Daniel

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Ego sum Daniel
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  • February 21, 2012
  • 08:39 PM
  • 117 views

An exercise in open science: The evolution of voltage-gated sodium channels

by Daniel in Ego sum Daniel

>> This post describes my re-analysis of the voltage-gated sodium channel α subunit (SCNA) gene family evolution, based on a previously published study. I have shared the improved results as well as all source files and datasets openly in Figshare, together with a description of the methods: link.

This is probably not my last re-analysis of the same dataset, and I'd want to encourage others to use other phylogenetic methods on our alignments, or use our alignments to analyse their own SCNA sequences.

Last year my research group published a study on the evolution of voltage-gated sodium channel α subunits (see reference below) with me as one of the co-authors. Voltage-gated sodium channels are the proteins that permit the passage of positive charges, in this case sodium ions, across the cell membranes of neurons and thus make it possible for your nerve fibres to fire electrical signals. The α subunits are the very large proteins forming the actual pore that selects only sodium ions and allows them to pass. It's difficult to overestimate how essential they are for the function of the nervous system, and how important their evolution has been for the evolution of neuronal signaling.

Our published study used both sequence-based phylogenetic data and genomic data to clear up the muddled relationships between different subtypes of voltage-gated sodium channels in vertebrates. Us humans, and most other mammals, have ten different types of these α subunits, encoded by genes of the SCNA family. The different subtypes have acquired different properties and are expressed in different parts of the nervous system and some other tissues in the body where electrical signaling is necessary. One of the subtypes, the product of the SCN7A gene, has even evolved to such a degree that it's not a channel anymore. It's probably more like a sodium "sensor". There are also specific diseases, different types of epilepsy, seizures and paralyses, that are associated with mutations of the various subtypes.

The same gene family in true bony fishes (teleosts) encodes up to eight different subtypes, almost as many as the mammalian family. The funny evolutionary twist is that we have evolved almost the same amount of subtypes by completely different mechanisms! In tetrapods, the fleshy-limbed mostly terrestrial group that we belong to, local duplications of genes on the same chromosomes gave rise to new subtypes, while in teleost fishes it was their ancestral duplication of the whole genome that did the same on different chromosomes! You can see the difference in the image below.


Chromosome organization of the SCNA genes and some of their neighboring genes in humans and zebrafish. Each numbered line represents a different chromosome. The ten human genes are named in a series from SCN1A to SCN11A, skipping the number 6. The duplicates in teleost fish are denoted by the letters "a" and "b".

This means that when doing comparative studies, it's important to know that while all vertebrate voltage-gated sodium channels have a common origin, they're not always directly related to each other.

Using more powerful and careful methods than we'd used before, I made new evolutionary trees that agree even better with these conclusions. Most of all these new trees are better and clearer examples of the evolutionary relationships between different voltage-gated sodium channel subtypes. You can see figures of the new trees and access all the source files and datasets in Figshare.

While our previous study solved the evolutionary relationships between different SCNA subtypes, we had to rely on the genomic data on the chromosome locations of the genes to solve some inconsistencies in the original phylogenetic trees. Our study was the first to do phylogenetic analyses from alignments of the whole α subunit sequences, which are over 2000 amino acids long! This work was almost entirely carried out by my colleague Jenny Widmark and our supervisor Dan Larhammar. The fact that most previous studies had only analysed parts of the proteins was the reason they had reached the wrong conclusions about how different subunits were related.

Assembling and aligning all that sequence data from the genomic sequences of multiple vertebrate species took a lot of time and thought, so I thought it would be a shame not to use it to find out if better methods could solve what the published tree couldn't and if they could provide more and better evidence for our conclusions, especially when all the different analyses are considered together.

As a summary, I put together this tree over the relationships between the different human subtypes. As you can see, the positions of the different subtypes in the trees agree with the chromosome locations.


The most up-to-date view of the relationship between the different human voltage-gated sodium channel subtypes (the names of the proteins are in parenthesis), based on my latest re-analyses. Teleost fish have duplicates of SCN4A, SCN8A and the genes that gave rise to SCN5A, -10A and -11A and SCN1A, -2A, -3A, -9A and -7A respectively.

Previous analyses put some of the more divergent subtypes, like the products of the SCN11A and SCN7A genes at the base of the tree when they are in fact some of the newest subtypes! Now we can also say that SCN4A and the SCN5A, -10A, -11A-group are more closely related, and that SCN8A and the SCN1A, -2A, -3A, -9A, -7A-group are more closely related. You can see some the older analyses that don't actually give the correct evolutionary view displayed on IUPHAR's* database of receptors and ion channels (link). Another example is displayed in Wikipedia (link).

The next step is to contact IUPHAR and ask them to review our new data so that our updated view of the voltage-gated sodium channels reaches all the people it potentially benefits, everyone doing functional research on sodium channels. To do that I think an open science approach is clearly the best way to go.

* The International Union of Basic and Clinical Pharmacology decides on "official" receptor and ion channel nomenclature, among other things.

Widmark, J., Sundstrom, G., Ocampo Daza, D., & Larhammar, D. (2010). Differential Evolution of Voltage-Gated Sodium Channels in Tetrapods and Teleost Fishes Molecular Biology and Evolution, 28 (1), 859-871 DOI: 10.1093/molbev/msq257
... Read more »

Widmark, J., Sundstrom, G., Ocampo Daza, D., & Larhammar, D. (2010) Differential Evolution of Voltage-Gated Sodium Channels in Tetrapods and Teleost Fishes. Molecular Biology and Evolution, 28(1), 859-871. DOI: 10.1093/molbev/msq257  

  • December 1, 2011
  • 03:31 PM
  • 238 views

Two ways of looking at the same proteins: Insulin-like Growth Factor Binding Proteins

by Daniel in Ego sum Daniel

Back in June I blogged about a research paper that we had just published with myself as the lead author. The subject of our paper was the evolution of the Insulin-like Growth Factor Binding Proteins (IGFBPs), and how this family of proteins has expanded in vertebrate evolution. Yesterday I noticed that this paper, "my" paper!, now has received its very first citation! This was a my first paper as lead author, so naturally I avidly checked it out.

The research paper that cites us is in press in the Journal of Biological Chemistry (reference below). While we were interested in finding as many IGFBP genes in as many vertebrates as we could, studying the characteristics of their genetic code and establishing their evolution, this study is more concerned with the biochemical structures of the actual proteins.


Molecular model of mouse IGFBP-5 (N-terminal), showing the locations of the cysteines that form disulfide bridges. Ref: M. Nili et. al. (see reference below).

Through mass spectrometry, the authors of this study, Mahta Nili and co-workers, have determined the presence of so called disulfide bridges in the IGFBP-5 protein from mouse. Disulfide bridges are formed by the side-chain of the amino acid cysteine and are important structural components of proteins, holding different parts of the three-dimensional structure together and in a way giving the protein part of its "shape". And when it comes to proteins, if you want to understand functions, you have to understand "shape". They could conclude that the structure of the mouse IGFBP-5, looking at the disulfide bridges, probably is very similar to the structure of most other IGFBPs (IGFBP -1,-2,-3 and -4), but not all (IGFBP-6). This is based on comparisons with already known models of a few other IGFBPs as well as our analyses of the amino acid sequences encoded by many different IGFBP genes. Their concluding citation of our paper reads:

Overall, as depicted in Fig. 5C [see above - Daniel], it is likely that the three-dimensional structure of the N-terminal domain of IGFBP-5 is very similar to IGFBP-4, and we predict that IGFBPs 1 - 3 will exhibit analogous structural features.
I agree with their prediction! It's "my" paper they're citing. Our evolutionary analyses would also allow them to say that the structure (probably) holds across all vertebrates, and that it is the ancestral one, but they haven't gone as far as stating that outright.

These are two very different ways of looking at the structure/function relationship of proteins. But at the center of both approaches is trying to connect the biochemical structures of proteins to their functions and their evolution. Each angle feeds the other. Considering all the similarities between IGFBPs I think it's a bit of an evolutionary mystery why we have so many of them - we found some fishes probably have up to 11, us mammals have 6. The structure that the authors of this new study have determined is of the part of IGFBPs (IGFBP-5 in this case) that binds to the Insulin-like Growth Factors (IGFs). This interaction regulates many molecular processed behind our metabolism, cell proliferation and growth, especially during embryonic development, so clearly this functional element is important. But maybe more clues to the evolution of several and diverse IGFBPs lie in other functional elements that have nothing to do with IGFs? Several such biological functions have been described for some IGFBPs, and in our paper from earlier this year we could start suggesting that some of the amino-acids that could underlie these IGF-independent functions show up in some IGFBPs and species, and not in others.

Still, it's only by determining the three-dimensional biochemical structures of proteins that we can start developing an idea about the evolution of functional elements in protein sequences, and how they relate to function.

Nili, M., Mukherjee, A., Shinde, U., David, L., & Rotwein, P. (2011). Defining the disulfide bonds of insulin-like growth factor binding protein-5 by tandem mass spectrometry with electron transfer dissociation and collision induced dissociation Journal of Biological Chemistry DOI: 10.1074/jbc.M111.285528

Ocampo Daza D, Sundström G, Bergqvist CA, Duan C, & Larhammar D (2011). Evolution of the Insulin-Like Growth Factor Binding Protein (IGFBP) Family. Endocrinology, 152 (6), 2278-89 PMID: 21505050

... Read more »

  • September 29, 2011
  • 10:15 AM
  • 247 views

Is there anything fish don't do? Tool use!

by Daniel in Ego sum Daniel

This video and story have been making the rounds on the Internet in the last few days. I just saw it yesterday and it's fascinating! For the first time (allegedly), "tool-use" in a fish has been filmed and the behavior is available for all of us to see. The fish in question is a species of wrasse observed in Palau, Choerodon anchorago or orange-dotted tuskfish.



You can see the fish digging out a clam with its pectoral fin, then carrying it over to a rock or a coral head and cracking it with a characteristic sideways motion of the head. The fish was observed doing this three times in a row, the last of which was recorded. Each event lasted less than five minutes. Here are summaries of the story from Scientific American, Science Daily and AnimalWise.

This finding is being published as a short notice in the journal Coral Reefs and joins other findings from earlier this year, published in the same journal, presenting the first photographic evidence of the same behavior in another species of tuskfish, Choerodon schoenleinii. That story was summarized in Science Now and Wired Science. In fact, there have been a handful of reports of the same behavior from different species of wrasse indicating that this might be a shared ancestral behavior in the Labridae.

Whether this constitutes "real" tool use as seen in mammals and birds, or not, will depend entirely on the kind of definition you use. That question is boring to me. But I do think it would be a mistake to equate or compare this "tool use" in fish to, for example, tool use in chimpanzees. Instead I think the interesting perspective is to put this behavior within the already known complex feeding and food seeking behaviors in fish to see in which niches "tool use" might have been beneficial.

Bernardi, G. (2011). The use of tools by wrasses (Labridae) Coral Reefs (Online First™, 20 September 2011) DOI: 10.1007/s00338-011-0823-6

Jones, A., Brown, C., & Gardner, S. (2011). Tool use in the tuskfish Choerodon schoenleinii? Coral Reefs, 30 (3), 865-865 DOI: 10.1007/s00338-011-0790-y

... Read more »

  • September 8, 2011
  • 12:53 PM
  • 428 views

Some notes on the Atlantic cod genome, and fish genomes in general

by Daniel in Ego sum Daniel

Teleost fish genome sequences have been absolutely essential to our understanding of vertebrate genome evolution, and to vertebrate evolution in general. Last month I welcomed the addition of the Atlantic cod genome to the sequenced fish genomes, and highlighted some of the main findings of the first analysis of the whole genome sequence. The preliminary genome database is now available for browsing at the Pre!Ensembl database.

After I had written that post, I had some notes left over because I didn't want to make my text too long. But I think they're interesting enough for me to revisit the cod genome and write a new post.


The Atlantic cod, Gadus morhua

I've already highlighted some of the basic stats of the Atlantic cod genome and compared them to some other fish genomes:

The basic genome stats reveal a pretty standard vertebrate genome, if there is such a thing. The total (haploid) size is estimated at approx. 830 million base pairs, a bit lower than previous estimates, and the number of identified genes is 22,154 (20,095 protein coding). The closest related fish species with a sequenced genome is the three-spined stickleback, Gasterosteus aculeatus, with a genome of approx. 446 million base pairs and 20,787 identified genes. The best studied fish genome, that of the zebrafish Danio rerio is quite a bit longer, with about 1.5 billion base pairs, but the gene content is similar with about 26,000 identified genes.
Aside from the zebrafish and three-spined stickleback genomes, the japanese pufferfish (Takifugu rubripes), green-spotted pufferfish (Tetraodon nigroviridis) and medaka or Japanese ricefish (Oryzias latipes) genomes have been sequenced. The medaka genome sequence is about 700 million base pairs long with about 20,400 identified genes. The two pufferfish genomes are significantly shorter, with about 390 and 340 million base pairs respectively, but with similar gene contents - about 20,400 for both species. These species represent the latest 150 - 300 million years of fish evolution, more or less, which is a great coverage, but considering the vast radiation and diversity of fishes it's a pretty thin representation - five orders out of about forty, not including the largest one Perciformes (perch-like fishes). For comparison, the genomes of over thirty different species of mammal have been sequenced (with varying quality, it should be said).


Evolutionary tree of the fish species with sequenced genomes. Divergence times between the species (million years ago) are according to timetree.org estimates, except those in cursive which are estimates from Donoghue and Benton in Trends. Ecol. Evol. 22(8), 2007. The estimate of 307 MYA for the divergence of zebra fish is probably an overestimation. Click on the image to see it larger.

Sequencing and putting together a "working" genome sequence is an arduous task. It includes the sequencing itself of innumerable small pieces of the broken-up DNA strands, then the assembly of these short fragments, called contigs, into longer pieces that can then be mapped to the different chromosomes. In this process it's also important to annotate the content of the genome - which means to identify different genes, repeat elements et c. All of this is done because the information on where different genes or other elements are located in the genome is just as important as the sequence itself. This long process is why it may take several years between the start of a genome sequencing project and the announcement and release of the sequence.

No available genome sequence, from any species, currently accounts for 100% of the genome - some parts simply seem to evade the sequencing process, either due to mistakes in the sequencing or because of the specific qualities of the particular genome region. It's also often the case that many of the short contigs cannot be assembled into large stretches of sequence, called scaffolds. This can cause a lot of trouble when it comes to puzzling the whole genome sequence together and making a map of where everything is located on the chromosomes. The zebrafish genome sequence, which is probably the best-sequenced teleost, encompasses about 87% of the projected whole genome length, which is really rather good and very "workable".

The cod genome seems to be of reasonable quality. About 90% of the estimated whole genome size is covered, but only 74% is part of the long scaffolds. The rest is made up by contigs with a minimum size of 500 base pairs that could not be put together into scaffolds. Still, it seems that these contigs represent highly variable regions, and most protein coding genes can be located within the assembled scaffold sequences. This is a good sign of quality. However, there a lot of gaps in the scaffold sequences - small regions that could not be read in the sequencing process. Together these gaps reduce the amount of the genome that was actually sequenced and assembled to about 46% of the estimated whole genome size. Since the vast majority of the already known genes could be identified, and the total gene amount is comparable to the other fish genomes, this might not be a huge problem. But it's important to remember that any genome sequencing project produces a limited dataset, not an actual whole genome.

I mentioned earlier that the cod genome database doesn't show any chromosome data. That is because the cod genome hasn't been mapped to chromosomes yet. Instead the long scaffold sequences have been compared to an existing linkage map, a collection of sequence stretches containing linked Single Nucleotide Polymorphisms, or single positions of the genome which are known to vary between individuals within the species. In this way much of the genome assembly was put together into 23 large so called linkage groups. Each different linkage group represents a number of genes that are linked with each other, which in turn is likely to represent a significant cohesive segment of a chromosome. It's these linked stretches of the genome sequence that provide the primary useful data for comparative analyses between different genomes. In total the genome sequence represented on these linkage groups is about 332 million base pairs, a match to the 46% of the genome that was actually sequenced and assembled.

By comparing these groups of linked genes to the chromosomes of the zebrafish, medaka, stickleback and green-spotted pufferfish it's possible to see that, for the most part, the same genes are linked together in all the fish genomes. This is represented by the red circles in the image below. The larger the circle, the more genes are shared between each cod linkage group and the different chromosomes in the other species.


Ref: Adapted from B. Star et al (see below).

In this way we can see that, for instance, linkage group 1 in the cod is likely to correspond to chromosome 23 in the zebrafish, 7 in the medaka, XII in the stickleback (stickleback genomes are enumerated with Roman numerals for some reason), and 9 in the pufferfish. This means that the linkage groups are likely to represent the different cod chromosomes, and that the cod shares the same basic genome organization as the other known fish genomes. There is one curious exception though - a whole block of genes in the cod linkage group 19 seem to have "changed place" compared to the other genomes. This is indicated by the blue arrows.

Overall, it seems the quality of this genome assembly is similar to the already available fish genomes. The authors of the cod genome paper note that in quality it's most similar to the medaka genome, which is not as good as the zebrafish or stickleback genomes, but better than the two pufferfish genomes and, it should be said, the majority of mammalian genomes. In my experience this means that the cod genome should be spotty in some regions, but by and large it probably contains large stretches with good "workable" sequence. I've started using it a little bit in my own research and I'm sure it's going to prove its worth.

... Read more »

Star, B., Nederbragt, A., Jentoft, S., Grimholt, U., Malmstrøm, M., Gregers, T., Rounge, T., Paulsen, J., Solbakken, M., Sharma, A.... (2011) The genome sequence of Atlantic cod reveals a unique immune system. Nature. DOI: 10.1038/nature10342  

  • August 17, 2011
  • 09:59 PM
  • 265 views

The "living fossil" discussion and that "living fossil" eel you might have heard of

by Daniel in Ego sum Daniel

I don't like the term "living fossil". Sure, when used well it can be eye-catching in a pedagogical way, but it's still sort of vague and problematic, and used badly it's outright confusing and may reinforce misconceptions about evolution. That's why when you see it used, you often see it between quotation marks followed by an explanation motivating why the organism in question is called a "living fossil" to begin with. Today we learn about the discovery of a really striking and interesting new species of eel from Palau, Protoanguilla palau, heralded as a "living fossil" in the title of the scientific publication made available today (see reference below) as well as in most media reports.


Ref: Video still/Jiro Sakaue, Southern Marine Laboratory, Palau.

As you guessed by now, I think this is a bit problematic. It starts with the fact that different people often mean different things when calling something a "living fossil". Darwin himself is acknowledged with originating the term in On the Origin of Species, if only in a passing comment. He wrote:


All fresh-water basins, taken together, make a small area compared with that of the sea or of the land; and, consequently, the competition between fresh-water productions will have been less severe than elsewhere; new forms will have been more slowly formed, and old forms more slowly exterminated. And it is in fresh water that we find seven genera of Ganoid fishes, remnants of a once preponderant order: and in fresh water we find some of the most anomalous forms now known in the world, as the Ornithorhynchus and Lepidosiren, which, like fossils, connect to a certain extent orders now widely separated in the natural scale. These anomalous forms may almost be called living fossils; they have endured to the present day, from having inhabited a confined area, and from having thus been exposed to less severe competition.

In this chapter Darwin is speaking to us about the different environmental conditions that are favorable to natural selection, or rather to the creation of new varieties through natural selection. Here he is trying to explain why some organisms might appear relatively unchanged by natural selection, using ganoid fishes, a now obsolete term describing gars and bichirs or reedfishes, the platypus and the South American lungfish, as examples of this. With "living fossil" he is vaguely referring to organisms that are the sole or almost sole survivors of a relatively old and mostly extinct lineage. This meaning is a bit different to the common use today which is either a species that appears practically unchanged from its ancestors found in the fossil record, like the gingko or the horseshoe crab, or a species that was only known from the fossil record until it was suddenly found to be very much still alive, like the coelacanth. None of these organisms fit comfortably into one coherent definition of what a "living fossil" might be without having to include several other groups that are not usually included.*

So as a term, "living fossil" is potentially misleading and awkwardly defined. But most of all it's just redundant. It's just not worth it. Some biologists see this as a reason to take the term lightly and use it casually, but I guess I just don't take many things lightly.

Discussions about "living fossils" aside, the finding of Protoanguilla palau is very interesting for several reasons. Firstly, I don't think we should underestimate the fantastic sense of wonder about our planet and about life that something like this might awake. The almost 18 cm long Protoanguilla type specimen was discovered in a cave at about 35 m of depth in the reef waters of Palau in the pacific ocean. This sort of mirrors the discovery of the coelacanth and makes you think about the kind of enigmatic species we have yet to find in the as yet unreached corners of the ocean.

Eels were one of the very first now living lineages of bony fish to emerge - it's one of the most basal. They first appear in the fossil record in the Cretaceous about 100 million years ago, but the evolution of the bony fishes as a whole probably goes back to the mid-Paleozoic, some 400-300 million years ago. Protoanguilla has an interesting combination of characters, sharing several with all other now living eels as well as with the fossil eels from the Cretaceous, some specifically only with the fossil eels. It also has yet another number of characters that are seemingly specific to it, and some that are characteristic of bony fish lineages that diverged before eels: notably, gill rakers - toothed protrusions of cartilage along the inner rim of the gills used to trap food particles - and the presence of less than 90 vertebrae. Most eels show an expansion of the vertebral column to include up to 200 vertebrae. In simple terms, it looks like an eel but it also looks really primitive. This pattern of old morphological characteristics paired with molecular phylogenetics analyses based on the mitochondrial genome place Protoanguilla at about 200 million years ago, very close to previous molecular estimations of the earliest divergence of eels and 100 million years before the first known eel fossils. The phylogenetic analyses also place it confidently within the eel lineage, so it's not a different kind of bony fish, and they show that it represents the most basal or oldest known lineage of eel. I checked the method descriptions and the results of the phylogenetic analyses in the supplementary data provided by the journal and it looks solid.

However, none of this makes Protoanguilla a "living fossil" in the same way the coelacanth or the gingko might be considered "living fossils". It doesn't conform to Darwin's original exemplification of some species as "living fossils" either. There are no "dead fossils" of Protoanguilla or similar eels as far back as 200 million years ago to begin with! Frankly, the use of the term in the title of the scientific publication is puzzling. It's the first described species in a new and basal group - why call it a "living fossil" when so much surrounding data is absent? The authors might have answered that question for me themselves in the fist sentence of the article:


Ever since Charles Darwin coined the term ‘living fossil’ in On the Origin of Species (...), organisms that have been called living fossils have received considerable attention.

They define "living fossils" as "extremely long-lived or geologically long-ranging taxa", probably based on the fact that several of the morphological characteristics of Protoanguilla seem to have appeared relatively early in evolution and have been kept since. But this definition would have to include several other groups of organisms that are usually not considered "living fossils" at all. They've strangely conflated "living fossil" with "conserved", which is a very useful and established term in evolutionary biology.

This discussion might be peripheral, but it's worth having and it comes up quite often in evolutionary biology. I really want to highlight how good the analyses in the paper are though, and how exciting the finding of Protoanguilla is for our understanding of early bony fish evolution.

For summarizing reports and videos of this marvelous animal, check out BBC News and Wired Science. Swedish newspaper Dagens Nyheter also reports - "Living fossil swims in the pacific ocean".

* Are birds "living fossils", for instance, having been the only dinosaur group out of a great number to survive extinction? I think most people would argue that they're not because they are very diverse and numerous, but there's no other reason not to include them. "Living fossil" seems to imply it should be a rare group of organisms, or ideally a single surviving species.

... Read more »

Johnson, G., Ida, H., Sakaue, J., Sado, T., Asahida, T., & Miya, M. (2011) A 'living fossil' eel (Anguilliformes: Protoanguillidae, fam. nov.) from an undersea cave in Palau. Proceedings of the Royal Society B: Biological Sciences. DOI: 10.1098/rspb.2011.1289  

  • August 12, 2011
  • 05:25 PM
  • 458 views

The Atlantic cod genome is available

by Daniel in Ego sum Daniel

Great news for those of us who are interested in comparative genomics, and fish genomes in particular - yesterday the Atlantic cod genome was made public at the cod genome project website to coincide with the description of the genome, published online in advance by Nature (reference below).

I've been pottering about in the genome since yesterday morning, looking for the gene families I'm researching in my own work, but the database is still quite rudimentary and tricky to use. Most of the sequences I've searched for come back in fragments, and since the genome hasn't been mapped to chromosomes in the database, it's difficult to find out where in the genome individual sequences are, and to "get to know the neighborhood" of the sequence you're interested in, which is essential for comparative genomics. Thankfully it will (probably) get a more user-friendly interface soon, when it becomes integrated with the Ensembl genome browser, where the other five sequenced fish genomes are already available.

I also made this illustration for my collection of genome species.


The Atlantic cod, Gadus morhua

The basic genome stats reveal a pretty standard vertebrate genome, if there is such a thing. The total (haploid) size is estimated at approx. 830 million base pairs, a bit lower than previous estimates, and the number of identified genes is 22,154 (20,095 protein coding). The closest related fish species with a sequenced genome is the three-spined stickleback, Gasterosteus aculeatus, with a genome of approx. 446 million base pairs and 20,787 identified genes. The best studied fish genome, that of the zebrafish Danio rerio is quite a bit longer, with about 1.5 billion base pairs, but the gene content is similar with about 26,000 identified genes.

Summaries of the main findings from the overall description of the cod genome are available at Nature News and Science Now. These reports highlight the main focus of the published genome description - the loss of genes essential for adaptive immune reactions. The Atlantic cod and several of its closest relatives in the family Gadidae lack genes for the Major Histocompatibility Complex class II (MHC II), one of the proteins that presents antigens to immune cells and initiate an adaptive immune response. They also lack genes for the proteins CD4 and Ii21 (also known as CD74). CD4 is expressed on lymphocytes called helper T-cells and allow them to interact with the MHC II, and Ii21 is involved in the transportation of MHC II proteins to the surface of the cell.

Instead, the Atlantic cod has greatly expanded and diversified its setup of the other class of MHC genes, the MHC class I genes, as well as genes for proteins called Toll receptors. These molecules represent another side of immune responses which, seemingly, the cod lineage has recruited to complement its immune defense. It was probably this expansion of MHC I genes and Toll receptor genes that lead to the loss of MHC II, CD4 and Ii21 rather than the other way around.

The researchers confirmed that the genes were missing, by trying to sequence them independently, with no results (which in this case was good). But from a comparative genomics perspective, the evidence they gathered is more compelling. They matched the genomic regions containing these genes in the already known fish genomes against the cod genome sequence and found the corresponding regions.


Click on the image to see a larger version. Ref: Supplementary information to B. Star et al. in Nature (see reference below).

As you can see in the image above, the yellow MHC II genes are missing from the corresponding regions of the cod genome, as compared to the zebrafish and stickleback genomes. The same thing can be seen for the Ii21/CD74 genes, but for the CD4 gene they actually found a smaller fragment of the gene in the cod genome, showing that these genes are either going or gone.

These findings helps us understand fish immunity better, and might contribute to improve the aquaculture conditions for cod, as is highlighted in the reports above, but most importantly of all it's a great and interesting example of gene loss and gene duplication, an important mechanism in evolution. In addition, the method I exemplified above is a great example of the type of work you can do once you have several whole genome sequences which you can compare with each other. Once the genomic database is fully functional, many research groups will be able to explore other great questions using similar methods. With this in mind, the cod genome promises to be yet another great contribution in our understanding of how genomes, and therefore organisms, have evolved.

Star, B., Nederbragt, A., Jentoft, S., Grimholt, U., Malmstrøm, M., Gregers, T., Rounge, T., Paulsen, J., Solbakken, M., Sharma, A., Wetten, O., Lanzén, A., Winer, R., Knight, J., Vogel, J., Aken, B., Andersen, Ø., Lagesen, K., Tooming-Klunderud, A., Edvardsen, R., Tina, K., Espelund, M., Nepal, C., Previti, C., Karlsen, B., Moum, T., Skage, M., Berg, P., Gjøen, T., Kuhl, H., Thorsen, J., Malde, K., Reinhardt, R., Du, L., Johansen, S., Searle, S., Lien, S., Nilsen, F., Jonassen, I., Omholt, S., Stenseth, N., & Jakobsen, K. (2011). The genome sequence of Atlantic cod reveals a unique immune system Nature DOI: 10.1038/nature10342
... Read more »

Star, B., Nederbragt, A., Jentoft, S., Grimholt, U., Malmstrøm, M., Gregers, T., Rounge, T., Paulsen, J., Solbakken, M., Sharma, A.... (2011) The genome sequence of Atlantic cod reveals a unique immune system. Nature. DOI: 10.1038/nature10342  

  • July 31, 2011
  • 08:22 PM
  • 469 views

Xiaotingia

by Daniel in Ego sum Daniel

The subject of feathered dinosaurs and the evolution of birds is something that fascinates me and captures my imagination, as I'm sure it does a lot of people. Not only because it changes the way we look at the world around us, specifically birds, but also because there's a lot of cool evolutionary science involved in the study of the early evolution of birds from... well, yes that's the question, isn't it? From what exactly? We know that in any evolutionary sense that matters, birds are dinosaurs, but the questions remain. How long ago did the evolution of birds start? What did the closest bird-related dinosaurs look like? What did the first birds look like, and what did they do?



A highly publicized article appeared in Nature yesterday morning, describing the lovely creature so artistically reconstructed in the image above: Xiaotingia zhengi, an early bird-like dinosaur that might help answer these questions. The findings were very quickly picked up by The Guardian, Wired Science, Not Exactly Rocket Science, Pharyngula, Live Science and Nature News, of course, among other media outlets and blogs. Partly because the archetypical "original bird" Archaeopteryx is involved. Do head over to any of those pages first for pithy summaries of the findings.

Both major Swedish newspapers were content with copying the news telegram: "Original bird was not a bird". Also here.

The description of the Xiaotingia fossil and phylogenetic analyses comparing it to other bird-like dinosaurs and early birds seems to place is together with Archaeopteryx among a dinosaur group, the Deinonychosaura, and not at the base of bird evolution. So the Xiaotingia findings call into question where the line should be drawn between birds and dinosaurs, more so than having something specific to say about Archaeopteryx itself. As with most phylogenetic trees, many of the branches are missing in the evolutionary history of the dinosaur-bird transition. The really interesting thing to consider in the light of Xiaotingia and other bird-like dinosaur findings is how beautifully gradual the transition must have been, and how remarkably early bird-like traits appeared in dinosaur evolution, in what now appears to have been a diverse and successful group of organisms. As PZ Myers put it in his Pharyngula post:


There was a whole assortment of delicate-boned, feathered, bipedal dinosaurs that were flourishing and diversifying in that window of time, and we've now got enough data that we can distinguish details in the family tree, which is absolutely fabulous.

Xu, X., You, H., Du, K., & Han, F. (2011). An Archaeopteryx-like theropod from China and the origin of Avialae Nature, 475 (7357), 465-470 DOI: 10.1038/nature10288

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  • July 22, 2011
  • 08:20 AM
  • 482 views

A quick Mendel follow-up

by Daniel in Ego sum Daniel

As a footnote to my previous post about Gregor Mendel, I offer these interesting Google NGrams.

To start off, we plot the terms "Gregor Mendel", just "Mendel", "Mendelian" as well as the genus of the garden pea Mendel worked with, "Pisum".



Not surprisingly, the years 1866 and 1900 (or there around) stand out markedly.

1866 was of course the year Mendel published his paper Experiments in Plant Hybridization, and we can see that mentions of his name, or at least his surname, and mentions of the garden pea Pisum start going up significantly. Mendel's intention with the paper was explicitly to inspire others to repeat his experiments, and he was apparently disappointed over the fact that nobody did; but it does seem like there was an awareness of his work in the late 1800s, and although the mentions of Pisum couldn't all come in reference to Mendel's work, it's remarkable how 1866 sticks out. You can repeat the experiment in German.

1900 was the year Mendel's work was re-discovered in publication and introduced to a wider scientific audience, through the independent publication of papers by Hugo de Vries, Carl Correns, Erich Tschermak and William Bateson, although none of them did immediately realize the power of Mendel's work or accepted it fully to account for the patterns of heredity they had observed in their own experiments. Nonetheless, we see that the use of the term "Mendelian" as an adjective has a large impact starting in 1900, which speaks for the introduction of Mendelian inheritance laws in a broader theoretical framework. Looking at the source data reveals mentions of "Mendelian phenomena", "Mendelian allelomorph", "Mendelian characters", "Mendelian crosses", "Mendelian factor", "Mendelian inheritance" et c.

If we plot the names of these scientists together with "Mendel" and "Mendelian", there seems to be a corresponding increase in mentions around 1900, at least for de Vries and Bateson. Although it doesn't seem to be that correlated, at first glance, with the increase in mentions of Mendel and "Mendelian". Could it be that; although de Vries, Correns and Tschermak claimed the re-discovery of Mendel for themselves, and Bateson claimed the introduction of Mendel in Britan; they themselves were not as often associated with the subsequent breakthrough of Mendel's ideas?



In my previous post I wrote about whether or not Mendel has predicted the existence of genes. While the terms "gene" and "genetic" were well in use by the early 1900s, it was William Bateson who introduced the term "genetics" as the study of biological inheritance. If we plot terms such as "Genetics", "Heredity", "Mutation", "Allele", together with "Mendel", "Mendelian", "Bateson" and "de Vries", who introduced the term "mutation", we see that the era of classical genetics that was to come in the first decades of the 1900s was already brewing when the "re-discovery" of Mendel happened. But it's undoubtable that Mendel's ideas were essential for the breakthrough of genetics in biology.



If you want to read more about the rediscovery of Mendel in 1900, I recommend the following papers as an insight into the sometimes very personal stakes involved. They were the ones I researched before writing this post.

Weinstein, A. (1977). How unknown was Mendel's paper? Journal of the History of Biology, 10 (2), 341-364 DOI: 10.1007/BF00572646

Olby, R. (2009). William Bateson's Introduction of Mendelism to England: A Reassessment The British Journal for the History of Science, 20 (04) DOI: 10.1017/S0007087400024201

Lenay C (2000). Hugo De Vries: from the theory of intracellular pangenesis to the rediscovery of Mendel. Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie, 323 (12), 1053-60 PMID: 11147091

... Read more »

Weinstein, A. (1977) How unknown was Mendel's paper?. Journal of the History of Biology, 10(2), 341-364. DOI: 10.1007/BF00572646  

Lenay C. (2000) Hugo De Vries: from the theory of intracellular pangenesis to the rediscovery of Mendel. Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie, 323(12), 1053-60. PMID: 11147091  

  • June 30, 2011
  • 01:36 PM
  • 539 views

The mighty coelacanth

by Daniel in Ego sum Daniel



I've added the above illustration of a Coelacanth (Latimeria chalumnae) to my collection of illustrations together with one I had already made of a lungfish (open image). If you like you can download both high-res TIF-files here. The same Creative Common license applies as described under the "Download Illustrations" tab above.

I was prompted to add the coelacanth after reading a recent fascinating article about the secretive lives of these marvelous fish (via Deep Sea News) by Dr. Hans Fricke and co-workers. The article summarizes decades of study of the Latimeria population outside the island Grande Comore in the Indian ocean.

Latimeria live in large overlapping home ranges that can be occupied for as long as 21 years. Most individuals are confined to relatively small home ranges, resting in the same caves during the day. One hundred and forty five coelacanths are individually known, and we estimate the total population size of Grande Comore as approximately 300–400 adult individuals. <...> We estimate that the mean numbers of deaths and newcomers are 3–4 individuals per year, suggesting that longevity may exceed 100 years.
I'm astounded and my imagination is fueled by the intimate detail and vivid language with which the individual lives of these fishes is described! From the re-sighting of known individuals across several decades, the description of their cave-dwellings, which their share in family groups, their nocturnal hunting habits, and how they sometimes move outside of their familiar home-ranges. You can also read this recent interview with Fricke in Wired.
Continue after the jump »

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Fricke, H., Hissmann, K., Froese, R., Schauer, J., Plante, R., & Fricke, S. (2011) The population biology of the living coelacanth studied over 21 years. Marine Biology, 158(7), 1511-1522. DOI: 10.1007/s00227-011-1667-x  

  • June 27, 2011
  • 07:24 PM
  • 517 views

Nicotine, appetite and the brain

by Daniel in Ego sum Daniel

Nicotine is not only very, very addictive, as a central nervous system stimulant it can also affect our motivations and behaviors in a wider sense. One of the behaviors it can modify is appetitive behavior. It's a well-funded fact that smokers tend to have a lower body-mass than non-smokers, and that smokers who quit have a tendency to gain weight, although until now the neurobiological mechanism for this modulation was unknown.

Recent findings from two different publications reveal parts of this mechanism, but while most reports have pin-pointed the results involving appetite suppression through pro-opiomelanocortin neurons, there is evidence that the complete picture is more complicated than that.
Continue after the jump »

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  • June 7, 2011
  • 12:42 PM
  • 496 views

IGFBP evolution: An interesting case of gene family expansion and retention

by Daniel in Ego sum Daniel

Or: How I really should have come up with a better title.

A small announcement: I have an article out as a first author in this month's issue of the journal Endocrinology. It's a nice journal and we spent a long time working on the manuscript so I'm very pleased that it's out. Here's a Worlde word cloud of the whole article... pretty interesting. It sums everything up pretty well actually. It's all about the evolution of the Insulin-like Growth Factor Binding Protein family of genes.


Click to see larger.

Why is it worth studying the evolutionary history of this particular gene family you might ask? It's not very well known, generally, and I bet very few know about its functions or that some members seem to be involved in certain types of cancer, for instance. Many times these gene families disappear behind esoteric acronyms and convoluted webs of functional interactions that only the initiated understand, and it's difficult to generate some sort of general interest in them. It all becomes a bit dry. But when you look a bit closer, many "obscure" (at least to the general audience) genes and proteins have a really interesting evolutionary story to tell, something that goes beyond the mere evolution of their gene sequences.
Continue after the jump »

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Ocampo Daza D, Sundström G, Bergqvist CA, Duan C, & Larhammar D. (2011) Evolution of the Insulin-Like Growth Factor Binding Protein (IGFBP) Family. Endocrinology, 152(6), 2278-89. PMID: 21505050  

  • June 3, 2011
  • 09:38 AM
  • 658 views

Turn off the lights and let melatonin run free

by Daniel in Ego sum Daniel

>> I started the following post about melatonin sometime in March to coincide with my lecture on biological rhythms on our undergrad neurobiology course. But I got really busy and then really sick so I never actually finished it. Here it is then at last.


An all too common sight, at least at my place. This is my Mac glaring. But how is our exposure to low-intensity artificial light before bedtime affecting our sleep cycle?

Twice every year I lecture to undergraduate students in biology and biomedicine about biological rhythms, specifically about circadian rhythms - how the brain regulates your daily cycle of sleep and wakefulness. In this process the small suprachiasmatic nuclei (SCN henceforth) in your hypothalamus and the hormone melatonin, secreted from your pineal gland, play very important roles. The SCN is the "internal clock" of your brain and receives light input from the eyes in order to "reset the clock" every morning, signaling that a new day has started. So daylight itself serves as a signal for the brain that it's daytime and we need to be awake and alert, as far as possible.

One of the things I tell my students that usually raises some eyebrows is that even quite low-intensity light, comparable to the illuminance from a computer or television screen, as seen above, can affect the brain and shift the circadian rhythm significantly. This knowledge goes back to experiments carried out in the mid 90's and raises questions as to how artificial light, such an obvious and constant component of our environment, is affecting our day-night cycle.

In a recently published article in the Journal of Clinical Endocrinology (reference 1 below) a team of researchers has shown indirectly that it's the interplay between the SCN and melatonin secretion, so essential to the regulation of nighttime behaviors, that is affected by the artificial light in our environment.
Continue after the jump »

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Hardeland, R., Cardinali, D., Srinivasan, V., Spence, D., Brown, G., & Pandi-Perumal, S. (2011) Melatonin—A pleiotropic, orchestrating regulator molecule. Progress in Neurobiology, 93(3), 350-384. DOI: 10.1016/j.pneurobio.2010.12.004  

Gooley, J., Chamberlain, K., Smith, K., Khalsa, S., Rajaratnam, S., Van Reen, E., Zeitzer, J., Czeisler, C., & Lockley, S. (2011) Exposure to Room Light before Bedtime Suppresses Melatonin Onset and Shortens Melatonin Duration in Humans. Journal of Clinical Endocrinology , 96(3). DOI: 10.1210/jc.2010-2098  

  • February 2, 2011
  • 10:40 AM
  • 452 views

Oxytocin, ethnocentrism and evolution (pt. 2)

by Daniel in Ego sum Daniel

I didn't want to risk making my previous post too long, and I wanted to keep it focused on "hormonal determinism", so I set aside a whole branch of my commentary on the link between the hormone oxytocin and ethnocentrism for another post. The findings I comment on were presented by De Dreu and co-workers in the latest edition of PNAS (see reference below).

So, today I want to talk briefly about bad evolutionary arguments.Continue after the jump »

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De Dreu CK, Greer LL, Van Kleef GA, Shalvi S, & Handgraaf MJ. (2011) Oxytocin promotes human ethnocentrism. Proceedings of the National Academy of Sciences of the United States of America, 108(4), 1262-6. PMID: 21220339  

  • February 1, 2011
  • 12:37 PM
  • 432 views

Oxytocin, ethnocentrism and "hormonal determinism"

by Daniel in Ego sum Daniel

There is an inordinate readiness, both within scientific circles and in popular scientific understanding, to ascribe direct causation to the actions of hormones, especially when it comes to moods and behaviors. For example, consider how you’d usually interpret the common expression “being hormonal”. I consider the thought that hormones somehow “control” our moods and behaviors a falsehood; a popular misunderstanding or oversimplification that hinders the understanding of what’s actually going on. There is just as little motivation to call a hormone the “love hormone”, the “stress hormone” or the “sleep hormone” as there is calling a gene the “gay gene” or the “god gene” et c. The idea that in fact there is no one gene for property X, Y or Z has become pretty pervasive now, and I think it’s time the same thing happened for the actions of hormones.

Within this context, I want to use as an example a newly published study in PNAS that links the actions of the neurotransmitter and hormone oxytocin to ethnocentrism – the tendency to view one’s own group, the in-group, as more important or superior to other groups.


Molecular structure of human oxytocin.

Perhaps more than any other hormone, oxytocin has become the perfect example of the kind of “hormonal determinism” that I mention above: no doubt because the study of oxytocin is a very active field and because it’s been linked to some very fascinating behaviors. Continue after the jump »

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De Dreu, C., Greer, L., Van Kleef, G., Shalvi, S., & Handgraaf, M. (2011) Oxytocin promotes human ethnocentrism. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1015316108  

De Dreu, C., Greer, L., Handgraaf, M., Shalvi, S., Van Kleef, G., Baas, M., Ten Velden, F., Van Dijk, E., & Feith, S. (2010) The Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict Among Humans. Science, 328(5984), 1408-1411. DOI: 10.1126/science.1189047  

  • December 8, 2010
  • 06:12 PM
  • 500 views

Falsehoods associated with the arsenic-thriving bacteria story: What it is and what it isn't

by Daniel in Ego sum Daniel

>> My previous post was more of a summary of what the reporting of the "NASA arsenic-thriving bacteria" story looked like from my perspective in the wake of the massive Internet onslaught of information. In this post I want to talk about how the style of communication that drove this story has lead to the dissemination of falsehoods or misconceptions that hinder a proper understanding of biology in general, regardless of the validity of the actual findings.

The aftermath
Last week I concluded that this was an interesting story with many significant possibilities, but that doubts had been raised about the validity of the findings and the scope of the conclusions that could be drawn. Already yesterday the backlash was a fact. Carl Zimmer has called up experts in the field, as well as two of the authors of the Science paper, and summarizes the aftermath in a Slate article published earlier today: "Scientists see fatal flaws in the NASA study of arsenic-based life".

None of the scientists I spoke to ruled out the possibility that such weird bacteria might exist. <...> But almost to a person, they felt that the NASA team had failed to take some basic precautions to avoid misleading results.
Much of it centers around the review posted by Rosemary Redfield of the University of British Columbia which very clearly and methodically exposes the shortcomings of the experiments from a microbiology point of view: "Arsenic-associated bacteria (NASA's claims)". She was by no means the only one who raised serious questions soon after NASA's press conference and the publication of the scientific article in Science: Read "Arsenate-based DNA: a big idea with big holes" and "Ordinary evidence would do". The main contentions that have been raised have to do with the controls used in the experiment, the methods of detection of arsenate in DNA and other molecules, and about whether or not the researchers managed to lower the amount of phosphate enough to actually "force" the bacteria to thrive on arsenate instead.

I also concluded that this kind of aftermath is "science as usual", not something to get particularly worked up about, but that the style of communication that drove the story just doesn't allow for this process to come through. We get a mismatch between the communication of science, which affects people's expectations of science, and the actual scientific work method. This story couldn't have been better adapted for fast and enthusiastic dissemination through blogs, Twitter feeds and YouTube channels, but science isn't quite adapted to the internet... yet, and a very interesting conflict arises. A few bloggers have focused on this as well: "Extraordinary claims attract extraordinary blogging" at Byte Size Biology and "Is That Arsenic-Loving Bug — Formerly an Alien — a Dog?" at Wired.

Falsehoods
Some of the words used to describe the findings have been grandiose to say the least. Most reports claimed that these arsenic-thriving bacteria represented some sort of "new life form". NASA claimed that "the fundamental knowledge about what comprises all known life on Earth" has changed, that "the definition of life has just expanded" and that it "will alter biology textbooks and expand the scope of the search for life beyond Earth". Even the competing journal Nature writes in a news report that this finding "is posed to overturn scientists' understanding of the biochemistry of living organisms", even though they also allow for the doubts to be voiced. Among all this hype, it's difficult to separate the actual bigger picture from the falsehoods.

The discovery of arsenic-thriving bacteria (GFAJ-1 from now on) does not expand our definition of life
Simply because biology doesn't yet have a unified working definition of what life is. I suspect it's the wrong kind of question to ask in the first place. Life is diverse even at its most central processes and the best we should try to do is to define the different "solutions" that living organisms have come up with to solve the problems posed by their environments. Within that framework the possibility of an organism that is able to incorporate arsenic into its biomolecules in phosphate-poor environments definitely represents a previously unknown, "new" and exciting solution, but to say that it expands our definition of life supposes there is a definition in the first place. Thinking in terms of solutions rather than a broad all-encompassing definition also gives a better evolutionary perspective; many solutions are shared by a great number of organisms, some are shared by smaller groups - this leads us to talk about the emergence of innovations along evolutionary history rather than about the presence or absence of life's "common denominators". This would have prevented the next falsehood I want to talk about...

GFAJ-1 doesn't represent a "new life form"
The bacterial strain GFAJ-1 could in itself be called a "new" life form, then again so could any species that's never been described before. The word "new" is more misleading than informative. In this case "new life form" is taken to mean either a species that represents a new and unknown group of bacteria, or a whole different form of life altogether; an organism completely unrelated to anything else we know, part of the so-called "shadow biosphere". The authors of the Science study have refuted these possibilities themselves: To identify the type of bacteria they had isolated, they compared the gene sequences from ribosomal subunit genes between GFAJ-1 and many other species of bacteria, and arrive at the conclusion that the arsenic-thriving strain is related to the known genus of salt-loving bacteria Halomonas. The evolutionary tree below is a visualization of the analysis and shows GFAJ-1 within the yellow-marked Halomonas group. In orange you can also see, to take the point further, that good ole E. coli is a close relative.


Ref: Adapted from Wolfe-Simon et. al. (see reference below).

The fact that this comparison of very old and very conserved genes across many bacterial species could even be done highlights the fact that GFAJ-1 does not represent a whole "other" ancestral form of life. They have ribosomes of the same origin as most other life forms on Earth.

Our fundamental knowledge of what comprises life on Earth or of the biochemistry of life hasn't changed
The perspective presented by the authors of the study is that by demonstrating that the incorporation of arsenate into biomolecules is possible in an organism, then there might be organisms that thrive on arsenate instead of phosphate somewhere on Earth, or indeed on different worlds. This somewhat hyperbolic (and it seems unfounded) supposition is what has driven NASA's astrobiology angle. However, what the authors actually claim to have demonstrated is that arsenate incorporation under extreme conditions could have evolved as a secondary solution to the problem of low phosphate availability. That is, "old life" doing something new. Or in the words of George Cody, an expert in "weird life" who also communicated with Carl Zimmer on the arsenic-thriving bacteria:

Philosophically, if it turned out that an organism could use arsenate in place of phosphate, this would not in my opinion rewrite the rules of life as we know it; aside from the hydrolysis issue, arsenate is chemically very similar to phosphate. A careful chemist could likely synthesize DNA oligomers with an arsenate backbone. As I understand it this is precisely why arsenate is a poison. Ultimately, the idea of a shadow biosphere is interesting, but it would have to be demonstrated to be truly distinct from extant b... Read more »

Wolfe-Simon, F., Switzer Blum, J., Kulp, T.R., Gordon, G.W., Hoeft, S.E., Pett-Ridge, J., Stolz, J.F., Webb, S.M., Weber, P.K., Davies, P.C.W., Anbar, A.D., Oremland, R.S. (2010) A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus. Science. info:/10.1126/science.1197258

  • December 3, 2010
  • 06:48 PM
  • 506 views

My summary of NASA's arsenic-thriving bacteria story

by Daniel in Ego sum Daniel

Almost instantly after coming home from work yesterday, I noticed a steady stream of mentions of a mysterious and hugely hyped NASA press conference scheduled for later in the day trickling in via Facebook, Twitter, blogs and news sites. I got excited, but also a bit confused. NASA's announcement seemed spectacular enough:

NASA will hold a news conference at 11 a.m. PST on Thursday, Dec. 2, to discuss an astrobiology finding that will impact the search for evidence of extraterrestrial life.
After much speculation, what we all now know was revealed at the press conference:

Researchers conducting tests in the harsh environment of Mono Lake in California have discovered the first known microorganism on Earth able to thrive and reproduce using the toxic chemical arsenic. The microorganism substitutes arsenic for phosphorus in its cell components.

Source: xkcd. "According to a new paper published in the journal Science, reporters are unable to thrive in an arsenic-rich environment."

A discovery that according to NASA means that "the fundamental knowledge about what comprises all known life on Earth" has changed and that "the definition of life has just expanded". Hyperbolic much? The paper that describes these new findings was published in advance yesterday in Science, find the link at the bottom of the post, and there are indications that associated papers with more details will be published in the coming months.

It's been exciting to follow the reporting pretty much directly as it's happened and I've been Tweeting and Facebooking the story unfolding almost in real time since yesterday. All in all this story has been a great exercise in observing how online science reporting works and how blogs and social media works within this context.

By this time yesterday the furore was on:

Phil Plait's Bad Astronomy blog was very early in giving a measured but enthusiastic summary; "NASA's real news: bacterium on Earth that lives off arsenic!", so enthusiastic that a few errors, now corrected, made their way in. For the best and most sensible summary and background I would point to Carl Zimmer's excellent post "Of Arsenic and Aliens", which was posted simultaneously with NASA's press conference. Soon enough SciTech news sites started picking up the story: WIRED titled its report "NASA Finds New Arsenic-Based Life Form in California". New Scientist sank to new and lower lows with the headline "Arsenic-based bacteria point to new life forms", although they do a good job at presenting the doubts that remain about the finding. The Guardian's science pages started tracking the story pretty soon as well, posting links to the different reports as they were coming in: "Nasa unveils new life form: Bacteria that thrive on arsenic".

The somewhat fallacious tendency to call this a "new life form" becomes really apparent at this point, no doubt fueled by the sensationalistic NASA press conference and its astrobiology angle. Many reports give the impression that the arsenic-thriving bacteria represent some sort of "alternative" branch of life, or a primordially ancient form of life that we weren't aware of, which is incorrect, or that the bacteria were discovered incorporating arsenic into their cellular mechanisms in their natural environment, which is also incorrect.

Here in Sweden the major newspapers also ran spectacular headlines about the "new life form": Dagens Nyheter wrote "New life form discovered in a lake of arsenic", and Svenska Dagbladet followed with the not quite as wrong "The bacteria that lives on arsenic".

An interesting aspect in the stream of information is how the story itself has evolved since the first reports and the press conference. At first it wasn't clear from many reports if they had actually proven that the arsenic-thriving bacteria incorporated arsenic instead of phosphorus into their DNA, and what exactly the evidence was. Some reports presented doubts about the evidence, some didn't, but several have had to append or correct their information. Many still remain tentative about whether or not the evidence is sufficient to claim that arsenic was incorporated into the bacteria's DNA, not to speak of other cellular components that include phosphorus such as the cell membranes and ATP. This is all "science as usual", but the "science-report-by-press-conference" strategy doesn't exacly mirror the long and tentative process of scrutiny that all scientific findings have to go through even after publication.

I think that perhaps our demands for a clear and instant message are too high?

Aside from Carl Zimmer's post, I can recommend the following science blogger's takes on the story: Greg Laden's "NASA's new organism, the meaning of life, and Darwin's Second Theory", which focuses on the evolutionary implications, and PZ Myers' "It's not an arsenic-based life form", which very clearly describes the actual experiments and findings. Ed Yong's "Mono Lake bacteria build their DNA using arsenic (and no, this isn’t about aliens)" also adds some background to the field of study of arsenic-loving microorganisms and warns against going overboard with the conclusions.

Notice how RealScientists(TM) avoid writing about "new life forms".

In the end though, there's no doubt this is an exciting and significant finding, and the reason this will become THE scientific story of 2010, at least attention-wise, is not just because of the shrewd media strategy. Yet I can't help but being a bit cynical about the whole THIS WILL CHANGE EVERYTHING 4-EVER!!!!1 hype, especially since it very easily can lead to widespread misconceptions about biology.

Wolfe-Simon, F., Switzer Blum, J., Kulp, T.R., Gordon, G.W., Hoeft, S.E., Pett-Ridge, J., Stolz, J.F., Webb, S.M., Weber, P.K., Davies, P.C.W., Anbar, A.D., Oremland, R.S. (2010). A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus Science : 10.1126/science.1197258
... Read more »

Wolfe-Simon, F., Switzer Blum, J., Kulp, T.R., Gordon, G.W., Hoeft, S.E., Pett-Ridge, J., Stolz, J.F., Webb, S.M., Weber, P.K., Davies, P.C.W., Anbar, A.D., Oremland, R.S. (2010) A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus. Science. info:/10.1126/science.1197258

  • November 18, 2010
  • 12:51 PM
  • 470 views

Is there anything fish don't do!? Mucus-feeding and prolactin

by Daniel in Ego sum Daniel

Much of my work involves studying fish genomes. Over time I've gotten to know them pretty well and I can only conclude that fish are incredible and inordinately interesting creatures. Unfortunately fish have an undeservedly low standing in the eyes of the general public, as well as many researchers in more mammal-oriented fields, often being referred to as "lower vertebrates" in the great evolutionary story that led to "higher vertebrates" like mammals. In fact, more than half of all vertebrate species are fish, not "higher vertebrates", and fish encompass the great majority of all vertebrate diversity. In most senses fish are the "typical" vertebrates. Their origin set the whole stage for vertebrate development, anatomy and physiology and the fair view of vertebrate evolution should be that reptiles, birds and mammals, basically everything that lives on land, are a subgroup of highly specialized fish, an interesting "side-step" rather than the "crown" of evolution.

So why this preface in defense of fish? I have found a little story that more than anything I've read lately highlights the deep connection between fish and mammals and does a very good job at blurring the distinction between what's considered typically mammal and what fish are capable of. Plus, it relates to my own research.


Discus fish (Symphysodon aequifasciatus). Ref: Flickr.

Behold the discus fish.

The three discus fish species of the Amazon basin in the genus Symphysodon are something out of the ordinary in that they exhibit parental care behaviors and feed their fry with a special mucus secreted from both parents' skin. The fry start nibbling from the parents' skin a few days after hatching and continue for a up to 3 weeks before being "weaned off", in a phenomenon akin to mammal lactation. Not only does the composition of the mucus change as the fry grow in a way that mirrors the changes in the composition of milk in mammals, it also seems that there are shared mechanisms in the stimulation of discus fish mucus production and milk production in mammals. Discus fish are not the only fish species that have these qualities, but they have become the typical example, not least because they have been appreciated as aquarium fish for a long time. You can find and abundance of videos showing discus fish parental behaviors on YouTube.

The composition of non-parental skin mucus and parental skin mucus in discus fish is different. During breeding the mucus contains many antimicrobial proteins and factors that stimulate the regeneration of skin cells; this is to protect the parents from infections due to the fry's excessive nibbling. But the mucus also contains antibodies and factors that are thought to contribute to the fry's immunity during the very first period of life, akin to mammal milk. In another parallel, the levels of antibodies and proteins are at their peek around the time of hatching (birth) and decrease when it's time for "weaning".

In mammals the hormone prolactin, as the name indicates, regulates the production of milk through the prolactin receptors that are expressed on milk gland cells. However prolactin is a very old hormone (fish have prolactin too!) and probably the hormone that has the most known functions in all of endocrinology. In fish it mostly acts on the gills, the intestines and the kidneys to control the regulation of water balance in the body. This is probably one of the original roles of prolactin in the first vertebrates a few hundred million years ago. However, in both mammal and fish, including the discus fish, prolactin has been shown to stimulate parental care indicating that the effect on behavior also is old. Lactation on the other hand seems to be a relatively new function for prolactin and thus the name "promotor of lactation" is a misnomer if there ever was one. Or is it?


Ref: Khong et. al. (see reference below)

Studies of the expression of the prolactin receptor in the discus fish skin reveal that it's expressed in significantly increased numbers during the parental phase, as you can see in the figure above, indicating that it's prolactin that stimulates mucus production! What an incredible parallel! It's the closest thing to breast-feeding fish that you will ever find. The prolactin receptor also seems to mediate the creation of new mucous cells in the skin, further increasing mucus production and counteracting the effects of the fry's nibbling. The mucous cells of the skin are a kind of epithelial cells, so are the milk gland cells in mammals and the sweat gland cells that they share an origin with. So are the cells in the fish intestine and gills that are involved in water balance regulation. Do you see the pattern? Milk secretion, mucus secretion, sweating, the transport of water across a barrier are variants on the same theme.

The similarities between mammal lactation and discus fish parental mucus production could all be incidental, the result of convergent evolution, but the involvement of prolactin receptors in both processes speaks for there being a deep ancestral mechanism shared between lactation in mammals and mucus production in fish.

Buckley, J., Maunder, R., Foey, A., Pearce, J., Val, A., & Sloman, K. (2010). Biparental mucus feeding: a unique example of parental care in an Amazonian cichlid Journal of Experimental Biology, 213 (22), 3787-3795 DOI: 10.1242/jeb.042929

Khong, H., Kuah, M., Jaya-Ram, A., & Shu-Chien, A. (2009). Prolactin receptor mRNA is upregulated in discus fish (Symphysodon aequifasciata) skin during parental phase. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 153 (1), 18-28 DOI: 10.1016/j.cbpb.2009.01.005

... Read more »

Buckley, J., Maunder, R., Foey, A., Pearce, J., Val, A., & Sloman, K. (2010) Biparental mucus feeding: a unique example of parental care in an Amazonian cichlid. Journal of Experimental Biology, 213(22), 3787-3795. DOI: 10.1242/jeb.042929  

Khong, H., Kuah, M., Jaya-Ram, A., & Shu-Chien, A. (2009) Prolactin receptor mRNA is upregulated in discus fish (Symphysodon aequifasciata) skin during parental phase. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 153(1), 18-28. DOI: 10.1016/j.cbpb.2009.01.005  

  • November 7, 2010
  • 06:30 AM
  • 462 views

Just got vaccinated... again

by Daniel in Ego sum Daniel

I chose to get vaccinated for the seasonal flu this year as well! This is my post from last year. I think it's a good idea to get vaccinated, even if you're young and healthy. If nothing else, I'm making it a yearly statement in the face of the anti-vaccination loonies. Last year I got vaccinated for both the seasonal flu and the H1N1 or "swine" flu. Understandably last year's relative hysteria about swine flu is nowhere to be seen this year. But whatever happened after that? Wonder no more, there's an article out in BMC Biology summarizing the development of the H1N1 flu since last year's pandemic.In 2009, the new H1N1 pandemic virus exhibited several features that distinguished it from seasonal influenza: it caused major outbreaks in the northern hemisphere summer and autumn, it quickly dominated over other influenza viruses circulating in humans, and it caused widespread disease because of the lack of significant population immunity, particularly in young people. In 2010, the pandemic virus is behaving more like a seasonal influenza virus in that summer outbreaks have not been seen, it is co-circulating with seasonal A(H3N2) and B viruses, and the intensity of transmission is now lower than in 2009. For these reasons, the World Health Organization (WHO) downgraded its pandemic alert from phase 6 to the post-pandemic phase on 10 August 2010. Fortunately, in contrast to descriptions of the 1918 Spanish influenza pandemic, there has been no apparent change in disease severity over the first 18 months of circulation of this virus.What about vaccination then?Fortunately, our worst fears were not realized in the influenza A (H1N1) 2009 pandemic. However, despite all the advances in technology, surveillance and pandemic planning, the virus spread globally within months, reminding us how difficult it is to control. <...> While some quarters have criticized the response as excessive, it is likely the pandemic would have posed a greater problem in the absence of such interventions.Initial clinical trials demonstrated that the monovalent influenza (H1N1) 2009 vaccine is immunogenic and capable of inducing levels of antibody that are considered protective. There is also evidence that vaccination reduces not only the risk of infection but also subsequent transmission to others. Vaccination remains the single most effective method of protection from influenza.That said, it may still be too early to tell just how effective vaccination against the pandemic virus has been. There are two reasons for this. The first is that the initial roll-out of the vaccine occurred too late to affect the first pandemic wave. <...> It will be interesting to see whether the delay in onset of the influenza season and its relatively low activity is due to the extensive vaccination program. We have to wait and see.The article also details why the susceptibility was so high in young people (lack of immunity), why some people where so severely affected (lack of immunity and lowered inflammatory response), and why the virus spread so fast (large pool of susceptible individuals due to... you guessed it, lack of immunity). Get the picture? Turner, S., Doherty, P., & Kelso, A. (2010). Q&A: H1N1 pandemic influenza - what's new? BMC Biology, 8 (1) DOI: 10.1186/1741-7007-8-130... Read more »

Turner, S., Doherty, P., & Kelso, A. (2010) Q. BMC Biology, 8(1), 130. DOI: 10.1186/1741-7007-8-130  

  • October 21, 2010
  • 02:03 PM
  • 493 views

Einstein's brain

by Daniel in Ego sum Daniel

Einstein's brain was photographed only hours after his death. Ref: Falk (see reference below) Einstein's brain pops up quite often in popular science lore about the relation between brain size and intelligence. The most common myth (based solely on my own experience) is that Einstein's brain was smaller than average ergo brain size has nothing to do with intelligence. In actual fact, the size of Einstein's brain (as measured when retrieved shortly after his death at 76) was completely unremarkable for a male specimen of his age. As it turns out brain size is a lousy correlate of intelligence anyway, regardless of Einstein's brain. In my opinion it's probably only a great correlate of skull size. So it's less about how much you have and more about what you do with it. I usually bring this up when I lecture about the anatomy of the brain.With that in mind, today I came upon a recent commentary on a study of Albert Einstein's brain published in Frontiers in Neuroscience last year. This re-analysis of the surface features of Einstein's cerebral cortex, using tools from the field of paleoanthropology, lead anthropologist Dean Falk to make new observations about Einstein's brain and the relation they might have had to his exceptional capabilities.Falk closely analyzed photographs of Einstein’s brain that were taken within the first few hours of his death. These calibrated photographs, along with direct caliper measurements were the primary materials Falk used to reanalyze Einstein’s brain. Two identifications, a long, unnamed sulcus (u), and a knob (K), are the emphasis of Falk’s research because they are both unusual and uncommon.One of Falk’s most groundbreaking findings is the presence of continuous precentral superior and inferior sulci (pcs and pci). These are present on both right and left hemispheres of Einstein’s brain; symmetry not found in 98% of the 50 hemispheres scored by Ono et al.I've highlighted some of the structures in the image above in yellow since they're not very obvious in the original. Sulci (sing. sulcus) are the grooves in the cerebral surface and gyri (sing. gyrus) are the ridges.This re-analysis also focused on areas that had been studied before. In particular areas on the lateral parietal and temporal lobes that are involved in the understanding and production of language. Einstein's brain has been the object of study for a long time and if you're interested in the history of this research I recommend you read the original article (see reference below). The general conclusion is that Einstein had several rare features that indicate a very special brain development with regard to how several areas around his primary motor and sensory cortex, as well as his lateral parietal and temporal lobes were organized. Einstein’s brain was characterized by an unusual mixture of symmetrical and asymmetrical features. A rare convergence of the postcentral sulcus with the Sylvian fissure occurred bilaterally in Einstein’s brain, which nonetheless manifested a marked degree of asymmetry in the width of the lateral postcentral gyrus that favored the left hemisphere, and a pronounced knob in the right hemisphere. These asymmetries together with an atypical lack of uniformity in the medial and lateral widths of the pre-and post central sulci indicate that the gross anatomy of Albert Einstein’s brain in and around the primary somatosensory and motor cortices was, indeed, unusual.Some of this unusual symmetry, but also the so called "knob" (K), which is on the area controlling the left hand, can possibly be related to Einstein's violin training and musical abilities as they would have required him to increase his dexterity with his left hand as well as his right hand. If this is true, the young Einstein's musical training left a clear mark on his brain. Some of the same features have been observed when studying the brains of musicians. The diverging organization of some of the areas involved in language could be behind Einstein's reported language difficulties - legend says he didn't say a word until the age of four, and then suddenly spoke in full sentences. Other reports say that he would often repeat sentences to himself until the age of seven. What's even more interesting is that they could possibly also be behind his mathematical genius and unique mind. As an adult, Einstein famously observed that ‘the words or the language, as they are written or spoken, do not seem to play any role in my mechanism of thought. The psychical entities which seem to serve as elements in thought are certain signs and more or less clear images which can be ‘voluntarily’ reproduced and combined’. Einstein laughed when informed that many people always think in words, and emphasized that concepts became meaningful for him ‘only through their connection with sense-experiences’.It's thrilling to consider that this may have affected the way Einstein reasoned and the way he saw mathematics and physics problems, although this is of course very speculative. It also tempts the imagination to think that his musical training as a boy might have, in combination, also contributed to his genius by stimulating his synthetic and analytical thinking. Einstein reportedly often played the violin when stuck on a particular problem. In such case, one could defend the argument that geniuses aren't born, but rather made. At the very least, the study of his brain shows the importance of the developmental processes that happen during childhood and youth for the establishment of, possibly exceptional, brain architectures. What you do with your brain during your life probably makes more of a difference than your genes. Like I wrote in the beginning of this post: It's less about how much you have and more about what you do with it. Spicer, K. (2010). An old brain with new tricks Frontiers in Neuroscience, 4 DOI: 10.3389/fnins.2010.00040Falk, D. (2009). New information about Albert Einstein's Brain Frontiers in Evolutionary Neuroscience, 1 DOI: 10.3389/neuro.18.003.2009... Read more »

  • October 13, 2010
  • 02:45 PM
  • 413 views

Babies, balls and creationists

by Daniel in Ego sum Daniel

A recently published study in PNAS explores how small babies relate order and disorder, or entropy, to the different types of things that may cause them. Amazingly, babies as small as 12 months old show some understanding of the difference between the deliberate and goal-directed "agents" that can cause order, such as a person, and those randomly acting inanimate objects that cannot, such as a bouncing ball. This means that we have some sort of general understanding that the way agents act on the world is completely different from the way inanimate objects act on the world from a very early age. Long before we're able to articulate why we would believe such a thing. Read more about the experiments from this summary at Ars Technica: Toddlers recognize entropy from messy bedrooms. The extraordinary thing here is that the authors of the study don't limit themselves to stating this fact regarding the cognitive development of human beings, but weave in several references to creationism in the article. Although the Second Law of Thermodynamics is often understood as stating that isolated systems tend to move from order to disorder in a manner that increases entropy, we frequently encounter cases where an external entity can take a system from relative disorder to order. Most of the time, the entity is an “agent,” meaning a goal-directed actor, and very often that agent is thought of as having intentions to bring order to the system...The second law of thermodynamics often fallaciously used by creationists as an argument against evolution, based exactly on the temptation to think of evolution as a process that "wants to bring order to the system". This inability of imagining evolutionary processes as completely devoid or intentions or goals underlies many misconceptions about evolution. As adults, however, we do not typically see inanimate objects as capable of having such effects. It is highly unlikely that a rolling ball or falling stone could increase the orderliness of a system.Or indeed a tornado in a junkyard, again a creationist fallacy.We would be surprised to see such an event because we normally assume that order arises from the actions of agents, not inanimate objects. <...> Thus, as adults, we appreciate that one major division in the world of causal entities is between those that are generally capable of “reversing local entropy” and those that are not. Having set the stage, the authors deliver their crushing blow. Although previous work has established that adults, infants, and even nonhuman primates are often remarkably accurate at identifying appropriate causal agents, there also appear to be systematic ways in which children and adults are prone to agentic or teleological explanations. For example, 4-y-old children will report that lakes are “for swimming,” or when asked about the origins of animals and people, tend to endorse explanations that include an intentional creator. In addition, cross-cultural work finds striking commonalities in the prevalence of “intelligent design” arguments among children and adults.One explanation for these types of inferences is that, in our everyday experiences, ordered phenomena do tend to result only from other agents. The correlation is simply too strong and salient to ignore. Moreover, it is well known that adults and children often have a difficult time reasoning about randomness and its effects. Thus, in certain situations, we may overextend a causal framework that includes strong connections between agents and order to erroneously see some ordered patterns as intentionally created by an agent, even when the ordered pattern is actually created by an unintentional, inanimate process.(My emphasis.) So the common fallacy of imagining evolution as a directed process is probably a reflection of how we otherwise cognize about agents and their actions on the world. In turn this makes some of us imagine that there must be an agent behind it. Evolution appears as though it is generating order, or "reversing entropy", therefore it is impossible or it must be caused by an intelligent actor with set goals, depending of which particular flavor of creationism/intelligent design you find most appealing. It might be the reason why intelligent design is so tempting to some. The authors of this study have shown that these cognitive processes, that for the most part lead us to make correct assumptions but that can also cause us to "over-interpret" apparent order, arise very early in our development, before many other cognitive abilities. This can be used as an argument for two statements: That these cognitive processes are absolutely central to our way of relating to the world, which makes them difficult to shake. And that the type of arguments used by intelligent design proponents, who presumably are mostly adults, are based on pretty naïve assumptions made by children and not on the type of reasoning adults use. It also pinpoints something many evolutionary biologists have been saying for a while; that thinking correctly about evolution is actually quite difficult and counterintuitive. Newman, G., Keil, F., Kuhlmeier, V., & Wynn, K. (2010). Early understandings of the link between agents and order Proceedings of the National Academy of Sciences, 107 (40), 17140-17145 DOI: 10.1073/pnas.0914056107... Read more »

Newman, G., Keil, F., Kuhlmeier, V., & Wynn, K. (2010) Early understandings of the link between agents and order. Proceedings of the National Academy of Sciences, 107(40), 17140-17145. DOI: 10.1073/pnas.0914056107  

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