READING A PAPER OUTSIDE OF MY RESEARCH FOCUS

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Brain development guided by ‘Junk DNA’

The colossal mistake of labeling 90% of the genome as ‘Junk’ is still coming back to haunt biologists. The more we look at the genome the more complex it becomes; this latest development puts junk DNA right at the forefront of brain development.

The DNA in question here codes for something called a ‘long non-coding RNA’ (lncRNA, pronounced ‘link-RNA’). These RNA molecules were only recently discovered and their functions are only just starting to be uncovered. These lncRNA molecules do not code for proteins, hence they were not thought to influence the cells inner workings, new research is showing just how wrong this hypothesis was.

LncRNAs are thought to bind proteins to chromosome, the structures that contain the DNA in the cell, by doing this they influence which genes are ‘switched on’ and ‘switched off’ – an important process in development.

Researchers, in a new paper [1], describe how computational analysis linked about 2000 lncRNAs to cells involved in neurodegenerative disorders such as Alzheimer’s and Huntington’s disease. The results suggest that these lncRNAs are key in turning genes on and off at the right time when cells develop in the brain.

Much more research is needed in this area;  it only goes to show that the more we look at life, the more complex it becomes!

References

[1] Ramos et al., Integration of Genome-wide Approaches Identifies lncRNAs of Adult Neural Stem Cells and Their Progeny In Vivo, Cell Stem Cell (2013), http://dx.doi.org/10.1016/j.stem.2013.03.003

ScienceDaily: here 

Image credit: Mikael Häggström and Andrew Gillies

Twists and turns in DNA communication

When an embryo is developing genes need to be turned on and off in a very controlled manner, this allows a cell to become a specific type of cell (e.g. a muscle cell) in the right place, at the right time. These genes are turned on and off by different proteins called growth factors, but here’s the catch; genes must be precisely regulated by these growth factors, but what precisely regulates the growth factors in the first place?

One factor - Fibroblast growth factor 8 (Fgf8) – has now been studied in a lot of detail, and new findings are astonishing [1]. FgF8 controls itself through a number of independent modules on the DNA, the location of these models is very important; they don’t just have to be in the correct linear order, but also in the correct 3D orientation. The DNA in the genome forms large loops; the loops bring these DNA modules that are very far away in the DNA sequence, close together so that they can interact and activate the Fgf8 gene.

This represents a very complex, yet often overlooked, aspect of genomic regulation. The press release by the EMBL research institute [2] states:

“We showed that the surprisingly complex organisation of this genomic region is a key aspect of the regulation of Fgf8….

These findings highlight a level of complexity of gene regulation that is often overlooked. Regulatory elements are not engaged in a one-to one relationship with the specific gene that has the appropriate DNA sequence. The local genomic organisation, and 3D folding of DNA, might actually be more important factors that both modulate the action of regulation elements, and put them in contact with their target gene.”

This is genomic engineering of unprecedented complexity in an information processing system that far exceeds the complexity and elegance of anything humans have constructed so far. Below is part of a figure from the paper to help you visualise the 3D organisation.

[1] Marinić, M. et al. 2013. An integrated holo-enhancer unit defines tissue and gene specificity of the Fgf8 regulatory landscape.Developmental Cell.24 (5): 530-542. 

[2] European Molecular Biology Laboratory, 2013. DNA’s twisted communication. EMBL Press Release posted on wwwemblde on February 28, 2013, accessed March 29, 2013. 

Image credit:  EMBL/Mirna Marinić

Cutting through the spin: “Living Fossil” genome sequence unveiled

The scientific community is buzzing at the moment with the publication of the African coelacanth, or Latimeria chalumnae, genome sequence. Now scientists are hoping that the sequence will answer some crucial questions concerning the ‘water to land’ transition, the paper is even ambitiously titled “The African coelacanth genome provides insights into tetrapod evolution” and lead author Chris Amemiya boldly stated: 

“The coelacanth is a cornerstone for our attempt to understand tetrapod evolution”.

But reports have been a bit vague and woolly on the actual evolutionary aspects and impliactions, so I thought I’d dive into the paper and take a look at what was really going on. Here are a few thoughts on the key points:

Coelacanth genes evolve more slowly

The main finding of the paper was the mutation rate of coelacanth protein coding genes was approximately half that of tetrapods. This has ruffled a few feathers, especially those of evolutionary biologist Larry Moran who runs the ‘Sandwalk’ blog. He says:

“This extraordinary claim [slower evolving genes] flies in the face of everything we know about molecular evolution

...

The coelacanth data make no sense. You should be very skeptical.

 
You should also wonder about the kind of people that Nature asks to review their papers. Reviewers may not be inclined to challenge the data but they should challenge the conclusions and they should ask the authors to address the fact that their interpretation is inconsistent with the modern evolutionary theory.”

I feel I need to explain why this claim that the genes evolve more slowly is a bit odd. The paper claims the slow evolution rate is because the coelacanth does not ‘need’ to evolve. This is a bit ridiculous because the main thrust of modern evolutionary biology is that variation occurs regardless of whether it is ‘needed’. Different organisms have different mutation rates but the differences aren’t normally this drastic. Genomes change continuously through mutation and the only way to stop a genome changing through the generation is to 1) stop new variants i.e. mutants appearing, this is quite improbable. Or 2) Have a strong selective pressure that eliminates variants as they appear. Changing the mutation rate this drastically is unlikely and there is little evidence for strong selective pressure on the coelacanth genome, hence the data for the coelacancth is a bit odd. BUT the data does agree with previous findings supporting a slowly evolving genome [1,2].

There are a number of possible reasons to explain this:

1) Larry Moran is correct and the data is completely wrong. There were, in fairness, only a few DNA samples to work with and other researchers have pointed out problems with the ‘slow evolution’. 

2) The data is inconsistent with the modern evolutionary theory because the modern evolutionary theory is incomplete

3) Coelacanth genes do not evolve as slowly as thought because coelacanths aren’t as old as scientist think. (A possible creationist interpretation, but this perspective would require details on how you detect rates of evolution which is too long and boring to go into and explain now)

For now we’ll just have to wait and see what happens, hopefully we might see the genome sequence of the Indonesian coelacanth so we can have a proper comparison.

Tetrapods (four limbed vertebrates) are more closely related to lungfish, not the coelacanth

Sorry, the coelacanth isn’t the missing link you’ve been waiting for.

So called ‘adaptions’ to land

News articles have been boldly proclaiming that the coelacanth provides critical clues to the evolution of life on land. However when I read the paper these ‘critical clues’ were very underwhelming and just seemed to be some very unsurprising findings with a bit of evolutionary gloss. Here’s a few of them:

1. Tetrapods are missing 50 genes found in coelacanths. Wow, its almost as though they are different animals. This is glossed over with phrases such as “supporting the idea that they were lost in the tetrapod lineage.” when really this is just a basic scientific observation about which genes are present and which are absent with an evolutionary ‘loss’ story woven in. 

2. More than 50 genes that tetrapods are missing from tetrapods were analysed were found to be important in embryonic development of fish, but genes critical for the basic development were the same (just like in all vertebrates ever looked at). My my, it’s almost as though the fish has fish specific development genes and some of the same critical genes found in all life, there is nothing unexpected or revealing about this data, you probably could have predicted it.

3. Tetrapods have some different conserved non-coding elements than fish. These differences were found to be mostly in smell perception protein regulation. The authors say this:

“may reflect the necessity of a more tightly regulated, larger and more diverse repertoire of olfactory [smell] receptors for detecting airborne odorants as part of the terrestrial lifestyle”

I mean, yes, but it really doesn’t tell you much about the actual evolution, it simply tells you that fish and tetrapods have different regulation of olfactory receptors, no real surprise there at all.

4. Tetrapods have some different conserved non-coding elements regulating there body plans. Again, one may get the impression you were comparing two different kinds of animals or something.

5. One more that I want to quote straight out of a sciencedaily article:

“The Urea cycle. Fish get rid of nitrogen by excreting ammonia into the water, but humans and other land animals quickly convert ammonia into less toxic urea using the urea cycle. Researchers found that the most important gene involved in this cycle has been modified in tetrapods.”

i.e. the gene is different in tetrapods and fish, wow.

There were a few more bits and bobs but I think you get the picture. This paper makes good observations but layers on the evolutionary gloss to bring some kind of great evolutionary achievement out of this paper. But before we move on I want to draw you attention to one difference that has somehow been left out of every news report I’ve read so far. The coelacanth lacks the IGM gene. This is surprising because the Immunoglobulin M (IGM) gene has been found in every vertebrate looked at to date (which is a lot!). The gene codes for the first antibody (a protein that attacks infectious) to be produced once the immune system recognizes a threat. So where is it? This is fairly crucial if the last common ancestor of bony fish and vertebrates is missing one of the most crucial and most common genes around. Funny that no one seems to have mentioned this….

That concludes my quick thoughts on this genome, I hope you found it useful since Its always good to split the science from the story telling. Hopefully there will be some new insights from this genome soon. 

References and sources

[1] Amemiya, C. T. et al. Complete HOX cluster characterization of the coelacanth provides further evidence for slowevolution of its genome. Proc.Natl Acad. Sci.USA 107, 3622–3627.

[2] Larsson, T. A., Larson, E. T. & Larhammar, D. Cloning and sequence analysis of the neuropeptide Y receptors Y5 and Y6 in the coelacanth Latimeria chalumnae. Gen. Comp. Endocrinol. 150, 337–342 (2007).

Paper: Chris T. Amemiya et al. The African coelacanth genome provides insights into tetrapod evolution. Nature, 2013; 496 (7445): 311 DOI:10.1038/nature12027

ScienceDaily: Here 

Biomimicry – A parasite inspired surgical adhesive

You probably haven’t heard of the parasitic worm Pomphorhynchus laevis, but now this little worm has been thrown into the limelight because it is the inspiration for a rather neat surgical adhesive.

P. laevis has a strange trick up its sleeve: it enters the gut of the fish host and then its proboscis (shown in the picture below) swells up to press hundreds of tiny microneedles in to the host intestine wall; this firmly secures the worm into the intestine of the host.

In a recent Nature communications paper [1] researchers describe how this parasite inspired a new kind of surgical adhesive.  The researchers created a patch made of plastic that is covered with microneedles (see below). These needles penetrate the tissue, and then a thin layer of hydrogel, a material that expands when it gets wet, on each needle swells and holds the patch securely in place.

There are many potential advantages to this new patch. Firstly, since it does not involve a chemical adhesive the patient is less likely to have an allergic reaction to the patch. Secondly, the needles are only a quarter of the length of surgical staples  so there is less tissue damage once the staples are removed, reducing the chance of infection.

Currently the patch is being tested for use in skin grafts, but they have many potential uses. They can be used to hold the sides of a wound or incision open during surgery, delivering therapeutics to an open wound and potentially, this is really cool, they may one day be used inside the body if a slowly dissolving patch can be developed.  

I’ll let Dr Scott Somers, from the NIH’s National Institute of General Medical Science, have the last word: 

“Drawing on how parasitic worms attach to and feed on fish, they have designed a way to close surgical wounds that appears better than anything currently available for clinical use.”

 Image above: The patch (left) and the mechanism of action (right).

[1] Yang, Seung Yun, et al. “A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue.” Nature Communications 4 (2013): 1702.

Science daily:  Here

I may have spent all day writing science papers

I don’t need friends 

Big Bang in Big Trouble?

We’re going to take a slight detour from biochemistry to the world of physics because interesting things may be happening. Some people like to cry that the Big Bang theory has been proven many times, however they forget they forget that in science things are not ‘proven’ and the winds of evidence can quickly change if you are willing to throw yourself into the messy world of experimental science. Here’s the latest from the physics world:

The European Space Agency’s Planck mission team recently released what they describe as ‘the most detailed map ever created of the cosmic microwave background’, the radiation supposed to be left over from the big bang, and the results were interpreted as being in line with what was expected from standard cosmology and the predictions of the Big Bang.  According to the preliminary analysis (available on the preprint sever) the findings support the idea that the universe underwent a short time of rapid expansion – inflation (not the financial kind) – in accordance with Big Bang cosmology.

However, things may not be as rosy as they seem. Another recent paper by Paul Steinhardt et al argues that the inflation paradigm (a paradigm is basically the most commonly used ‘working model’) may be in serious trouble.

Inflation was originally proposed in the 1980s to explain the presence of anomalies in the cosmic microwave radiation (CMR). Although largely accepted by the scientific community, little is known about what caused the inflation. Current proposals include a complex interplay between various factors including the ‘Higgs Field’ and the ‘Inflation Field’, once the inflation field energy dominates over the Higgs field, inflation occurs. Different inflation models have been proposed with different energies and other complicated physics things that I’m sure someone somewhere would love to talk to you about, but what has this got to do with new data?

Steinhardt and others note that the models which are supported by the new Planck data are far less likely to occur naturally than the models that the new data rules out. To further the problem, when the data was analysed with data from the Higgs field (mentioned earlier) from the large Hadron collider (LHC), the data from the LHC suggests that the Higgs field started off in a high energy state. This would cause inflation to stop far too early and cause the universe to fold into a black hole, not form the universe that we know today.

In the abstract of the paper Steinhardt states (my emphasis):

“[narrowing down the models using the new data] exacerbates both the initial conditions problem and the multiverse-unpredictability problem and it creates a new difficulty which we call the inflationary “unlikeliness problem.” Finally, we comment on problems reconciling inflation with a standard model Higgs, as suggested by recent LHC results. In sum, we find that recent experimental data disfavors all the best-motivated inflationary scenarios and introduces new, serious difficulties that cut to the core of the inflationary paradigm”

I mentioned in my previous post that science papers tend to be boring and make modest claims, well claiming that the inflation paradigm has serious core cutting difficulties then is pretty darn strong language in science!

David Spergel, of Princeton University agrees that there is confusion concerning the initial conditions that were needed for the Universe to emerge:

“There are significant conceptual problems with all of our ideas about the early Universe,” 

So how are these problems addressed? Steinhardt favours the ‘cyclical model’ of Big Bangs and Big Crunches, whilst others hang on to the standard model.

Does this new data actually disprove the Big Bang model? No, theories of this scale are not shot down by one paper or one piece of evidence, however it’s interesting to note that secular opponents of the Big Bang are becoming more vocal and are being noticed in the scientific community. One thing is sure, scientifically we are far from a complete understanding of the early universe and there are many many questions still to be answered, nothing is sure and nothing is sacred.

Having said that, I believe the Big Bang, or variations thereof, will always be around. If you do not hold that there is a God who can create out of nothing then a Big Bang type scenario is the only option you have for how the universe came into existence. Your only alternative universe is one which is eternal and that seems very unlikely.

I hope you’ve enjoyed this excursion into physics; normal biochemistry service will be resumed shortly.

Source: Nature News - Higgs data could spell trouble for leading Big Bang theory