Word of the day: Microbiome

This is clearly a portmanteau word: microbe + genome. Microbe refers to microscopic organisms - in this case, bacteria; genome refers to the sum total of genetic material in an organism.

There's a community of bacteria living within humans that performs functions essential for human life. Scientific American (Mar-2012) says there's at least 10 times as many bacteria cells as human cells in the human body (but those bacteria are a whole lot smaller, with much, much simpler genome).

So microbiome is the genetic material of the [useful] bacteria in the human body. In such a situation, it differs from human to human, so things like this are usually measured on a sampling basis.

According to that Scientific American article (Backseat Drivers, p11), the sum total of all genetic material housed in a human body is then called the hologenome.


Small bone to pick here. The human genome is generally thought of as referring to the genetic material (23 chromosomes of DNA) housed in the nucleus of each cell. But there's extra DNA not in the nucleus: mitochondrial DNA, used to generate energy, passed on only maternally, and originally passed to humans by bacteria. This DNA is often left off discussion of genomes.  In this case, I'd say they'd be including mitochondria for the sake of completeness.

Another small bone to pick. Microbiome is listed in Wikipedia as the sum total of microscopic organisms in a particular environment, and hologenome is used as an idea of co-evolution with microbes, roughly speaking. So the Scientific American article is pushing the envelope a bit.

So even within a scientific community the meaning of words can change over time until/unless locked down.

Further reading (both from Scientific American, as it happens):

• What happens when those useful bacteria disappear
• The appendix is useful - for the microbiome

Gravity and the narrow confines of life

Life on Earth has evolved within a very fine set of parameters.  We are going to find it a challenge to survive outside the sheltering cocoon of this planet, not the least because our atmosphere protects us from several types of radiation, not the least from our friendly sun.

Now there's another limitation.

Our body's physiological processes are to a great extent governed through the triggering of gene expression, which generates proteins that affect metabolic pathways of chemical reactions.  Translated, this means chemical signals trigger the unwrapping and copying of genes (sections of our DNA blueprint) that in turn generate proteins that... make our body work.

For that to happen, amongst other things we need... gravity.

On the one hand, one might intuit that gravity shouldn't be an essential part of our processes.  But we are generally pulled in a single direction: towards Earth, the largest mass at hand.  From an evolutionary perspective, that amount of gravity is an intrinsic part of the environment in which so many successive iterations (generations) successfully mutated and survived.  Our environment tempered the direction of successful mutation.

So it makes sense that our metabolic processes could be so finely tuned that significant change (ie, to zero gravity) could disrupt some of these processes.

And that's what's been found, as reported in New Scientist this week (4 February 2012).  Specifically: "weightless conditions... could disrupt the activity of 200 genes linked with immunity, metabolism and heat tolerance."

There is a slight caveat on that: the study used flies, and simulated weightlessness through magnetic fields.  Still, the researchers are confident of their results, it sounds plausible, and doubtless the result will be tested by others in other experimental contexts.

Still, just as science can bring the science fiction of space travel crashing to Earth, surely technological solutions will be developed.  After all, science fiction has already imagined simulated gravity.  It just hasn't filled in the details.

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.

The future of this blog [genetics 000]

It has come to my attention that...
I know I've been a bit slack lately...
There is so much richness in this world that there's never enough time to explore it all, let alone diarise it...

Ideally, I'd write a thought a day; heaven knows there is an abundance of fresh insights to be gleaned from the experiences of each and every day.  On the other hand, there's a putative obligation to pursue the insight to the full extent of its value, else why even start?

So, the world is still turning, new experiences are daily deposited in the bank of life's richness.  Where is the reward in not sharing it?

Time, that is the villain.  It seems to accelerate, leaving me guilty and struggling in its wake.

Not that I've been idle.  But as it stands, the less time I spend commuting, the less I have to devote to absorbing and recording.  (In any case, my commuting time had been taken up with podcasted lectures.)


To date, evolution constitutes the majority of my [tagged] posts.  Not surprising; it's been a fascinating journey - unexpected, and very rewarding.  But I've taken an equally fascinating, equally unexpected turn: to molecular biology and genetics.

Although the confluences could be mapped, this path certainly wasn't planned.  And I'm not a gadfly, turning to a new subject at whim.  In fact, before dipping into evolution, I'd not plunged so deeply into an area of study outside a formal university course.  And I had hitherto treated biology as the distant, neglected cousin of all the sciences, steeped as I had been in mathematics and physics.



A starting point could be: "what is a gene?"  Actually, I have attempted this in the past, with understandably mixed results.  So I felt I should not start the recording process until I'd got that under wraps.  Yet by the time I felt sufficiently confident, I'd come out the other end, and in fact discovered where within this wide area my true temperament and interest lies.

I will not start with the above question - the answer is not sufficiently straightforward.  I will start at the natural starting point: the basics of molecular biology.

It's not dry and uninteresting.  It's a fascinating universe writ small, and it touches on many of my core concerns, including information science, analysis, evolution, mathematics, and pure intrinsic beauty.


I will be trying to construct an engaging, coherent narrative.  Yet I will still take minor excursions into some of my traditional interests: music, film, current events, and science (first up will be a film called The Swimmer).

I even know exactly where this journey is taking me: genomics, wherein lies a universe of challenges - and which is one of the most current, most relevant worlds left to be explored.  For a hint of this, there's a truly inspiring lecture by Eric Lander of MIT, called Genomics (it's available for free on iTunes).  Although its clarity is worthy of the best of the visionary TED lectures, the full richness of its meaning will be far better appreciated with sufficient context.  That's what I'm aiming to provide.

More uses for "junk" DNA: developmental

Sex and junk. Two subjects of endless fascination for geneticists. Today: Junk.

Because there's been a new discovery that turns the notion of junk upside down.


Junk DNA seems to make up a high proportion of a typical genome: that is, we don't know what huge strings of coding information are for, but we don't think they do anything - simply because we haven't yet found functionality for them.

Wikipedia lists a few hypotheses for "junk DNA":
- a "reservoir of sequences" from which new functionality can emerge - in effect making it an important evolutionary nexus;
- useful space to more easily enable formation of necessary products such as enzymes (one of the least likely options, to my mind);
- undiscovered regulatory functions to control the expression of genes, particularly at developmental stages such as embryos;
- some junk may have regulatory layers for meaningful genetic programming (I'm not fully on top of this idea; I would have lumped it in with the one above);
- extrapolation from some genomes suggests eukaryotes (organisms with cellular nuclei) may "require a minimum of non-coding DNA" - but that minimum is said to be about 5%, whereas the human genome contains 95% junk.

Further possibilities include:
- evolutionary redundancy - for example, accidents in coding that are not deleterious and so remain within the DNA;
- viral insertions into germ-line cells, which are subsequently propagated into progeny.

That last is quite significant, as it has in recent times been demonstrated that a significant proportion of many genomes are viral in origin. This in itself is a significant vehicle for evolution, as viral DNA has often contributed useful functionality to the host.

But 95% junk DNA in the human genome? Intuition suggests much of that is of unknown functionality rather than junk per se.


Now Princeton University (datelined 20 May) reports an answer for at least some of the "junk". And it's close to the developmental concept above.


In Oxytricha, a single-celled pond-dwelling organism, what was considered junk has been found to trigger complex regroupings of DNA strands, during the development phase of the organism. Once the functionality has been completed, the gene's products are disposed of, and the genome trimmed down again.

It sounds like the process is so ephemeral that it is easily missed, especially since the evidence is subsequently destroyed. But the genes once labelled junk actually control the assemblage of other genes.

It sounds analogous to an assembly hierarchy: instructions beget miniature machines, which produce outputs and are then disassembled again.

To complicate matters, the researcher says "the instruction set comes in the form of RNA that is passed briefly from parent to offspring and these maternal RNAs provide templates for the rearrangement process". This might be analogous to a mother feeding an embryo necessary nutrients to enable growth, but this is a step beyond - it's at the DNA level.

One final thought. Much junk DNA consists of apparent stutters. That is, coding sequences that repeat ad nauseum, reverse, and otherwise follow semi-meaningless patterns. Some of that is viral in origin - which is not to say that it is or isn't currently useful. I expect that we will reclassify much junk as meaningful. As for the rest, will there be any DNA that is completely useless? On a macro level, unused functionality tends to atrophy and disappear over evolutionary time - unless it finds new functionality first, which happens surprisingly often. It's hard to say that the same principle of atrophy applies at a DNA level (the question is, how much cost there is to carrying an incremental amount of freeloading DNA) - but it certainly makes sense that mutation can result in new-found functionality at the DNA level. Mutations, after all, are akin to random scientific experiments: if something beneficial arises, it stands a reasonable chance of surviving.

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.

Evolution: Some further thoughts on radiation and mutation

Radiation is "in part responsible for the mutation that occurs in all organisms"*. In fact, I've heard little to suggest that there are any other significant [non-anthropogenic] causes of mutation (see previous post on mutation here).

Humans have happened upon this Earth about halfway through the planet's habitable lifespan. Putting aside terrestrial sources of radiation (both artificial and natural - they don't seem to figure significantly on the whole), it has been frequently noted that our atmosphere protects us from a large amount of cosmic radiation, solar and otherwise. The implication is that our atmospheric and solar characteristics dictate the "steady" rate of mutation experienced by life on this planet, which facilitates a stable - or life-fostering - evolutionary pace. It's interesting to speculate on the different radiation scenarios, and their possible outcomes. Too much cosmic radiation and mutation rates may go too high for good species cohesiveness; higher life forms may not develop. Too little radiation may mean insufficient adaptability to the planet's changing environment - Earth's environment for one has varied quite substantially in many directions over its history.

Given that we inhabit one of a very large number of solar systems in the outer reaches of our galaxy, it's plausible that other planetary systems may have developed along a similar path to ours. Speculation on how likely it is for there to be life anywhere near us would be a function of the density of our galactic neighbourhood, the likelihood of a similar solar system developing, and the range of tolerance of radiation for viable mutative life to evolve.

On an anecdotal basis (given the results of SETI to date), the suggestion is that there is nothing close by. But it would remain interesting to attempt the sums on the range of radiation that would foster an evolving biosystem.



*101 Key Ideas: Genetics, Jenkins, M (2000); Hodder & Stoughton, London.
This book has got some surprisingly sloppy writing and at least one incorrect diagram. But from time to time its descriptions give particularly useful insights.

Evolution: causes of mutation

Mutagens are those factors that cause mutation. Most sources list radiation and chemicals as the two types of mutagens. Some sources also add that there is a steady (background) amount of "natural" or "spontaneous" mutations. I haven't read enough about it to know whether this can be ascribed to a "natural" [terrestrial] amount of background radiation.

It is important to note that the implications of mutation - change in the original DNA base sequences of an organism - differ depending on whether the cell affected is a somatic or a germ cell. A mutation that occurs in a somatic, or body, cell will not affect heredity; the most notable outcome for a somatic mutation is cancer.

A mutation can be inherited if a) the DNA change has no significant impact on the viability of the cell, and the reproduction process, and b) it occurs in any of several types of germ cells - ie those cells that eventually give rise to the gamete egg or sperm.

Radiation in the ultraviolet wavelength can sometimes penetrate cells, and get absorbed by DNA, causing structural damage. Ionising radiation, which has a shorter wavelength than UV, is so called because it can knock electrons out of atoms, producing ions - which are more easily capable of taking part in chemical reactions. All organisms experience a small level of background radiation, which in origin can be either cosmic, solar or terrestrial (from either naturally occurring radioactive material or, more recently, human-originated).

At the DNA level, mutations can result in insertions of extra information (as base pairs), deletion of some pairs, or miscopying, such as transposition of sequences of base pairs.

Again, I wonder if "background" levels of ionising radiation are responsible for "background levels" of mutation. I would be interested to hear if any experiments have been done to establish causality: this could, for example, involve sufficiently shielding from background ratiation a sample of DNA-bearing organisms with a reasonably short generational span.

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".

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.

Science: New science snippets

New Scientist (right), the weekly British science news magazine, is often an embarassment of riches. When I had a weekly subscription, I ended up with rather a backlog of issues to consume my reading space.

The occasional issue is most welcome; this week's had a number of interesting items, some of which appear here today.


Creationism and science teachers
The US is the only western country for which creationism is a significant issue. Most of the rest of the world is accepting of scientific reason; or more correctly, most of the rest of the world doesn't have a powerful fundamentalist christian lobby voice.
A survey of science teachers (presumably secondary level) from Pennsylvania State University has found some interesting statistics - as well as a fair bit of the bleeding obvious. A quarter of the 900-odd respondents taught about creationism, and about half of those presented it as a valid scientific alternative to Darwinism.
Sixteen percent of these science teachers believe humans were created in the last 10,000 years.
So, half of those who raised the concept of creationism didn't teach that it was valid; and there was a number who thought it was valid, but didn't teach it.
Interestingly, it notes that the amount of class time given to evolution was higher, the more science education the science teachers themselves had. Making a rather good case for science teachers to be properly trained.
The study suggested that less-trained teachers felt less confidence engaging in the subject (ie responding to questions).
However, I strongly suspect that even where science is taught properly, a lot of those teachers would have a somewhat weak grasp of the two fundamental tenets of random mutation and natural selection, let alone the myriad implications that stem from them.

Inbreeding and genetic disorder
A review of studies from Murdoch University in Western Australia examined genetic disorders amongst the offspring of first cousins. This would be a rather surrogate measure, of course, of the effects of inbreeding. The study found a 1.2% higher rate of infant mortality of offspring of first cousins, compared to the overall population. Another such (review) study in 2002 found a similar order of magnitude: less than 3%.

Artificial legs as a boost for runners
Recently was shown a prosthetic foot design that enabled high performance sprinting, notably in double amputee Oscar Pistorius. Claims then made that this unfairly boosted performance - which have now been tested.
Again, a proxy measure was used to determine any advantage conferred: the amount of calories burnt per distance - ie whether it was cheaper to fuel the prostheses.
The answer given was no - it wasn't more efficient. So Pistorius is free to compete in the Olympics - unless some other hurdle appears.

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.

A chimeric cure: donor takeover

A unique medical case reported in the New England Journal of Medicine in January is seen as an example of chimerism: that is, one body with genetic components of two distinct entities.

Around 2002, a nine-year-old girl from south of Sydney "contracted a virus that destroyed her liver". With less than two days to live, she was given a replacement liver. Normally, it would be expected that she would need to take immunosuppresant drugs for the rest of her life - which would leave her susceptible to opportunistic illnesses.

Nine month later, when she fell ill, it was discovered that her blood type had changed from O negative to O positive - that of her donor.

Effectively, the blood stem cells of the donor's liver penetrated the bone marrow, performing a bone marrow transplant. As a result the new liver was no longer treated as foreign. The girl's immune system had been almost totally replaced.

The story from Westmead Hospital's haematology head (Julie Curtin) was that the patient's remaining white blood cells (responsible for immunity) started breaking down the new O positive red blood cells, a process called haemolysis. This resulted in the patient being very sick for a while. The medical staff, in trying to recover the situation, tried the risky step of stopping the course of immunosurpressant (anti-rejection) drugs. The situation stabilised, and the patient recovered. Blood tests also showed she no longer had immunity to measles or mump, despite immunisation as a baby.

There is no recorded precedent for this, and no easy explanation. Some factors mooted include that the donor was young (12 years old), the recipient having a low white blood cell count, the original type of liver failure - and the original virus, cytomegalovirus, which can suppress the immune system.

Four years down the track, the situation appears to be permanent and stable; anti-rejection drugs are not needed.

Interesting to note some irony between the mythic history of chimeras and this actual outcome: this is a complete reversal of the traditional, perjorative depiction of monsters.

Knowing the answers would be a giant boon to medical treatment. I note that there is some research into inducing chimerism to achieve just such an outcome. However, as it stands I suspect most doctors would be extremely reluctant to replicate some of the risky situations involved.

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.