Word of the day: Cardiomyocyte

A cardiomyocyte is a heart muscle cell.

Paraphrased from New Scientist, 5 May 2012: After a heart attack, fibroblast cells form scar tissue on the damaged areas, but they don't pump properly like cardiomyocytes. Dzau (Duke University) used a virus to deliver four microRNAs to switch the fibroblasts to cardiomyocytes. Viruses are, more or less, RNA (or DNA) factories. That is, they are much smaller than normal cells, and spend their lives using a host cell's own mechanisms to manufacture more genetic material.  Preferably its own, but with the benefits of modern genetic engineering, clearly they can be taken advantage of for the benefit of the host cell.

microRNA: short strips of RNA that bind to messenger RNA to stop genes being expressed.

It's not clear to me whether this happens at transcription inside the cell nucleus (like epigenetics, but acting on the RNA), or translation (that is, preventing the ribosome properly decoding some of the RNA into proteins outside the cell nucleus. Either way, it's pretty clever to be able to:
a) identify the switches that change a fibroblast to a cardiomyocyte. Possibly just a function of what proteins are expressed at the ribosome
b) engineer a virus so that it expresses the right set of RNA strands to do the trick
c) deliver the virus to just the right cells. 


(I note that there's been another effort to achieve the same outcome - fibroblast to cardiomyocyte - in a completely different way: using stem cells: http://stemcells.nih.gov/info/scireport/chapter9.asp) 



Where did I encounter this word? Yesterday, in that New Scientist (I'm behind in my reading!)


 

wildcats and cows: the manufactured world

Experience with animal husbandry was a significant influence in the ready and rapid acceptance of evolutionary theory when Darwin finally published On The Origin Of Species in 1859.

There has been long centuries of practice in breeding animals, selecting for a given trait (such as placidity) and deselecting for the undesirable. Aggressive cows ended up on the table along with the passive ones, but their genes don't get propagated thorugh breeding stock.

Result: walking larders.  Humans have, over the centuries and millennia, had such an influence on plants and animals that on the one hand as foodstock, the current versions of wheat, cows, and most else, is nothing like the original wild plant or animal - and indeed in many cases the wild original no longer exists.

On the other hand, humans have reduced most dangerous predators to either extinction, isolation, or simply governable.

There's a Scottish wildcat still in existence.  It's actually a local remnant of the European wildcat Felis silvestris silvestris - which was inimical to human activity, and so was hunted down over the centuries. Not to extinction, as it happens, but not for want of trying. The larger ones were killed; only the smaller ones got away. Thus artificial selection over time resulted in a wildcat that was not much bigger than the domestic cat, and often mistaken for one.

These two examples illustrate the push and the pull that humans are exerting on the world's fauna: reducing it to either the manageable or the usable - or, with the destruction of wildlife habitat, the ignored.

Climate change is only one side of the anthropisation of the planet:  the spread of human culture has already massively shifted the world's DNA stock.  Globalisation brings an attendant spread of uniform food habits and farming practices - amd is shifting the balance still further.  To push the world's DNA in a very specific direction - to greater uniformity in that which serves humans, is surely making our biosphere less robust to trauma.  The bee colony collapse disorder will be seen as an archetype for that degradation of biodiversity.  The cause doesn't need to be directly human, but the planetary changes that allow problems to become global has only one cause.

Genetics 001: The basis of heredity

Most discussions of genetics demonstrate that what is known has been discovered through rigorous scientific experimentation and observation.  One good reason is that this field demonstrates more clearly than the study of fossils the evolutionary basis - and common roots - of all life on earth.  I don't plan to go to that level of detail: because anybody who investigates this subject with any sort of rigour would find the evidence clear, logical, and irrefutable.

Most discussions also begin with Mendel's two laws.  Although they are widely known, I'll reproduce them briefly here.  Mendel was a monk (and scientist) whose work on breeding peas was largely ignored in the 19th century, and rediscovered at the start of the 20th.
Mendel's first law: an individual inherits two factors of heredity for each given trait, one from each parent.
Mendel's second law: independent traits assort independently of each other.
From Mendel came the understanding those two factors above can be dominant or recessive - ie the dominant can mask the recessive, although both factors are present in the individual, and inheritable.


Now, a molecular biology overview.

Animals and plants are eukaryotes: each living cell in every organism has a nucleus, which contains the genetic blueprint for the organism.  This is organised as a set of chromosomes, the same number within each species, but differing numbers for different species.

In contrast, Bacteria are prokaryotes, which means a bacterial cell has no compartmentalised nucleus for the storage of genetic material.  Bacteria are single-celled organisms, as are nearly all prokaryotes.  Most eukaryotes are multi-celled organisms, although some are unicellular - amoeba being an example.

(Although it could be said that organisms lacking nuclei are more primitive, Stephen Jay Gould has illustrated that the likes of bacteria are an extraordinarily successful form of life, having eked out more niches on this planet, and over a longer period of time, than anything else.  Moreover, bacteria in total biomass outweigh the total of all eukarytic life.  They are very successful adaptors.)


Chromosomes take the form of DNA (deoxyribose nucleic acid): very lengthy molecules - largely comprising hydrogen, carbon, oxygen and nitrogen - that are typically packed tightly, in a well-structured way.  Much of a cell's metabolism is controlled automatically via the instructions stored in DNA, which are sent out from the nucleus through RNA, and typically executed by the assembly of proteins from the building blocks of amino acids.

Proteins typically act as catalysts: that is, they facilitate chemical reactions without being changed themselves.  Thus, the presence of particular proteins bring about certain reactions that affect metabolism in cells and through the body.

Spaceship Earth-II: the future of Earth's life

"The earth is going to die in 500 million years!" exclaimed my eight-year-old today. And I had to illustrate to her how this is well beyond the span of our existence. Sort of a deanthropocentric exercise in reverse.

But what of it? Fundamentally, we don't like to think that there's nothing left of us - ever. But does that need to be the case? Yes, the sun is growing hotter, but we have hundreds of millions of years of technological advancement before the Earth becomes uninhabitable. And think where we've come in just one hundred years.

Last week, I was talking through a thought experiment with Mark on this topic.

Space is prohibitively large; commuting is not really an option. Even at the speed of light, the nearest star system to our own, Alpha Centauri, would take four years' travel. And it's questionable whether there's anything habitable there. It's a binary (plus) system, and the gravitational flux of two nearby suns may not foster stability.

Further, our bodies evolved in gravity, and it's not clear we'd survive for extended periods in minimal gravity environments.

In Rendezvous With Rama, Arthur C Clarke posited a mammoth cylindrical body 50 kms long, with habitation on the inside. That's an overwhelming construction endeavour. I think there are easier options.


My suggestion is that to travel beyond the Solar System would take far more massive an environment than we could possibly build ourselves. It would be simpler to grab an existing body, and power that away somehow. As Mark pointed out, this is the Space: 1999 scenario, a science fiction series where the moon was torn away from Earth.

Possibilities include using something large from the asteroid belt, a moon from Jupiter or Saturn (such as Ganymede), or maybe something far out, such as that erstwhile planet Pluto.

Issues include heat, propulsion, gravity, retention of atmosphere, and other life-sustaining variables. By the time it's worthwhile thinking about it, I'd say we'd have the technology to allow us a few options.

This is the stuff of science fiction, certainly; plenty of options have already been canvassed in that milieu. Burrowing underground would provide sturdy shelter, although digging enough habitable space would be Herculean. Other options include domes on the surface - or terraforming.


Ah, terraforming. Rather what happened to our own planet. Microbial life has built up our current atmosphere and environment; we're just the evolutionary outcomes that could adjust to it. It took hundreds of millions of years to develop, but I think it's reasonable to anticipate we'll be able to engineer biological solutions that work faster.

However, out beyond the easy reaches of the sun, everything freezes. There would need to be both sufficient gravity to hold an atmosphere (or to be able to continually regenerate it), and heat sources sufficient to prevent that freezing. The latter would be most feasible through nuclear fusion sources - we haven't succeeded at this yet, but I can see no reason it won't come. It's what the sun uses.

Gravity is a matter of using a large enough body. Life on Earth is, of course, evolved for our specific gravity, and much more research is needed to understand how or whether current life forms could adapt to lower gravity, or whether we'd need to engineer alterations that would allow various forms to survive in a somewhat different environment.

Because we would want to take with us as much of the existing variety of life as we could. This could involve storing samples at the DNA level, for later development/unpacking using either technological or substitute development (incubation) methods. In any case, plants and animal life should be considered an essential part of our environment - our being - and taking that with us would not be at issue. Bacteria and viruses too, surprisingly enough. Bacteria are our microbial engineers, a fundamental tool of life. Viruses have helped us become what we are today, though infiltrating our germ lines, they have imparted in us the resilince - and functionality - that we possess today.

The Earth's variety of life evolved specifically because the amount of solar radiation both protects us from other stellar sources, and generates mutation by occasionally knocking around with DNA. Outside Earth's orbit, mutation would happen at a different rate, which we would have to account for. Lesser rates would not be an issue: we are now at the point of engineering our environment to overcome the 'need' for adaptive outcomes of mutation. Greater rates of mutation would necessitate careful screening to optimise outcomes.

Yet that begs the question: outside the Earth's specific environmental womb, would it be more beneficial to engineer adaption in ourselves, so that future generations can make the move more readily? The biggest barrier is ourselves: the fact that we are rather wedded to our current form, no matter how ill-adapted to space journeying. I suspect we would be more willing to put extra effort into optimising our environment, than to force evolutionary change on our own grandchildren.

I have great optimism that we will survive in the long run. Even if, to paraphrase Steve Kilbey, we end up as digital memory*.


None of this is a substitute for getting our own planet in order. But if we can succeed in that, we'll probably be well placed to survive past the use-by date of our planet.


*The Church: Fog, (1992 B-side to Ripple)
It hurts to think that in a hundred years
We'll all just be microfiche
Our names and the names of our songs
Cataloged and filed away

- however, compared to the fate of most of our ancestors, I'd be happy to survive in digital form.

Burning ice: impending danger

Russian permafrost offers up both hope and danger in this warming world.

It is a great preservation medium, not of fossils so much as DNA from unfossilised specimens (with tissue that hasn't degenerated and been replaced by seeping rock). Such finds, unfortunately, would only go back through the last few ice ages, up to about 700,000 years versus 65 million years for the dinosaur extinction.

But there is also a vast store of carbon fuel trapped within the permafrost, in a form known as methane clathrate: molecules of methane trapped within ice crystals. The tone of a recent New Scientist article was thrilled with the possibilities for this potential energy source, but strangely muted about the danger to the planet: it will accelerate global warming on release - methane being far stronger a greenhouse gas than carbon dioxide.

Clathrates are a delicate form of methane: if gas is extracted or gets loose, pressure can destabilise neighbouring crystals for a chain reaction: a "methane burp" that in releasing vast amounts of greenhouse gas, can also generate landslides and tsunamis.

There are three possible eventualities: permafrost clethrates are released as the planet warms, the deposits are exploited for fuel, or they stay in the ground. Perversely, if the planet warms and they are to be released anyway, it's better to use the fuel. On the one hand, methane molecules warm the atmosphere at 20 times the rate of carbon dioxide molecules. On the other hand, burning methane generates only half as much carbon dioxide as burning coal.

Therein lies the reason for the article's gleeful tone. We should be restructuring away from fossil fuels, but if the planet warms as expected, the methane gets released anyway.

You can read the full article here. Unfortunately it doesn't include the photos of burning ice from the print version. Spectacular - but deadly.


Whether or not extraction takes place depends on whether our energy and environment plans are fully evolved by the time extraction becomes fully viable. Will the burp happen anyway by now? The odds are not good.

Your ancestor is not your ancestor

It's easy to envisage a brave new world of healthcare, where your genetic makeup can be interpreted in minutiae, and therapy developed that is fine-tuned to your specific needs. The genetic information would be supplemented with reference to detailed ancestral information - for those with extensive enough family trees.

I heard something in passing on the radio a few days ago, which gave that a reality check. I think the woman being interviewed was a geneticist, who had researched the relationship between genetic and genealogical information - that is, comparing DNA information with supplied family trees.

Of course, the result should be quite obvious. She couched it in terms of paternity, but it turned out that there was substantial disconnect between the two sources of information. In effect, there were too many cases where the attributed father was not the actual father. This would happen for any number of reasons, from infidelity to retro-fitting a respectable background.

I see some irony here, for the many people who, for example, would like to trace their roots back to royalty. Apart from the fact that most English people (all?) should share some royal blood if they go back far enough, red herrings would abound. On the one hand, there would be cases like my grandmother's family, where it's plausible that purported links to the Dukes of Bedford would be simply an attempt to increase cachet.

Yet on the other hand there would be the hidden stories that may reveal closer links to a royal family than expected. Hidden for as many reasons as there are players.

I would not be surprised if the information flow ended up being in the converse direction. Genetic analysis may be able to correct family trees.

In that light, there is yet hope for genealogists. However, for that level of detail I would not be holding my breath. It is unlikely to come soon.

Death of the Gene pt 2 (what is a gene? pt 397)

Following on from yesterday is yet another discussion on the Gene. This constitutes a brief overview of the article Genomics Confounds Gene Classification (Michael Serenghaus and Mark Gerstein), from American Scientist (Nov 2008).

The article clarifies the concept of a gene by rendering it more complex. Which sounds somewhat perverse, but the notion of a gene has always been rubbery, possibly due to efforts to render simple something that is more complicated than taxonomically-inclined people would like to deal with.

Quickly recapping, the human genome consists of 23 pairs of chromosomes located in the nucleus of nearly every human cell. Those chromosomes - long strands of DNA - contain some three billion items of information. A sequence thereof is used to build up proteins which are the biochemical fundaments of metabolism and life. Thus comes the concept of "one gene - one protein" - that the most atomic process constitutes the encoding of a protein, which ultimately determines a human characteristic, and is thus a "basic unit of heredity".

Via Wikipedia comes the claim that there are an estimated 20,000 to 25,000 "protein-coding genes" in the human genome; the Wikipedia collaborators thus nail down the Gene between the articles on Human genome and Gene. This leaves a number of troubling questions, however, including the function of large swathes of the genome - (only) some of which may be "junk DNA" and may have been inserted by viruses into germ line cells (thus fostering inheritance).


Seringhaus and Gerstein's central premise is that the gene, as "biology's basic unit", is "not nearly so uniform nor as discrete as once was thought" - so "biologists must adapt their methods of classifying genes and their products".

Part of the problem is that the encoding process is more complicated than simply reading a contiguous strand of DNA data. That has been recognised already by conceptualising introns, segments of data that are removed from the ultimate coding process (both main strands of theory posits these as junk). There are also control sequences that govern, inter alia, the beginning and end of the transcription process. However, the overall coding process has been found to involve serious convolutions of the DNA strand. Transcription is not purely a sequential process: exons (coding strands) are non-adjacent and "important control regions can occur tens of thousands of nucleotide pairs away from the targeted coding region - with uninvolved genes sometimes postioned in between"... "the physical qualities of DNA, its ability to loop and bend, bring distand regulatory components close".

The other complication is over functionality of a "gene". Seringhaus and Gerstein: "Function in the genetic sense initially was inferred from the phenotypic effects of genes... but a phenotypic effect doesn't capture function on the molecular level. To really elucidate the importance of a gene, it's vital to understand the detailed biochemistry of its products." But each protein, each enzyme, can have a variety of biochemical effects. "Deciding which qualities of a gene and its products to record, report and classify is not trivial". This leads to the system of classification called Gene Ontology (GO). Much more complicated than a simple hierarchy, it uses a Directed Acyclic Graph structure, where each node can have multiple parents - resulting in a rather messy-looking chart of interconnected notes. This, and the "flood of new genomic data" mean a "large volume of data" which can "paralyze the most dedicated team. Precisely this problem is occurring in biology today".

The solution may be found in the semantic web project mentioned yesterday, where indefinite amounts of information and, importantly, relationships, can be stored. Simplicity vanishes, but information can be retained in toto, and compiled collaboratively that can be mined for meaning. And intuitively, such complexity makes more sense.

The Semantic Web (Death of the Gene, part 1)

Two recent articles - in American Scientist and New Scientist - purport to sound the death knell of our understanding of genetics. Interestingly enough, the New Scientist article is the more sensationalist, whereas American Scientist has the more meaningful one.

First, however, a diversion into computer science.

I first encountered the concept of the Semantic Web about four years ago, through a seminar presented by the W3 Consortium. The Semantic Web was envisaged as a successor to the worldwide web, something to better enable collaboration.

Web pages, written in Hypertext Markup Language, represent a rather unstructured way to navigate information. True enough, linkages are made from one concept to another. But on the whole the effect is a rather unstructured journey, with no instrinic meaning underpinning one's meanderings.

In contrast, the Semantic Web is intended to be a network of information in which the navigational links are imbued with specifically defined relationships, such that they could be machine-read. Web pioneer Tim Berners-Lee has referred to this as a Global Giant Graph in contrast to the worldwide web. Descriptive relationships are facilitated by languages designed for depicting data: Resource Description Framework, Web Ontology Language (OWL), and particularly XML (Extensible Markup Language), which is already in heavy use for defining data in a very wide range of contexts.

Why do this?, was the question that occurred to me at that seminar. The applications proposed were restricted to scientific fields such as pharmaceutics and bibliographics, somewhat esoteric to me.

But this set of design and representational principles is starting to make sense in fields in which collaboration is necessary simply because it is too difficult to keep track of a field that is constantly burgeoning, updating faster than any traditional publishing method, and too large for any one person or group to maintain. Thus, an ontology: precise specifications for a knowledge-classification system.

That could easily be a description of Wikipedia. Such an endeavour is not possible without the web, simply because it calls for such a vast community of contributors.

The same could apply to a more structured discipline, where structured relationships may be just as important as the single instance or 'article'. The ensuing structures, spread out over a large number of web sites, could then be data-mined for meaning.

There is increasing need for this in genetics, as we start to see the concept of a gene break down, and the need to build a large number of relationships out of a genetic code with billions of letters.

Reversing extinction via DNA

A recent study published in PNAS reported that mice had been cloned from frozen DNA (journal abstract here; press report here). This had been thought impossible: that cellular ice crystals would destroy the DNA.

This does not constitute a universal panacea for recovering extinct species, but it has implications for DNA recovered from unfossilised remains recovered from permanently frozen locations, especially Antarctica, Canada, and Russia.

There would remain a number of scientific hurdles, including incubation, but the puzzle pieces are starting to fall into place. Yet there are a couple of ominous tones in this news.

First, we may be running out of time. Permafrost regions have begun thawing already. (And this is a double-edged sword: on the one hand, it will make scientific discovery easier for a period of time, but on the other hand, it will likely hasten the warming process as masses of organic matter will also thaw, rot, and release more atmospheric carbon to hasten the warming process.)

Second, it would be tragic if scientific progress bred complacency towards looming extinctions. Prevention - preserving whole ecosystems - would be so much easier and less fraught than attempting to recreate the systems. But our form of democracy is traditionally geared to the dissonance of desiring an outcome but not making the hard decisions. A recipe for complacency.

The DNA of NY air

A bloke is sampling New York's air to extract the DNA from its microbes.

A 'microbe' is a rather generic term for a microscopic organism. The sample would encompass bacteria and fungal spores in particular, as well as a few other stray strands. Report here.

The scientist is Craig Ventner, who competed against the publicly funded project to sequence the human genome. He states that only about 1% of the organic matter in the air could be cultivated in a laboratory.

A fascinating experiment for one of the most urban centres in the world. Most of the answers would veer into the mundane, but there may be a few surprises, particularly for bacterial DNA, where mutation can be rapid relative to large-scale organisms.

Ventner has apparently uncovered about a million new "genes" from a similar exercise run in the Sargasso Sea (a mass of seaweed in the middle of the Atlantic). That's not too surprising: it is a unique ecosystem. The NY experiment is unlikely to be as productive, but it strikes me as a useful mission.

The role of the virus in evolution, part 2

To summarise:
Viruses have a wide variety of forms and actions. For just about every type of organism from animals to plants to bacteria, there are viruses that infiltrate them. Some viruses attack a broad range of cells; some are specific to specific kinds of cells: tissue tropism defines the set of cells/tissues that a given virus attacks.

Some viruses attack germline cells (those involved in reproduction); some of those (endogenous retroviruses) can insert their own DNA into the germline cell's DNA, which means some viral DNA can end up getting passed on to subsequent generations by the host organism.



Thus we have Human Endogenous Retroviruses (HERVs). The end results could be quite varied. It's feasible that this is the source of much junk DNA (that is, DNA which doesn't fulfill any [known] function in the developmental process). Yet that inserted DNA could be harmful: HERVs are suspected of involvement in a range of auto-immune diseases, including multiple sclerosis.

On the other hand, the recent New Scientist article on viruses (here, called in the print version Welcome to the virosphere) suggests ERVs have also played a crucial positive role in the human immune system's ability to respond to viruses never encountered before.

And HERVs have been linked to gene regulatory networks, which determine which genes are activated and deactivated. Thus they appear to be a key enabler of evolutionary change: "the main difference between closely related species is not in genes themselves, but how they are expressed" (ie whether and when they are activated).

Patrick Forterre, of Paris-Sud University, has been studying DNA mechanisms since the 1970s. His analysis of DNA across the three domains (bacteria, archaea, and eukaryotes [organisms with cellular nuclei, ie most of us]), found disparate DNA-related connections across each pair of domains that weren't present in the other. His ultimate conclusion (see this PNAS article for some of the detail) is that at an early point in the evolution of life there was "a period of wild biochemical experimentation"; innovative mechanisms were shared between different life forms through gene transfer by viruses. Forterre posits numerous alternative life systems, of which all that is left is the three domains, plus remnants of the rest surviving in the virosphere. Given that viruses are more abundant than any other organisms, and gene flow is greatest via viruses, "it should not be a surprise that major innovations could have occurred first in the viral world, before being transferred to cells".

In effect, viruses have been "sharing the successful [biochemical] experiments" - those mechanisms that survived in the DNA being the successful ones. Forterre goes further and credits viruses for many leaps in complexity of life, including development of DNA from RNA, and the key innovation of cell nuclei.

Ultimately, the NS article concludes that as species, we are "leaky vessels" of DNA, and that the biosphere can be seen as one "interconnected network of continuously circulating genes - a pangenome".

The evolutionary significance of viruses, pt 1

The DNA that makes up the human genome is the blueprint for the biochemical processes that constitute the embryonic development of humans. That's all that is really needed: a recipe for the step-by-step development of a baby. The DNA is a long chain of instructions for the creation of proteins that, in the right order, conduct the chemical processes.

And that human genome contains a lot of DNA that came from viruses.

There's debate about whether viruses are 'living' - but at one level, that's just semantics. They are organisms that cannot survive outside a host, and consist of little beyond a strand of DNA (or RNA) and the mechanism to breach a host cell and use the host to help replicate the genetic material.

Retroviruses are so called because their genome is RNA, and they use a reverse transcription process to make DNA equivalents of that RNA. That DNA can end up being integrated into the host cell's DNA (with the help of an integrase enzyme).

That in itself would have no evolutionary significance, except that it's possible for that DNA integation to happen in any germline cells - that is, one of a successive set of cells that would ultimately create the sperm and egg cells. If so integrated, the inserted DNA would then become inherited.

This is the endogenous retrovirus, ERV, and according to a recent New Scientist article, 8% of the human genome clearly comes from that source, and over 50% probably does.

Evolution: Bacterial DNA exchange

DNA refers to complex molecules that contain genetic data for all living organisms. The most commonly understood locus for that data is the genomic DNA in the nucleus of each cell in an organism - or in the nucleoid (a somewhat nucleus-like region), in the case of prokaryotes (less complex, mostly single-celled organisms that lack a nucleus per se).

There are various other loci for that genetic data, beyond the core genomic DNA in cell nuclei - for example, mitochondria, viruses and plasmids, for example.

DNA is typically transmitted direct by direct inheritance, sexual reproduction in most more complex organisms, binary fission in more elemental organisms such as bacteria. Yet we see evidence that as well as that "vertical" data transmission, some "horizontal" exchange of genetic data takes place. I noted here that Bdelloid rotifers somehow acquire DNA from a number of sources outside the species.


Bacteria apparently exchange DNA too. A recent paper in the journal Science discusses this (also reported in New Scientist). Two species of bacteria, Campylobacter jejuni and Campylobacter coli, share about 87% of their genetic material, suggesting they diverged about 100 million years ago (by contrast, humans and chimpanzees share about 94%, having diverged about 6 million years ago). These bacterial species don't normally run into each other in the wild, as they inhabit different animals. But the artificial environment of farms has brought their environmental niches together, where they have both been able to infect chickens and cattle.

Samuel Shepherd and colleagues from Oxford University found one variety of C. coli was carrying more genes from C. jejuni than others studied; in nearly all cases, the genetic sequence in question was unchanged between species. This suggested they were exchanging DNA recently; the scientists' analysis indicated they were converging more quickly than mutation was diverging them.

This is said to be the first concrete evidence that speciation of bacteria is affected by environment in a similar fashion to more complex animals. I find it very surprising that it is a first; intuitively, it makes good sense that environment influences evolution in bacteria just as much as in other living things.

Further, I would be very reluctant to call this species convergence, as the report's authors do. The bacteria's genetic driftage would be a trend, but it would be hard to call it an absolute. I reckon it would be particularly unlikely for species to perfectly converge such that their genetic material is cleanly lined up identically at all points. I'm happy to be proven wrong, but I don't think this will happen. I would posit a randomness to the exchange, similar to the randomness of mutation. (However, at this stage we don't know the speed of the exchange: whether environment or proximity can hasten it to the point of a blur.)


Aside from the exchange of genetic material, the article makes the point that there remains disagreement over the nature of speciation in bacteria, and how the boundaries of species are maintained. My understanding of this issue would related to the nature of species stability in more complex organisms: the fact that sexual reproduction necessitates an exchange of genetic material at each generation would inherently stabilise species, whereas surely binary fission would normally destabilise. Mutations in sexual reproduction have only a 50% chance of being carried forwards, whereas in binary fission (perfect replication or no), any mutations are carried forward at each generation.

So why would bacterial species ever maintain stability? Two possibilities are the DNA exchange mechanism (a stabiliser in the immediate term), and environmental factors over the longer term.


All this is a mere curtain raiser for the role in DNA propagation of... viruses.

Evolution: birds re-sorted

A recent analysis of bird DNA has reported some corrections to the phylogenetic family tree. The study, published in the journal Science, looks to be an equal collaboration between a scientists from a number of American universities.

They report corroborating some contentions groupings (eg flamingos and grebes), and making some surprising new groupings (eg hummingbirds with nighthawks). Some conceptual rearrangements were called for too, for example regarding flight vs flightlessness and nocturnal vs diurnal traits.

New Scientist reports some comments on the study indicating some of the findings are disputed. One, for example, places the flying order tinamous right in the middle of ratites, which comprise the majority of well-known flightless birds, including emus, kiwis, ostriches and moas.

Tinamus major

Tinamous and ratites had already been nestled together in a superorder called Palaeognathae, whereas all other birds are grouped as Neognathae. The fossil record of tinamous, from South America, is poor, only going back 10 million years where the ratites go back to the cretaceous, over 65 million years ago.

Palaeognathae were thought to originate in the southern Gondwana continent. However, more recent DNA analysis, although confirming the monophyly of ratites, appears to show they diverged to recently to share a single Gondwanan ancestor (see discussion here). According to Colin Tudge (The Variety Of Life), a hallmark of the ratites is a lack of deep keel on the breastbone for flight muscles, so including amongst them a flying bird might be unexpected. In fact, most species of tinamous are poor flyers.

These facts in themselves are suggestive that tinamous had, to some extent, re-evolved flight. This would not be out of keeping with the length of lineage of the Palaeognathae.

As I said, the findings haven't met with universal agreement. The study was based on 19 regions of the bird genome, covering 32,000 DNA letters. I'm not qualified to comment on whether this covers sufficient ground, but disagreement on some of the findings would surely revolve around this issue.


Regardless, we should not be surprised to find DNA analysis forcing changes to phylogenetic trees. This has been the exception rather than the rule. We move from systematics predicated on apparent equation of form to that based on the genetic blueprints. The failings of form-based systematics remind us constantly of convergent evolution: that given enough time, the evolutionary path of different animals in similar environments has followed similar paths. The randomness of genetic change provides the differences, but environment trumps that chaos, and steers.

Bacteria directing the course of life?

"Gut bugs may have guided the evolution of life" screams the headline in the New Scientist.

The article reports on a study by Jeff Gordon and Ruth Ley of Washington University in St Louis and published in the journal Science. The microbiologists analysed bacteria from the digestive systems of numerous mammals, then compared the samples with DNA proximity of the animals.

Surprise, surprise, they found that the closer the mammals were genetically, the closer the correlation between populations of gut bacteria.

The scientists speculate that the partnerships between bacteria and mammals could help explain the success in spread and diversity of mammals [over the 65 million years since the KT event gave us breathing space over the dinosaurs]. They say that any adjustments in diet (eg carnivorous to herbivorous to grass-based) would need to be accompanied by a change in internal bacterial populations.


I'm not convinced that this is saying much that is new and significant. That team was caught struggling with the question of causality - did a change in diet to the herbivorous necessitate a change in digestive bacteria, or did a change in internal bacterial populations enable a change in diet?


In fact, evolutionary reliance on useful bacteria is not an unusual phenomenon - quite the reverse. From insects to mammals to legumes, plants and animals have relied on bacteria to aid in essential living processes. For example, Richard Dawkins (Ancestor's Tale) recounts how some (but not all) termites do not - cannot - digest wood fibre (cellulose) unaided, and use internal bacteria to break it down into useful chemicals - the bacteria's waste products. There are several unusual aspects of that bacteria, Mixotricha Paradoxa, but suffice it to say it is found nowhere but in the gut of Darwin's Termite.

This suggests coevolution of bacteria and "higher" organisms can happen in strong partnership, with each essential to the other. In fact, it is simpler and more meaningful to conceptualise bacteria - and the toolkits they bring with them, including the capacity to evolve comparatively rapidly - as an inherent part of the environmental niche in which organisms evolve. Thus our evolutionary environment is both external and internal to us.

Again, there is nothing new in this. But in a built world in which humans usually respond to bacteria as inimical to life, it is another obligation of deanthropocentrism to reorient our thinking to regard bacterial life on the whole as fully essential to where we came from and to our continued existence.

DNA coding - message in a bottle?

"DNA's performance as an archival medium is spectacular. In its capacity to preserve a message, it far outdoes tablets of stone. Cows and pea plants... have an almost identical gene called the histone h4 gene. The DNA text is 306 characters long... cows and peas differ from each other in only two characters out of these 306... fossil evidence suggests [their common ancestor] was somewhere between 1,000 and 2,000 million years ago... Letters carved on gravestones become unreadable in mere hundreds of years”

- Richard Dawkins, The Blind Watchmaker (p123).


The implications, at first glance, are quite spectacular too. For example, why not preserve meaningful information in such a fashion? We send out signals seeking contact with extra-solar civilisation; why not inscribe similar messages in DNA to likewise reach across the distance of time? The human genome, for one, is several billion base pairs long, plenty of space for encoding information that can be read as clear messages.



There are in fact several reasons why this is somewhat impractical.

First, we are already halfway through the effective life-supporting span of the solar system. If, for example, we were to take to the extreme this current artificially-induced extinction event (global warming and destruction of biodiversity), we may leave few species behind; humans would not ipso facto be the most robust of them. If we were to propel destruction back to the bacterial level, there could well evolve again life forms sufficiently complex to analyse and read such messages – but the timing would be quite fine. The gap between “Oh, someone's encoded a message for us in DNA” and the sun expanding to render the planet uninhabitable, could be so small that contingency might not allow for that rediscovery. A simple event on the scale of the KT event's meteorite can play havoc with such timing.

Second comes the inevitable problem with seeking to encode for two different – potentially conflicting meanings. (This is why database designers tend to create primary keys that are independent of specific data fields.) On the one hand, it would be tricky to code a section of DNA to be meaningful both genetically and as a message. And there is no guarantee that such genes would not be subject to evolutionary changes that obliterate the message.

On the other hand, large sections of genome are seen as “junk DNA”, that is, likely to be filling no purpose directly relevant to an organisms makeup. (which is not to say junk DNA is fully useless – for any organism to carry any excess baggage, there is a cost. We just don't know for sure the purpose and origin of junk DNA. It seems to consist of duplicates and misprints of DNA present elsewhere, rather like a computer's waste bin that hasn't been cleared.)

However, junk DNA looks to be more susceptible to mutation than purposive genetic material. Why? If mutation is steady and equally likely throughout the genome (say, for instance, that solar radiation causes a slow but steady rate of damage – a small percentage of miscoding – in haploid genetic material), DNA that has purpose is more subject to error-correction – via the decrease in viability of mutated, ie DNA-damaged, individuals. Thus junk DNA mutation – coding errors – at the individual level is more readily retained, and the information inherent in that junk code would change more frequently. An ideal vacant repository for information, but not as secure.

So a genetic designer could conceivably store non-core information in DNA, but couldn't reliably expect it to last through an evolutionary time scale. However, I can picture the technology being developed to enable insertion of signature or copyright information in junk DNA that would last the required human timeframe.






References

Dawkins, R (1986): The Blind Watchmaker. Penguin, London.

Evolution: DNA part 2: DNA exchange at the periphery

As mentioned before, human DNA is the familiar double helix shape, wrapped up inside the nucleus of each cell. The physical molecule is referred to as DNA; packaged up (with proteins) it constitutes a chromosome; normal human cells have 23 pairs of chromosomes. Each DNA molecule contains a number of base pairs (the unit of genetic information, somewhat akin to a byte in digital information). The human genome of 46 chromosomes has about three billion base pairs.

But the narrative is not nearly as neat as that. We have to understand bacterial DNA, mitochondrial DNA, plasmids, and how they all interact and exchange information.

The basics of human genetic inheritance are relatively simple: sex-specific cells, the sperm and egg gametes, are haploid, only containing one copy of each chromosome pair, pending unification which results in the full complement.

Mitochondrial DNA is one of the complications. This is not a part the human genome located in the nucleus: it's genetic information located in mitochondria, cell elements outside the nucleus that generate chemical energy for the cell to operate. Each cell can contain from one to thousands of mitochondria, depending on the organism type and cell type. When gametes unite, the sperm's mitochondrial DNA is tagged for deletion, so allowing mtDNA to be a marker of matrilineal descent.

Mitochondrial DNA is small (in the order of 15,000 base pairs) and circular - which is pretty much the description of bacterial DNA. In fact, it is generally agreed that mitochondria are bacterial in origin, once endosymbiotic - that is, symbiants located inside the cell that came to be part of the cell's structure. How? A somewhat harder question to answer.

Bacteria are prokaryotic - that is, they lack a cell nucleus. Their DNA consists of a single continous loop. But bacteria, too, have strands of DNA that are separate from their chromosomes. These are called plasmids, rings of DNA that are capable of reproducing independently of bacterial reproduction. Plasmids could be seen as independent symbiotic life-forms in bacteria, similar to viruses except more useful, for example conveying antibiotic res

Bacteria reproduce through binary fusion: that is, they divide into two daughter cells. In the process, the bacterial chromosome is duplicated, one copy for each daughter.

This inheritance mechanism sounds simple, as if each bacterium could be uniquely traced to an ancestor. However, there is an additional mechanism for DNA change: horizontal gene transfer (HGT).

HGT can be seen as a counterpoint to inheritance mechanisms, which could be called vertical gene transfer. HGT, as the name suggests, involves the transfer of genetic information between organisms. This too can result in the spreading of drug resistance - in fact, this was how it was first noted, as far back as 1959. There are three mechanisms for this: transformation involves the absorption of foreign DNA; transduction occurs when a bacterial virus transfers genetic information from one bacterium to another; and in bacterial conjugation, bacteria that are touching can under certain circumstances exchange DNA.

HGT is common in prokaryotic bacteria, and even happens in some unicellular eukaryotes. It would be harder to say that this mechanism impacts on multicellular eukaryotes (having cells with nuclei), the evidence does suggest this has happened. It is suggested that this would have happened in the early stages of eukaryotic evolution.

However, this story is not complete. I noted in May a study of bdelloid rotifers (small marine animals), which found they had absorbed genetic material from a wide range of organisms: animals, plants, fungi and bacteria. The mechanism is not well understood, but it must have been relatively recently in evolutionary terms - in the order of tens of millions of years, maybe.


There are a number of gaps which need explaining, in particular how these mechanisms take place, and how they evolve. I hope to fill in some of the gaps in time, as far as scientific research and my learning permit.

So it would seem that bacteria play an important role in the spreading and exchanging of genetic information - even as far as humans.

Evolution: DNA basics

It's been difficult to grasp the subtleties of some of the discourses on evolution without having a precise grasp of genetic biology. A general understanding can only help so far. In fact, I've found that some of the reason for my difficulties has been that much of the terminology has been used quite loosely, particularly when discussion escapes into the realms of mass communication such as journalism. In particular, the term 'gene' has been tossed about with such reckless abandon that it's all but lost useful meaning in the popular press.

Ideally, Wikipedia would always be a clarifying resource, but I've found that it's often not as clear as one might expect. In days to come, I hope to nail down some basics, starting with DNA.


Deconstructing the term DNA
Schematically, the shape of Deoxyribonucleic acid is the well-known double helix. To be literal, the name is broken down thus. An Acid by definition has hydrogen ion activity greater than that of pure water - this corresponds to a pH of less than 7 (which is neutral). Nucleic acid - mostly either DNA or RNA - is typically located within a cell's nucleus, although there are exceptions. The ribose part of the name refers to the backbone spirals - they are made of repeating groups called nucleotides, each of which is built on a nitrogen base, a phosphate, and ribose sugar. Further, in DNA the ribose sugar has an oxygen atom removed, thus the sugar is effectively deoxyribose.

These molecules are long - about 1.8 metres in humans! - but 46 of them are wrapped into each cell nucleus in our body - these are the 23 pairs of chromosomes.

The two spirals of repeating nucleotides are just infrastructure. The true value lies in the rung that connect one nucleotide to its opposite. Each nucleotide contains one of four bases, at their simplest C, G, A and T. They are paired (via hydrogen bonds) with their opposite number in one of four combinations: C with G, G with C, A with T, and T with A. There are up to 220 million of these base pairs in a human chromosome. Three base pairs in a row, called a codon, provides the blueprint for an amino acid, the building block of a protein. One codon sequence denotes the end of the DNA strand. (There are 64 possible codon sequences but only 20 amino acids, so some redundancy exists in ways of describing them.) A somewhat involved process uses the whole sequence in the manufacture of proteins, which are ultimately responsible for the development of an organism.

Before a cell divides, the two arms of the spiral separate and unwind. This requires the DNA molecule to spin at several hundred turns per second. I can't say my reading has given me a clear understanding of this process, although DNA molecules are located in specific areas of the cell nucleus, so there's unlikely to be any entanglement (and thus interference) between the different strands of DNA in a cell.

Junk DNA
Better described as non-coding DNA, this term refers to coding sections of DNA for which no function has been detected. This currently constitutes about 80% to 90% of the information stored in DNA. There's a variety of thoughts on the reason for this non-coding information. Most of it may be repetitive elements. A lot of it may be historical artifacts of evolution. It's plausible that the function of some of these sequences simply remains to be discovered. Some consider the sequences as stored away for potential future use. This is an interesting puzzle that may speak volumes on evolutionary processes. The evolutionary narrative finds demonstrated that redundant features of an organism don't tend to survive too long: carrying extra baggage costs, and the mutations that ditch unneeded baggage tend to be more successful. Either this precept doesn't apply at the DNA level, or there is some evolutionary benefit in this "junk" being maintained, which we just haven't yet fathomed.

There is some to suggest organisms habitually absorb DNA from other sources (as seen recently, bdelloid rotifers seem particularly good at this), although it's hard to say what part this plays in the mystery.

Other DNA
Mitochondrial DNA is that located outside the cell nucleus, in an organelle (an organ of the cell) called mitochondria, which are used to produce energy. This DNA is circular in shape, as is that of bacteria. In fact, it's thought that it originated from bacteria absorbed by eukaryotic cells. mDNA is inherited entirely matrilinearly; it has been found that mDNA in sperm cells have been marked for deletion. There are hundreds to thousands of copies per human cell, each with around 16,000 base pairs, which correspond to the same set of functions in most higher organisms.



References
Jones, S & Van Loon B (1993): Genetics For Beginners. Icon, Cambridge.
Lafferty P & Rowe J (eds, 1994): The Hutchinson Dictionary Of Science. Helicon, Oxford. [of the sources, this one has proved the most lucid, despite the brevity.]
Wikipedia: DNA, Base Pairs, Junk DNA and Mitochondrial DNA.

New results on relationships of phyla

Paleoblog reports on a Science paper that contends relationships between some of the major animal phyla (body types).

Amongst other results are:
- hypothesising a clade of moulting animals (previously defined as Ecdysozoa;
- relating lophophorates (three small marine phyla) to annelids and molluscs
- molecular confirmation of the monophyly of molluscs;
- supporting velvet worms rather than tardigrades as closes phylum to arthropods;
- hypothesising a clade uniting annelids, brachiopods, nemerteans and phoronids (mainly small marine phyla);
- ctenophores (comb jellyfish) as the earliest diverging multicellular animal of existing phyla.

This last result I find most interesting - that ctenophores diverged earlier than sponges, which were arguably closest in broad morphology to the ediacarans that preceded the Cambrian era from which emerged modern phyla. This newly attributed status of the comb jellyfish has filtered through to reportage in the mainstream press.

The authors analyse about 40 Mb of "expressed sequencing tags" from 21 phyla, including 11 for which the data had not previously been available. This is a form of molecular (genetic) analysis.

The pedigree of the sources is good. I am not sufficiently knowledgeable about the science, so I can only report the findings. There's a lot to digest.

Evolution: Non-directional (The Hox Gene, part 1)

One of Gould's recurrent themes is that evolution is not necessarily a process of increasing complexity. Parasites present a useful example of this. It's all about streamlining.

Gould: parasites "often adapt to their surroundings by evolving an extremely simplified anatomy, sometimes little more than a glob of absorptive and reproductive tissue".


Protozoa are mobile, single-cellular animals. Metazoa are complex, multicellular animals.

Then there are Mesozoa - literally, "middle animals". The major group, Dicyemida, are parasites residing in squids and octopuses.

They comprise one central cell, with about 10 to 40 cells arranged in an outer layer. The debate around these animals had been where to place them in the evolutionary map. A 1999 article in Nature (Kobayashi et al) announced the discovery within them of a Hox gene. These are known only in higher order metazoa, specifically those with three cell layers (triploblasts - they include an inner body cavity).


Thus it has been concluded that these creatures evolved to the most efficient design necessary to survive in that environmental niche. Evolution is about developing the best fit to environment. At times, that constitutes an "arms race" between species; other times it involves a paring back.

Survival is what counts, not persistently marching up a metaphorical hill. The metaphor is more akin to negotiating an endless, multi-path maze. There are many directions that work, some are dead ends, and sometimes there's a park bench to rest at - there's no specific goal other than to be.


Reference
Gould, SJ (2002): I Have Landed; Jonathan Cape, London.