated transaction with Illumina, and we remain willing to engage in a constructive dialogue" whether Illumina are so eager is another thing entirely.

Dear Jay... the press release finishes with a letter from Franz Humer (Roche Chairman) to Jay Flatley (Illumina CEO). It says a lot about the unwillingness of Illumina to engage and how great the merger will be for both companies.


I had also heard that Qiagen were hovering over Illumina. Illumina have been incredibly successful over the past five or six years, I am not surprised someone is wiling to pay a lot of money to buy them. Is $44.50 good enough? I am not sure, especially given the price was nearly $80 last Summer.

A man for our season

Post muito interessante, retirado do blog do Sean Eddy.
Traz uma coleção de artigos que nos faz refletir sobre a realidade da comunidade científica.
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A man for our season:

Peter Lawrence and Michael Locke wrote an essay that made an enormous impression on me (“A Man for Our Season”, Nature, 1997). For a long time a copy hung on the wall of the lab. I was reminded of it last week when I read a recent interview with Lawrence (“The Heart of Research is Sick”, Lab Times, 2011).

When it’s hard to reach me because I’m busy with my own research work; when I have to decline to travel to give seminars; when postdocs in my lab publish their own independent work without my name on their papers; when our papers go to open-access journals that do a good job of delivering substantive content regardless of that journal’s supposed “impact”; when I spend time on the details of a constructive peer review; when I help HHMI recruit and mentor younger scientists — and indeed when I moved to Janelia Farm, to be part of the idealistic culture that we want to build here — it’s principles much like Peter Lawrence’s that I’m aspiring to.

Real lives and white lies in the funding of scientific research
PLoS Biology, 2009

Retiring retirement

Nature, 2008

The mismeasurement of science

Current Biology, 2007

Men, women, and ghosts in science

PLoS Biology, 2006

The politics of publication

Nature, 2003

Rank injustice

Nature, 2002

Science or alchemy?

Nature Reviews Genetics, 2001

A man for our season

Nature, 1997

Computer gamers solve problem in AIDS research that puzzled scientists for years | Not Exactly Rocket Science

Mais uma demonstração de que as vezes a criatividade é capaz de superar desafios incríveis.
Interessante a iniciativa de incorporar as soluções propostas pelos gamers em um software para predição de estrutura de proteínas.

Computer gamers solve problem in AIDS research that puzzled scientists for years | Not Exactly Rocket Science:

When scientists struggle with a problem for over a decade, few of them think, “I know! I’ll ask computer gamers to help.” That, however, is exactly what Firas Khatib from the University of Washington did. The result: he and his legion of gaming co-authors have cracked a longstanding problem in AIDS research that scientists have puzzled over for years. It took them three weeks.

Khatib’s recruits played Foldit, a programme that reframes fiendish scientific challenges as a competitive multiplayer computer game. It taps into the collective problem-solving skills of tens of thousands of people, most of whom have little or no background in science. Here’s what I wrote about Foldit last year:

The goal of the game is to work out the three-dimensional structures of different proteins. Proteins are feats of biological origami; they consist of long chains of amino acids that fold into very specific and complicated shapes. These shapes can reveal how proteins work, but solving them is fiendishly challenging. To do it, scientists typically need to grow crystals of purified protein before bouncing X-rays off them.

Foldit takes a different approach, using the collective efforts of causal gamers to do the hard work. And its best players can outperform software designed to do the same job. Best of all, you don’t need a PhD to play Foldit. Barely an eighth of the players work in science, and two-thirds of the top scorers have no biochemistry experience beyond high school. The controls are intuitive; tutorial levels introduce the game’s mechanics; colourful visuals provide hints; and the interface is explained in simple language. While protein scientists concern themselves with “rotating alpha-helices” and “fixing degrees of freedom”, Foldit players simply ‘tweak’, ‘freeze’, ‘wiggle’ and ‘shake’ their on-screen shapes.

Foldit’s success relies on the fact that it doesn’t shallowly flirt with interactivity – it’s a true game. Its creator Seth Cooper designed it to “attract the widest possible audience… and encourage prolonged engagement”. It’s competitive: players are scored based on the stability of the structures they end up with and a leader board shows how they rank against other gamers. There’s also a social side: gamers can chat on online forums, work in groups to solve puzzles and share solutions on a wiki. And just like real game development, everything was tuned according to feedback from the players. Tools were added and refined, the difficulty of the tutorials was tweaked to stop frustrated beginners from leaving, and puzzles were matched to the skills of the players.

There’s the thrill of contributing to genuine scientific research, but that motivates less than half of the community. The rest do it for the achievement, the social aspects and largely, because the game was fun and immersive.

Foldit’s origins lie within Rosetta, a piece of software designed to solve protein structures by simulating and testing thousands of different folds. Rosetta is an example of ‘ distributed computing’, where volunteers run the program on their home computers when they don’t need it. They effectively donate their computing power to speed up the laborious task of solving protein structures. But the volunteers wanted to use their biological computers – their brains – as well as their man-made ones. They suggested an interactive version of the programme and in May 2008, they got their wish with Foldit.

Last year, Cooper showed that Foldit’s gamers were better than the Rosetta programme at solving many protein structures. They used a wide range of strategies, they could pick the best places to begin, and they were better at long-term planning. Human intuition trumped mechanical number-crunching.

This year, Khatib wanted to see if the Foldit community could solve fresh problems. He entered the players into a twice-yearly contest called CASP (Critical Assessment of Techniques for Protein Structure Prediction), where structural biologists from all over the world compete to predict the structures of proteins that have almost been solved. They get the best predictions from Rosetta to begin with. Then, they’re on their own.

Khatib’s gamers, bearing names such as Foldit Contenders Group and Foldit Void Crushers Group, had varying degrees of success in the contest. In many of the categories, they did reasonably well but they couldn’t match the best groups. They weren’t as good at using the structures of similar proteins to tweak the ones they were working on. They could also head down dead ends if they started at the wrong place. In one case, their strategy of refining their starting structures to the best possible degree led to one of the “most spectacular successes” in the contest. But mostly, they focused too heavily on tweaking already imperfect solutions that other teams achieved better results by making large-scale changes.

Learning from that lesson, Khatib stepped in himself. He agitated the initial protein structures in many random ways, to create a wide variety of terrible answers that the gamers could then refine. In their attempts, they came up with the best-ranked answer to the most difficult challenge in the competition.

It was a success, and more would follow. After the competition, the players solved an even more important problem. They discovered the structure of a protein belonging to the Mason-Pfizer monkey virus (M-PMV), a close relative of HIV that causes AIDS in monkeys.

These viruses create many of their proteins in one big block. They need to be cut apart, and the viruses use a scissor enzyme –a protease – to do that. Many scientists are trying to find drugs that disable the proteases. If they don’t work, the virus is hobbled – it’s like a mechanic that cannot remove any of her tools from their box.

To disable M-PMV’s protease, we need to know exactly what it looks like. Like real scissors, the proteases come in two halves that need to lock together in order to work. If we knew where the halves joined together, we could create drugs that prevent them from uniting. But until now, scientists have only been able to discern the structure of the two halves together. They have spent more than ten years trying to solve structure of a single isolated half, without any success.

The Foldit players had no such problems. They came up with several answers, one of which was almost close to perfect. In a few days, Khatib had refined their solution to deduce the protein’s final structure, and he has already spotted features that could make attractive targets for new drugs.

“This is the first instance that we are aware of in which online gamers solved a longstanding scientific problem,” writes Khatib. “These results indi­cate the potential for integrating video games into the real-world scientific process: the ingenuity of game players is a formidable force that, if properly directed, can be used to solve a wide range of scientific problems.”

Update: Stephen Curry, who works on protein structures, had this to say about the paper: “Credit where it’s due: this is certainly an innovative approach to the problem of determining crystal structures of proteins. And I do like the idea of ‘citizen science’. Although it’s probably questionable how much science the gamers are understanding, the involvement in this sort of research, even if it is just at the level of playing a game, is undoubtedly a good thing.”

Curry also points out that a structure for this protein was published in 2003 using a different method called nuclear magnetic resonance. Khatib says that this is “quite inaccurate” and that people have struggled to use it to progress any further, but Curry says that they don’t say much about the differences between the old and new structures.

Likewise, Khatib doesn’t mention how closely related the M-PMV protease and the HIV ones are. “This information is crucial for deciding whether a structure of M-PMV protease is going to be any use as a template for the design of novel classes of drug targeted to HIV protease. If I had reviewed this paper, I would have asked for that information to be included because it is needed to make sense of observed differences in structure,” he says.

Reference: Khatib, DiMaio, Foldit Contenders Group, Foldit Void Crushers Group, Cooper, Kazmierczyk, Gilski, Krzywda, Zabranska, Pichova, Thompson, Popović, Jaskolski & Baker. 2011. Crystal structure of a monomeric retroviral protease solved by protein folding game players. Nature Structural and Molecular Biology http://dx.doi.org/10.1038/nsmb.2119

More on Foldit: Foldit – tapping the wisdom of computer gamers to solve tough scientific puzzles

Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes.

Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes.: Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes.

Nat Genet. 2011 Dec;43(12):1275-80

Authors: Lieberman TD, Michel JB, Aingaran M, Potter-Bynoe G, Roux D, Davis MR, Skurnik D, Leiby N, LiPuma JJ, Goldberg JB, McAdam AJ, Priebe GP, Kishony R

Abstract

Bacterial pathogens evolve during the infection of their human host(1-8), but separating adaptive and neutral mutations remains challenging(9-11). Here we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple individuals. We conducted a retrospective study of a Burkholderia dolosa outbreak among subjects with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired nonsynonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes affect important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition and implicate oxygen-dependent regulation as paramount in lung infections. Several genes have not previously been implicated in pathogenesis and may represent new therapeutic targets. The identification of parallel molecular evolution as a pathogen spreads among multiple individuals points to the key selection forces it experiences within human hosts.
PMID: 22081229 [PubMed - indexed for MEDLINE]

Identifying Single Copy Orthologs in Metazoa

Identifying Single Copy Orthologs in Metazoa:

by Christopher J. Creevey, Jean Muller, Tobias Doerks, Julie D. Thompson, Detlev Arendt, Peer Bork

The identification of single copy (1-to-1) orthologs in any group of organisms is important for functional classification and phylogenetic studies. The Metazoa are no exception, but only recently has there been a wide-enough distribution of taxa with sufficiently high quality sequenced genomes to gain confidence in the wide-spread single copy status of a gene.
Here, we present a phylogenetic approach for identifying overlooked single copy orthologs from multigene families and apply it to the Metazoa. Using 18 sequenced metazoan genomes of high quality we identified a robust set of 1,126 orthologous groups that have been retained in single copy since the last common ancestor of Metazoa. We found that the use of the phylogenetic procedure increased the number of single copy orthologs found by over a third more than standard taxon-count approaches. The orthologs represented a wide range of functional categories, expression profiles and levels of divergence.
To demonstrate the value of our set of single copy orthologs, we used them to assess the completeness of 24 currently published metazoan genomes and 62 EST datasets. We found that the annotated genes in published genomes vary in coverage from 79% (Ciona intestinalis) to 99.8% (human) with an average of 92%, suggesting a value for the underlying error rate in genome annotation, and a strategy for identifying single copy orthologs in larger datasets. In contrast, the vast majority of EST datasets with no corresponding genome sequence available are largely under-sampled and probably do not accurately represent the actual genomic complement of the organisms from which they are derived.

Evolutionary biology: A ratchet for protein complexity

Evolutionary biology: A ratchet for protein complexity:

Evolutionary biology: A ratchet for protein complexity

Nature 481, 7381 (2012). doi:10.1038/nature10816
Authors: W. Ford Doolittle