New Research visitor – Dr. Marco Fondi

We are pleased to welcome a new visitor to our research group – Dr. Marco Fondi.

Dr. Fondi is joining us for six months as part of a Science Foundation Ireland funded project on understanding networks in biology.

Marco has been working at the Dipartmento di Biologia Evoluzionistica in the Laboratorio di Evoluzione Microbica e Molecolare.

In the last four or five years, Dr. Fondi has made some significant findings in the whole area of analysing gene fusions, recombination and the evolution of plasmids.

Post-doctoral applicants sought for IRCSET grants.

At November 19, 2011
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post-doc applicants wanted

We are looking for post-doctoral applicants for the upcoming IRCSET grant deadline. The name of the programme is EMPOWER and it is aimed at relatively early-stage postodoctoral applicants. Here is some of the information form the website:

EMPOWER: Government of Ireland Postdoctoral Fellowships in Science, Engineering and Technology
IRCSET will continue to offer their sought-after fellowships based at an Irish host laboratory. The candidates must have been employed for no more than 36 months as a postdoctoral researcher before the closing date of the Call, and propose pursuing their work for 24 months at an Irish research laboratory. They must be able to provide evidence of at least one significant research output, such as a published peer-reviewed article or equivalent intellectual property output. For more detailed information on the eligibility criteria, please download the ‘EMPOWER Terms & Conditions’ document from the EMPOWER page. Applications for EMPOWER will be accepted via one call for Postdoctoral Fellowships in autumn each year.

We are looking for applicants for the Pisani, Fitzpatrick and McInerney laboratories.

If you have been working in the areas of bioinformatics and/or molecular evolution, please feel free to contact us through our contact page. The deadline for completed applications is December 7th, 2011.

Survival of the sexiest

This is to announce that on Tuesday next (the 15th of November), there will be a talk given by Dr. James McInerney in JH2 in the John Hume Building at NUI Maynooth at 7:30pm, entitled:

Survival of the sexiest: Why females want a mate with a good sense of humour, a brightly coloured tail and nice antlers.

The event is open to the public and is part of Science week and there is no admission charge.

Please share this notice using the social network links below.

Where are you all coming from?

The new website has had about 1,500 visitors, so welcome to all of you. If you want to know where you all have come from, here you go….

SMBE2012 in Dublin

The annual meeting of the Society for Molecular Biology and Evolution will be held in Dublin next June from the 23rd to the 26th. In the coming week we will make the decisions on which symposia will be included in the final programme. This will be a great thing on one hand, because we get to see who is likely to speak at the meeting, what they are proposing to speak about and we get to see for the first time what the science is going to look like. But because we will have to turn some people down, I guess that is the downside. In any case, by Friday of this week the conference will begin to take shape for the first time and that is quite exciting. Below is a promotional video for people travelling to Ireland

Research returns to Ireland far exceed investment

by Dick Ahlstrom

Financial returns from Ireland’s expenditure in research have easily outstripped the original investment, according to a study released on 19 September.
It claims that while the Exchequer put in almost €1.2 billion over the period 2000-2006 the returns amounted to about €1.8bn.
The study by PA Consulting said that the figure for returns was probably a gross underestimate. This was because it decided against including financial returns—for example, from the construction phase—and measured only the direct commercial impact of expenditure, according to the report’s authors.

It did not attempt to factor in the enhanced ability to attract direct foreign investment from an improved science infrastructure or the indirect returns from downstream contracts and the value of the skills base arising from investment in research.

“As such, the study presents a minimum valuation of impact at this stage,” the authors concluded, so the results were “very encouraging”.
The minister of state for science, Sean Sherlock, welcomed the report, saying it underlined the positive impact of Exchequer investment in R&D.
It also showed that the benefits measured by commercial returns for companies were weighted towards the later years of the study period. Given the type of investment involved, “it is to be expected that the full effect will only be realised over an extended period of time”, Sherlock said.

PA Consulting was asked by the Higher Education Authority to assess the financial impact of Exchequer investment in research. The authority is the body through which money flows into the higher education sector but it also manages a key research funding scheme, the Programme for Research in Third Level Institutions (PRTLI).
The study looked at 45 investments in research centres and other initiatives funded via the PRTLI in 2000-2006. The consultants assessed the impact of the spend on the current and anticipated income derived as a direct result of the investment.

The report identified 50 companies which together valued returns so far at €753 million. The companies estimated that accumulated returns over the coming five years would add a further €1.11bn to reach a total of €1.86bn.

PVC bacteria are not half-way to being eukaryotes

Over the past few years, manuscripts have been appearing in the literature that have been suggesting that PVC (Planctomycetes, Verrucomicrobia, Chlamydia) bacteria are in many ways like Eukaryotes and consequently, they are an excellent system for understanding eukaryote biology and indeed this group of bugs actually gave rise to modern eukaryotes.

This is complete nonsense.

So, where does this idea come from? Well, some PVC bacteria have their DNA enclosed in a membrane and under a microscope this looks a bit like a eukaryote nucleus, they have ‘compartments’ in their cells and so do eukaryotes and they lack some things that eukaryotes lack -peptidoglycan, for instance.

However, the key to understanding evolution is the understanding of the difference between homology and analogy.

Homology means one specific thing – descent from a common ancestor. It does not mean similarity. Famously, Walter Fitch said that homology was like pregnancy: you cannot be 80% pregnant and two evolving entities cannot be 80% homologous. They are either homologous or they are not.

Now that we have a good definition of homology, we have the seriously difficult problem of identifying homologs.

For morphological characters, making homology statements is usually a matter of having a really careful look at the organs in question. Getting a better microscope, for instance, if you need a greater level of detail. We expect that morphological characters that are homologous will display similarity in many of their details – their structure, their function etc.

For molecular characters, it can turn out to be more difficult. We only have four nucleotides or twenty amino acids. We usually try to make statements of homology by using a similarity search of databases and deciding that if two sequences showed a higher level of similarity than you might expect to see by random chance, then we make a leap of faith and infer that they are homologs. However, our homology statements can be confounded by a number of issues. Some sequences might manifest high levels of similarity as a consequence of simple repetition of residues. They might really be homologues, but sequence divergence has been so great that sequence similarity is not longer apparent. They might also not be homologues, but convergent evolution has resulted in compositional similarity that makes them look homologous.

In order to correctly infer homology for molecular sequence data we need careful and rigorous analysis of the sequences and maybe their structures and when no other explanation can be offered for their similarity, then and only then might we agree that two sequences are homologous.

Our next task when we discover homologous sequences is to ask how they came to being in the organisms in which they are seen.

For many genes, the reason why two organisms have homologous in their genomes is because the gene copies were passed down from one generation to the next at cellular or organismal reproduction time. However, for other organisms, the reason why they have homologs is because these homologues were acquired via horizontal gene transfer.

Therefore, if we are to say that the PVC bacteria are of special interest for studying eukaryotic origins, then we need to be able to say that they are the closest relatives of extant eukaryotes and that they share genes and structures because of vertical acquisition of genes.

Ultimately, when you look at the data, you can see that PVC bacteria do not share a lot of homologous structures exclusively with eukaryotes and are therefore no more useful in the study of eukaryotes than any other bacterium would be.

If you want more details on this, please see our recent paper on the issue:

McInerney, J. O., Martin, W. F., Koonin, E. V., Allen, J. F., Galperin, M. Y., Lane, N., Archibald, J. M. and Embley, T. M. (2011), Planctomycetes and eukaryotes: A case of analogy not homology. BioEssays. doi: 10.1002/bies.201100045. [link]

Seeking post-doctoral applicants

At September 17, 2011
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We are actively looking for early-stage researchers (must have been, or expect to be awarded their PhD in 2011) to apply for Sir Henry Wellcome post-doctoral research funding. We are specifically interested in all aspects of horizontal or lateral gene transfer as it relates to biomedical problems. Our research methods are usually bioinformatic, but we are happy to think about a combination of wet bench work and bioinformatics. Please get in contact with us. The deadline for applications is November 1st, 2011, so in order to put an application together, the potential applicant needs to get in touch immediately. Please tweet, email, FaceBook share or otherwise distribute this link. See buttons below.

Pisani lab work on Tardigrades.

Today the Irish Independent ran a nice report on Davide Pisani’s recent publication on the phylogenetic position of Tardigrades. The work is reported in Proceedings of the National Academy of Sciences, USA. Here’s the link.

Goods thinking versus tree-thinking

Goods-thinking versus Tree-thinking

In the famous Monty Python “Dead Parrot” sketch, John Cleese returns to a pet shop where he has just bought a parrot and asks for his money back. The reason being that the parrot is in fact dead.

This seems to be a not unreasonable request on the part of the purchaser – on buying a parrot, there is a reasonable expectation that it might be alive.

However, true to Monty Python form, the owner of the pet shop disagrees and goes to extreme lengths to try to suggest that the parrot is not in fact dead, merely sleeping.

I cannot go through the sketch, you will have to take a look for yourself below, however, this sketch reminds me of those scientists who are still trying to support the notion of the Tree of Life.

The Tree of Life is the phrase used for the hypothesis that the evolution of life on the planet can be adequately accounted for by drawing a single phylogenetic tree depicting the relationships of all the evolving entities on the planet.

Darwin thought this was a neat idea and one of the iconic Darwin images is his drawing of a tree.

Darwin, however, did not know anything about plasmids, viruses or horizontal gene transfer. Therefore, he made no comments on how these might affect tree-like representations of life on the planet.

Everything went swimmingly for the ToL hypothesis for zoologists and botanists for pretty much all of the 20th century. Even with the advent of molecular sequence data, there was no real objection to the hypothesis.

However, microbiologists could not seem to get their part of the tree organised. Depending on what kind of character you used – morphology, motility, biochemistry – you got a different tree. The characters did not tend agree with one another. Microbiology faltered a little as a discipline and suffered from not having the kind of all-encompassing systematic footing as zoology and botany.

By the 1950s, microbiologists had largely given up on the microbial tree and focussed instead on what bugs did, rather than how they were related.

Carl Woese led the charge to change this and proposed that because all cells had ribosomal RNA sequences, this could be used as a proxy tree and everybody seemed happy with that.

Then genomes came along and we were right back where we started – different gene trees tended not to agree with each other completely. They did agree a little bit and sometimes a lot. But they tended to disagree in significant ways.

However, rather than say that the tree of life hypothesis is now dead – no single unifying tree could be constructed that encompassed all life – the tree-thinkers kept insisting that the parrot tree was not dead, it was simply sleeping.

For some of us this was not good enough. If it ain’t a tree, then it ain’t a tree.

Some people like Eugene Koonin and Pere Puigbo have looked at statistical trends among phylogenetic trees and have seen how there is a single trend that is to be found in “nearly universal trees” – genes that are widespread in nature – and that as a consequence, this is the “statistical tree of life”. Unfortunately, for me, any graph that represents only about 1.6% of all the data is really only a tiddler of a graph (no offence).

We have recently published a manuscript that advocates that we take all current ideas about the existence of a great “Tree of Life” and we finally let them go. We say “they are no more”, they are dead parrots.

Let’s just imagine that genes are ‘goods’, like air or water or screws or wheels. We know that these goods can be passed around, we know that they can be put together in new combinations (a chair can be made of steel and foam and wood, or just wood or tin and plastic) and when looked at objectively, we an see that genes or bits of genes can be considered to be goods.

So, right there things are different. We don’t start with a tree and then try to explain everything with reference to the tree. We start with the molecules. We allow them to be recombined together – a happens all the time in nature. We don’t force them to be in cells – thereby accommodating plasmids, phage, viruses etc.

We then interpret the similarity of gene trees by simply looking at how these goods are inherited – vertically and horizontally.

What is the consequence of these two mechanisms of inheritance? Well, genes that are inherited together should have similar gene trees.

Genes that tend to be passed around through horizontal transfer on their own will have a different evolutionary history to other genes.

…and this is the pattern that we see.

The public goods hypothesis also immediately suggests categories of genes and these categories (public, private, club or common goods) immediately suggest a larger influence of ecology in evolution. Selection modifies how a gene is inherited and who inherits it. The tree of life hypothesis had little to do with environment and selection.

In our view, we don’t think Darwin was wrong – the Tree of Life hypothesis is simply a ‘regionalized’ hypothesis. It explains some things, but doesn’t explain everything.

Goods-thinking should replace tree-thinking, but I guess we will only know this retrospectively.

Here is the dead parrot sketch.