Archive for the ‘DNA’ Category
Epigenetics 8: some terms
The gene is not more ‘basic’ than the organism, or closer to ‘the essence of life’, whatever that means. Organisms have DNA codes, and they maintain external forms and behaviours. Both are equal and fundamental components of being. DNA does not even build an organism directly, but must work through complex internal environments of embryological development, and external environments of surrounding conditions. We will not know the core and essence of humanity when we complete the human genome project.
Stephen Jay Gould, ‘Magnolias from Moscow’, in Dinosaur in a Haystack, 1996
I remember ages ago promising that I’d start every blog piece with a quote, then I more or less immediately forgot about it. Anyway the above quote kind of refers to epigenetics, and anticipates, in a way, the disappointment that many have felt about the human genome project and its not-quite-revelatory nature. As we learn more about the complexities of epigenetics, more about the relationships between genotype and phenotype will be revealed, but the process will surely be very gradual, though relentless. But I can’t talk, knowing so little. In this post, I’ll look at a very few key terms to help orient myself in this vast field. Not all will be specifically related to epigenetics, but to the whole field of DNA and genetics.
nucleosome: described as ‘the basic structural form of DNA packaging in eukaryotes’, it’s a segment of DNA wound round a histone ‘octamer’, a set of eight histones in a cubical structure. All of this is for fitting DNA into nuclei. Nucleosomes are believed to carry epigenetic info which modifies their core histones, and their positions in the genome are not random. Each nucleosome core particle consists of approximately 146 base pairs.
chromatin: a complex of DNA and protein, which packages DNA protectively, condensing the whole into a tight structure. Histones are essential components of chromatin. Chromatin structure is affected by methylation and acetylation of particular proteins, which in turn affects gene expression.
nucleotides: the basic building blocks of DNA and RNA, they consist of a nucleoside and a phosphate group. A nucleoside itself is a nitrogenous base (also known as a nucleobase) and a five-carbon sugar ribose (a ribose – these explanations always need more explaining – is a simple sugar, the natural form of which is D-ribose, and which comes in various structural forms). DNA and RNA are nucleic acid polymers made up of nucleotide monomers.
nucleobase: a nitrogenous base (e.g. adenine, cytosine, thymine, guanine, and uracil which replaces thymine in RNA), the fundamental units of our genetic code. Also simply known as a base.
base pairs: a base pair, in DNA, is one of the pairings adenine-thymine (A-T) or cytosine-guanine (C-G). They are pyrimidine-purine pairings. Adenine and guanine are purines, the other two pyrimidines. Due to their structure pyrimidines always pair with purines.
CpG islands: regions of DNA with a high frequency of CpG (C-G) sites, i.e. sites where a cytosine nucleotide is followed by a guanine nucleotide in linear sequence in a particular direction.
histones: highly alkaline proteins, the chief proteins of chromatin, and the means of ordering DNA into nucleosomes. There are four core histones, H2A, H2B, H3 and H4. These form an octamer structure, around which approximately 146 base pairs are wound.
Obviously, I’m very much a beginner at comprehending all this stuff, but I note that the number of videos on epigenetics seems to increase almost daily, which is raising my skepticism more than anything. I try to be selective in checking out these videos and other info on the topic, as there’s always this human tendency to claim super-solutions to our problems, as in super-foods and super-fitness regimes and the like. I’m more interested in the how of things, which is always a more complicated matter. Other information sources tend to assume knowledge or to skate over obvious complexities in a facile manner, and then of course there’s the ‘problem’ of being a dilettante, who wants to learn more about areas of scientific and historical knowledge often far removed from each other, and time’s running out, and we keep forgetting…
So anyway, I’ll keep plodding along, because it’s all quite interesting.
epigenetics and imprinting 7: more problems, and ICRs
the only image I can find that I really understand
In the previous post in this series I wrote about the connection between two serious disorders, Angelman syndrome and Prader-Willi syndrome, their connection to a missing small section of chromosome 15, and how they’re related to parental inheritance. These syndromes can sometimes also be traced back to uniparental disomy, in which the section of chromosome 15 is intact, but both copies are inherited from the mother (resulting in PWS) or the father (resulting in AS).
So the key here is that this small section of chromosome 15 needs to be inherited in the correct way because of the imprinting that comes with it. To take it to the genetic level, UBE3A is a gene which is only expressed from the maternal copy of chromosome 15. If that gene is missing in the maternal copy, or if, due to uniparental disomy, both copies of the chromosome are inherited from the father, UBE3A protein won’t be produced and symptoms of Angelman syndrome will appear. Similarly, PWS will develop if a certain imprinted gene or genes aren’t inherited from the father. Other imprinting disorders have been found, for example, one that leads to Beckwith-Wiedemann syndrome, though the mechanism of action is different, in that both copies of a gene on chromosome 11 are switched on when only the paternal copy should be expressed. This results in abnormal growth (too much growth) in the foetus. It too has an ‘opposite’ syndrome, Silver-Russell syndrome, in which the relevant protein expression is reduced, resulting in retarded growth and dwarfism.
But now to the question of exactly how genes are switched on and off, or expressed and repressed. DNA methylation, briefly explained in my first post on this topic, is essential to this. Methyl groups are carbon-hydrogen compounds which can be bound to a gene to switch it off, but here’s where I start to get confused. I’ll quote Carey and try to make sense of it:
… it may be surprising to learn that it is often not the gene body that is methylated. The part of the gene that codes for protein is epigenetically broadly the same when we compare the maternal and paternal copies of the chromosome. It’s the region of the chromosome that controls the expression of the gene that is differently methylated between the two genomes.
N Carey, The epigenetics revolution, 2011 p140
The idea, I now realise, is that there’s a section of the chromosome that controls the part of the gene that codes for the protein and it’s this region that’s differently methylated. Such regions are called imprinting control regions (ICRs). Sometimes this is straightforward, but it can get extremely complicated, with whole clusters of imprinted genes on a stretch of chromosome, being expressed from the maternally or paternally derived chromosomes, and not simply through methylation. An ICR may operate over a large region, creating ‘roadblocks’, keeping different sets of genes apart, and affecting thousands of base-pairs, not always in the same way. Repressed genes may come together in a ‘chromatin knot’, while other, activated genes from the same region form separate bundles.
Imprinting is a feature of brain cells – something which, as of the writing of Carey’s book (2011), is a bit of a mystery. Not so surprising is the number of expressed imprinted genes in the placenta, a place where competing paternal-maternal demands are played out. As to what is going on in the brain, Carey writes this:
Professor Gudrun Moore of University College London has made an intriguing suggestion. She has proposed that the high levels of imprinting in the brain represents a post-natal continuation of the war of the sexes. She has speculated that some brain imprints are an attempt by the paternal genome to promote behaviour in young offspring that will stimulate the mother to continue to drain her own resources, for example by prolonged breastfeeding.
N Carey, The epigenetics revolution, 2011. pp141-2
This sounds pretty amazing, but it’s a new epigenetic world we’re exploring. I’ll explore more of it next time.
References
The epigenetics revolution, by Nessa Carey, 2011
a DNA dialogue 4: purines, mostly
Canto: So what’s a pyrimidine, molecularly speaking, and why does it differ from a purine, and why does it matter?
Jacinta: They’re two different types of nitrogenous bases, dummy, which are a subset, maybe, of nucleotide bases. All of which is largely gobbledygook at present.
Canto: Ok, we know there are four different nitrogenous bases in DNA. Two of them, A & G, adenine and guanine, are purines, which structurally are two-carbon nitrogen ring bases. The other two, thymine and cytosine, T & C, are pyrimidines, which are one-carbon nitrogen ring bases. Uracil, in RNA, is also a pyrimidine. It replaces the thymine used in DNA.
Jacinta: That’s right, now we know that in DNA these nitrogenous bases are connected across the double helix, in pairs, in a particular way. A (a purine) always connects with T (a pyrimidine), and similarly C is always bonded to G. So why is this?
Canto: Why is it so? Well, put simply, the molecular structure of purines, which you’ll note have a two-carbon ring structure and so are larger than pyrimidines, doesn’t allow them to bond within the group, that’s to say with other purines, and the same goes with pyrimidines. It’s essentially due to the difference between hydrogen bond donors and acceptors for these groups.
Jacinta: So, looking at purines first, considering that they’re one of the building blocks of life, it’s not surprising that we find them in lots of the food we eat, especially in meat, mostly in organs like kidneys or liver. Structurally they’re heterocyclic aromatic organic compounds – as are pyrimidines. Heterocyclic simply means they have a ring structure composed of more than one element – in this case carbon and nitrogen. An aromatic compound isn’t quite what you think – structurally it means that it’s strong and stable, due to resonance bonds, which we won’t go into here. Below is a model of a purine molecule, which has the chemical formula C5H4N4 – the black globes are carbon atoms, the nitrogens are blue and the hydrogens white.
Purines and pyrimidines are both self-inhibiting and activating, so they actively bond with each other but inhibit self-bonding, so that they maintain a more or less equal amount as each other within the cell.
Canto: So that’s purines in general, but in DNA there are two purines, adenine and guanine, which must differ structurally – and are there any others?
Jacinta: Oh yes, caffeine is a purine, as well as uric acid…
Canto: Definitely aromatic.
Jacinta: And there are many others. Purines are very important molecules, used throughout the body for a variety of purposes, as components of ATP, cyclic AMP, NADH and coenzyme A, for example.
Canto: I’ve heard of some of those…
Jacinta: As to the difference between adenine and guanine, here’s how it’s described in this Research Gate article, which I’m sure is reliable:
The main difference between adenine and guanine is that adenine contains an amine group on C-6, and an additional double bond between N-1 and C-6 in its pyrimidine ring, whereas guanine contains an amine group on C-2 and a carbonyl group on C-6 in its pyrimidine ring
Canto: Shit, that explanation needs to be explained, please.
Jacinta: Haha well let’s look at more diagrammatic structures, but first – an amine group, also called an amino group, is a derivative of NH3 (ammonia), consisting of a nitrogen atom bonded to hydrogen atoms, at its simplest. This gives adenine the formula C5H5N5. Guanine has, in addition to the amine group, a carbonyl group, which is a carbon double bonded to an oxygen, C=O. This gives guanine the formula C5H5N5O. Anyway, it’ll all become clear over the next dozen or so years…
References
https://www.researchgate.net/publication/316984935_Difference_Between_Adenine_and_Guanine
https://en.wikipedia.org/wiki/Purine
https://en.wikipedia.org/wiki/Adenine
epigenetics and imprinting 6: when things go wrong
So imprinting involves parent-of-origin effects of which we find evidence in certain segments of certain chromosomes, in which genes are switched on or off, depending on inheritance. It often seems that these parent-of-origin effects counter-balance each other, as both parents have their own mutually exclusive way of trying to ensure the continuation of their genetic line.
It’ll be tough (for me) to take this down to a molecular level, but I’ll rely heavily on Nessa Carey’s book. It describes work on chromosome 7 in mice. I should first mention that there’s a convention in naming genes using italics, and the proteins they code for without italics. So there’s a gene in chromosome 7 called insulin-like growth factor 2 (Igf2) which promotes embryonic growth, and is usually expressed from the paternal copy. When researchers introduced a mutation which prevented the gene from effectively coding for the Igf2 protein, the offspring of this mutation were unaffected when the mutated gene was inherited from the mother, but the litter of offspring were much smaller when the gene was mutated in the father, showing that it was the paternal copy of the Igf2 gene that was required for foetal growth.
Fascinatingly for this ‘battle of the sexes’, there’s a gene in mouse chromosome 17 – Igf2r – which acts against the Igf2 protein, stopping it from promoting growth. This gene is also imprinted, from the maternal side. And so it goes.
According to Wikipedia, we now know of at least 80 imprinted genes in humans, mostly related to embryonic and placental growth and development. This is almost twice the amount Carey reported on less than a decade ago, so discoveries in this area are moving fast. As Carey writes, it’s uncertain whether there’s less imprinting in humans than in other mammals (we know of about 150 imprinted genes in mice) or whether they’re just harder to detect. Imprinting evolved about 150 million years ago (how do they know that? – as the much-treasured Bill Bryson would say), and is particularly prevalent amongst placental mammals.
This post was supposed to be about the mechanisms involved in imprinting, but my vast readership will have to wait awhile. I’m going to follow Carey, because I’m learning a lot from her, into the next area she writes about – ‘when imprinting goes bad’. She describes two very different conditions from birth, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). Researchers separately studying these conditions found that the parents of the sufferers were usually healthy, yet everything pointed to something genetic going on, presumably during the production of eggs or sperm.
The separate work on the origins of these two permanently debilitating but very different conditions eventually converged, when it was found that in both AS and PWS, the patients were missing a small, identical stretch of chromosome 15. What caused the two entirely different results of this defect was whether it was inherited from the mother (resulting in AS) or the father (resulting in PWS). So the disorder is epigenetically inherited, a further example of a parent-of-origin effect.
Yet some children inherit these disorders without any deletions to chromosome 15. They have two normal copies of chromosome 15 but not from each parent. Instead they have two copies from the mother and none from the father – called uniparental disomy. In another variation on the theme it was later discovered that AS was in some cases caused by the opposite form of uniparental disomy, in which two normal copies of the chromosome were inherited from the father. So, because the particular region of the chromosome is normally imprinted, it’s essential, for healthy offspring, that the region is inherited in the ‘correct’ way, from each parent.
I’ll be looking at more examples of problematic inheritance and imprinted genes next time.
References
https://en.wikipedia.org/wiki/Genomic_imprinting
Nessa Carey, The epigenetics revolution, 2011
a DNA dialogue 3: two anti-parallel strands
Jacinta: Ok so these two strands of DNA are described as anti-parallel. Is this just intended to confuse us?
Canto: Apparently not, in fact it’s quite essential. The useful q&a site Quora has good info on this, and understanding it in all its complexity should help us to understand DNA general – it’s one of a thousand useful entry points.
Jacinta: Yes, and I’ll try to explain. It became clear to us last time that the strands or ribbons twisted round in a double helix, called the backbone of the molecule, are made from phosphate and deoxyribose sugar, covalently bonded together. That means tightly bonded. Between the two strands, connecting them like ladder rungs, are nitrogenous bases (this is new to us). That’s adenine, thymine, guanine and cytosine, bonded together – A always to T, and C to G – with weak hydrogen bonds. We’ll have to look at why they must be paired in this way later.
Canto: It’s called Chargaff’s base pairing rule, which doesn’t tell us much.
Jacinta: And, according to a respondent from Quora, ‘the two strands of DNA are anti-parallel to each other. One of them is called leading strand, the other is lagging strand’. But I don’t quite get this. How are there two strands of DNA? I thought there was one strand with two sugar-phosphate backbones, and a rung made up of two – nitrogenous nucleobases? – weakly connected by hydrogen bonds.
Canto: I think the idea is there are two strands, with the attached bases, one next to another on the strand, and weakly attached to another base, or set of bases each attached to another phosphate-sugar backbone. As to why the whole thing twists, rather than just being a straight up-and-down ladder thing, I’ve no idea. Clearly we’re a couple of dopey beginners.
Jacinta: Well, many of the Quora respondents have been teaching molecular biology for years or are working in the field, and just skimming through, there’s a lot be learned. For now, being anti-parallel is essential for DNA replication – which makes it essential to DNA’s whole purpose if I can call it that. I’ll also just say that the sugars in the backbone have directionality, so that the way everything is structured, one strand has to go in the opposite direction for the replication to work. If for example the strands were facing in the same direction, then the base on one side would connect to a hydrophobic sugar (a good thing) but the base on the other side would be facing a hydrophilic phosphate (a bad thing). Each base needs to bond with a sugar – that’s to say a carbon atom, sugar being carbon-based – so one strand needs to be an inversion of the other. That’s part of the explanation.
Canto: Yes, I find many of the explanations are more like descriptions – they assume a lot of knowledge. For example one respondent says that the base pairs follow Chargaff’s rule and that means purines always pair up with pyrmidines. Not very helpful, unless maybe you’re rote-learning for a test. It certainly doesn’t explain anti-parallelism.
Jacinta: Well, although we don’t fully understand it yet, it’s a bit clearer. Anti-parallelism is an awkward term because it might imply, to the unwary, something very different from being parallel. The strands are actually parallel but facing in the opposite direction, and when you think about the structure, the reason for that becomes clearer. And imagining those backbone strands facing in the same direction immediately shows you the problem, I think.
Canto: Yes and for more insight into all that, we’ll need to look more closely at pyrmidines and purines and the molecular structure of the backbone, and those bases, and maybe this fellow Chargaff.
References
A DNA dialogue 2: the double helix
Canto: Ok we talked about base pairs at the end of dialogue 1. A (nucleo)base pair is, duh, a pairing of nucleobases. There are four types of base in DNA – adenine and thymine, which always pair together, and the other pairing, cytosine and guanine.
Jacinta: Please explain – what’s a nucleobase, what do they do, and why do they come in pairs?
Canto: Well, let’s see, how do we begin… DNA stands for deoxyribonucleic acid…
Jacinta: So it’s an acid. But bases are like the opposite of acids aren’t they? So how can an acid be constructed of its opposite?
Canto: Look, I can’t answer that right now – I haven’t a clue – but let’s keep investigating the structure and function, and the answers might come. So, you’ll know that there was a battle in the 1950s to elucidate the structure of DNA, and it was found to form a double helix two strands of – I don’t know what – connected to each other in a twisted sort of way by, I think, those base pairs connected by hydrogen bonds. Anyway, here’s a fairly typical explanation, from Nature Education, which we’ll try to make sense of:
The double helix describes the appearance of double-stranded DNA, which is composed of two linear strands that run opposite to each other, or anti-parallel, and twist together. Each DNA strand within the double helix is a long, linear molecule made of smaller units called nucleotides that form a chain. The chemical backbones of the double helix are made up of sugar and phosphate molecules that are connected by chemical bonds, known as sugar-phosphate backbones. The two helical strands are connected through interactions between pairs of nucleotides, also called base pairs. Two types of base pairing occur: nucleotide A pairs with T, and nucleotide C pairs with G.
Jacinta: So I think I have a problem with this description. I think I need a picture, fully labelled. So the two strands themselves are made up of nucleotides, and the connections between them are made up of bonded sugar and phosphate molecules? But the strands are connected, via sugar and phosphate, in particular ways – ‘through interactions’ – which only allow A to pair with T, and C to pair with G?.
Canto: I think that’s right. Maybe we can find a picture.
Jacinta: Ok, so we got it completely wrong. The backbone, of sugar-phosphate, is the outer, twisted strand, or two of them, like the vertical bars of a twisted ladder, or the toprails of a spiral staircase, and the base pairs are like the stairs themselves, made of two separate parts, the bases, bonded together by hydrogen…
Canto: Forget the description, the picture above is worth all our words. It also tells us that the DNA molecule is around 2 nanometres wide. That’s two billionths of a metre. And 3.4 nanometres long for a full twist of the double helix, I think.
Jacinta: Whateva. There’s also this claim that the two strands are ‘anti-parallel’. It looks to me as if they’re simply parallel, but twisted. What does this mean? Is it significant?
Canto: I don’t know – maybe we’ll find out next time. I’m already exhausted.
Jacinta: …….
A DNA dialogue 1: the human genome
Canto: I’m often confused when I try to get my head around all the stuff about genes and DNA, and genomes and alleles and chromosomes, and XX and XY, and mitosis and meiosis, and dominant and recessive and so on. I’d like to get clear, if only I could.
Jacinta: That’s a big ask, and of course we’re both in the same boat. So let’s use the magical powers of the internet to find answers. For example, here’s something that confuses me. The Human Genome project, which ended around the year 2000, involved a mapping of the whole human genome, and that includes coding and non-coding genes, and I think it was found to contain 26,000 or so – what? Letters? Genes? Coding genes? Anyway there’s a number of questions there, but they’re not the questions that confuse me. I don’t get that we now, apparently, have worked out the genetic code for all humans, but each of us has different DNA. How, exactly, does our own individual DNA relate to the genome that determines the whole species? Presumably it’s some kind of subset?
Canto: Hmmm. This article from the Smithsonian tells us that the genetic difference between human individuals is very tiny, at around 0.1%. We humans differ from bonobos and chimps, two lineages of apes that separated much more recently, by about 1.2%….
Jacinta: Yes, yes, but how, with this tiny difference between us, are we able to use DNA forensically to identify individuals from a DNA sample?
Canto: Well, perhaps this Smithsonian article provides a clue. It says that the 1.2% difference between us and chimps reflects a particular way of counting. I won’t go into the details here but apparently another way of counting shows a 4-5% difference.
Jacinta: We probably do need to go into the details in the end, but clearly this tiny .1% difference between humans is enough for us to determine the DNA as coming from one individual rather than 7 to 8 billion others. Strangely enough, I can well believe that, given that we can detect gravitational waves and such – obviously using very different technology.
Canto: Yeah the magic of science. So the Human Genome Project was officially completed in April 2003. And here’s an interesting quote from Wikipedia:
The “genome” of any given individual is unique; mapping the “human genome” involved sequencing a small number of individuals and then assembling these together to get a complete sequence for each chromosome. Therefore, the finished human genome is a mosaic, not representing any one individual.
Of course it would have to be a mosaic, but how can it represent the whole human genome when it’s only drawn from a small number? And who were these individuals, how many, and where from?
Jacinta: The Wikipedia article does give more info on this. It tells us that the project isn’t really finished, as we’ve developed techniques and processes for faster and deeper analyses. As to your questions, when the ‘finished’ sequencing was announced, the mosaic was drawn from a small number of anonymous donors, all of European origin.
Canto: But we all originated from Africa anyway, so…
Jacinta: So maybe recent ‘origin’ isn’t so important. Anyway, that first sequencing is now known as the ‘reference genome’, but after that they did sequence the genomes of ‘multiple distinct ethnic groups’, so they’ve been busy. But here are some key findings, to finish off this first post. They found some 22,300 protein-coding genes, as well as a lot of what they used to call junk DNA – now known as non-coding DNA. That number is within the mammalian range for DNA, which no doubt surprised many. Another blow for human specialness? And they also found that there were many more segmental duplications than expected. That’s to say, sections of DNA that are almost identically repeated.We’ll have to explore the significance of this as we go along.
Canto: Yes, that’s enough for starters. Apparently our genome has over 3 billion nucleobase pairs, about which more later no doubt.
References
epigenetics and imprinting 4: the male-female thing
Gametes are gametes because of epigenetic modifications in their pro-nuclei, but they have to lose these modifications, or transform them, when they come together to form zygotes. The male pro-nucleus DNA methylation is stripped away immediately after sperm penetrates egg. The egg pronucleus undergoes the same process, but more gradually. It’s like a wiping away of epigenetic memory, creating totipotency, which becomes a more limited pluripotency as the blastocyst, with its inner cell mass (ICM), forms.
The ICM cells begin differentiating through the regulation of some key genes. For example, a gene codes for a protein that switches on a set of genes, which code for proteins in a cascading effect. But it’s not quite a matter of switching genes on or off, it’s rather more complex. The process is called gene reprogramming, and it’s of course done effortlessly during every reproductive cycle. Artificial reprogramming of the kind carried out by Yamanaka and others, an essential part of cloning, hasn’t come close to this natural process that goes on in mammals and other species every day.
Clearly, though the epigenetic reprogramming for the female pronucleus is different from that carried out more swiftly in the male. As Carey puts it, ‘the pattern of epigenetic modifications in sperm is one that allows the male pronucleus to be reprogrammed relatively easily.’ Human researchers haven’t been particularly successful in reprogramming an adult nucleus by various methods, such as transferring it to a fertilised egg or treating it with the four genes isolated by Yamanaka. The natural process of gene reprogramming eliminates most of the epigenetic effects accumulated in the parent genes, but as the reprogramming is a different process in the male and female pro-nucleus, this shows that they aren’t functionally equivalent. There is a ‘parent-of-origin effect’. Experiments done on mice to explore this effect found that DNA methylation, an important form of chromatin modification (and the first one discovered), was passed on to offspring by the female parent. That’s to say, DNA from the female was more heavily methylated than that from the male. Carey describes the DNA as ‘bar-coded’ as coming from the male or the female. The common term for this is imprinting, and it’s entirely epigenetic.
Imprinting has been cast by Carey, and no doubt others, as an aspect of the ‘battle of the sexes’. This battle may well be imprinted in the pronuclei of the fertilised egg. Here’s how Carey puts the two opposing positions:
Male: This pregnant female is carrying my genes in the form of this foetus. I may never mate with her again. I want my foetus to get as big as possible so that it has the greatest chance of passing on my genes.
Female: I want this foetus to pass on my genes. But I don’t want it to be at the cost of draining me so much that I never reproduce again. I want more than this one chance to pass on my genes.
So there’s a kind of balance that has developed in we eutherian mammals, in a battle to ensure that neither sex gains the upper hand. Further experiments on mice in recent times have explored how this battle is played out epigenetically. I’ll look at them in the next post in this series.
Reference
The Epigenetics Revolution, by Nessa Carey, 2011
clever Charlie Darwin
A photo taken by me! King Charles seated in state in the Musuem of Natural History, London. It was a thrill to be granted an audience
I recently decided to reread Darwin’s Origin of Species, which was really reading it for the first time as my first reading was pretty cursory, and I could barely follow the wealth of particular knowledge he used for cumulative effect to adduce his theory. This time I’ve been doing a closer reading, and becoming increasingly impressed, and I’ve only read the first chapter, ‘Variation under Domestication’.
Darwin’s argument here of course is that domesticated horses, dogs, birds and plants have been artificially selected over long periods of time, and often unconsciously, to suit human needs and tastes. This might seem screamingly obvious today, and to a degree it was recognised in Darwin’s time, but because of an inability to take the long view, and also because of the then-prevalent paradigm of the fixity of species, breeders and nurserymen tended to under-estimate their own cumulative powers, and to claim, for example, that dogs and pigeons had always come in many varieties. Even Darwin was uncertain, and was willing to concede – writing of course before the advent of Mendelian genetics, never mind the revolution wrought by the identification and analysis of DNA as the molecule of inheritance – that in some cases the breeders might be right:
In the case of most of our anciently domesticated animals and plants, I do not think it is possible to come to any definite conclusion, whether they have descended from one or several species.
He was even prepared to concede that it was ‘highly probable that our domestic dogs have descended from several wild species’, while at the same time arguing that the breeding of dogs, in Egypt, other parts of Africa and Australia (where, in his Beagle travels, he observed dingoes, which he may have seen as semi-domesticated by the Aborigines) extended back far further in time than most people suspected. We now know that Darwin’s concession here was ‘premature’. The latest research strongly suggests that our domesticated dogs trace their ancestry to a group of European wolves dating from 19,000 to 32,000 years ago, and probably now extinct. That’s a time-frame Darwin would’ve baulked at, and it’s both funny and kind of tragic that this is something I’ve ‘discovered’ after 30 seconds of selective internet searching. There’s no doubt, though that Darwin’s bold but always informed speculations were heading in the right direction.
Particularly informed – and bold – were his speculations about pigeons. This is hardly surprising as he spent several years studying and breeding them himself. Interestingly, he started doing so because he’d become convinced that all the fancy pigeons then on show were most likely derived from one common species, the rock pigeon or rock dove (Columba livia), a view already held by some naturalists but few breeders. He devotes several pages in Chapter 1 to arguing his case, for example pointing out that the ‘several distinct species’ argued for by breeders can be crossed with complete success, that’s to say with no signs of sterility or more than usually defective offspring.
So, as with dogs, I decided to look up what the latest research was on the ancestry of English carriers, short-faced tumblers, runts, fantails, common tumblers, barbs, pouters, trumpeters and laughers, to name some of the pigeons Darwin mentions in the chapter, and was excited to find that a piece of research published as recently as 2013 has confirmed Darwin’s hypothesis. Cheaper and faster genome sequencing technologies have enabled researchers to sequence the genomes of many wild and domesticated birds, and they’ve found that all of the latter are clearly closer to C livia than to any other wild species. It only took just over 150 years for Darwin to be proven correct.
Close reading like this really does reap some fun rewards, and I’ll finish with two more examples. Darwin wrote of how in the world of breeding, quite a drastic change can be brought about in one breeding step, as in the case of the fuller’s teasel with its hooks. He goes on:
So it has probably been with the turnspit dog; and this is known to have been the case with the ancon sheep.
Not knowing wtf he was talking about, I irritatedly decided to look up these unknown creatures. The turnspit dog is a now-extinct breed, bred specifically from around the 16th century to provide the dogpower to turn meat on a spit, the only conceivable way of cooking large joints of meat in your average fancy household for a couple of centuries. The dog, or dogs, because the system worked better if you had two of them engaged in shift work, turned a wheel by running inside it, rat-like, until the meat was cooked. They were known to be long-bodied and short-legged, but details of how they were bred aren’t known, as they were apparently beneath scholarly consideration. They certainly weren’t seen as cuddly pets – if you treat creatures as slaves it heightens your contempt for then (cf Aristotle) – and they were even taken to church as foot-warmers. They’d disappeared entirely by the end of the 19th century.
It’s a dog’s life?
The ancon sheep was a short-legged type, apparently bred from a single individual in the USA in the late nineteenth century, its short legs having the singular advantage, to some, of curtailing its hopes of freedom by jumping the fence. The term ‘ancon’ has since been used by breeding researchers to describe strains of creatures arising from an individual with the same phenotype.
Einstein, science and the natural world: a rabid discourse
Einstein around 1915
Canto: Well, we’re celebrating this month what is surely the greatest achievement by a single person in the history of science, the general theory of relativity. I thought it might be a good time to reflect on that achievement, on science generally, and on the impetus that drives us to explore and understand as fully as possible the world around us.
Jacinta: The world that made us.
Canto: Précisément.
Jacinta: Well, first can I speak of Einstein as a political animal, because that has influenced me, or rather, his political views seem to chime with mine. He’s been described as a supra-nationalist, which to me is a kind of political humanism. We’re moving very gradually towards this supra-nationalism, with the European Union, the African Union, and various intergovernmental and international organisations whose goals are largely political. Einstein also saw the intellectual venture that is science as an international community venture, science as an international language, and an international community undertaking. And with the development of nuclear weapons, which clearly troubled him very deeply, he recognised more forcefully than ever the need for us to take international responsibility for our rapidly developing and potentially world-threatening technology. In his day it was nuclear weapons. Today, they’re still a threat – you’ll never get that genie back in the bottle – but there are so many other threats posed by a whole range of technologies, and we need to recognise them, inform ourselves about them, and co-operate to reduce the harm, and where possible find less destructive but still effective alternatives.
Canto: A great little speech Jas, suitable for the UN general assembly…
Jacinta: That great sinkhole of fine and fruitless speeches. So let’s get back to general relativity, what marks it off from special relativity?
Canto: Well I’m not a physicist, and I’m certainly no mathematician, but broadly speaking, general relativity is a theory of gravity. Basically, after developing special relativity, which dealt with the concepts of space and time, in 1905, he felt that he needed a more comprehensive relativistic theory incorporating gravity.
Jacinta: But hang on, was there really anything wrong with space and time before he got his hands on them? Why couldn’t he leave them alone?
Canto: OMG, you’re taking me right back to basics, aren’t you? If I had world enough, and time…
Jacinta: Actually the special theory was essentially an attempt – monumentally successful – to square Maxwell’s electromagnetism equations with the laws of Newton, a squaring up which involved enormous consequences for our understanding of space and time, which have ever since been connected in the concept – well, more than a concept, since it has been verified to the utmost – of the fourth, spacetime, dimension.
Canto: Well done, and there were other vital implications too, as expressed in E = mc², equivalating mass and energy.
Jacinta: Is that a word?
Canto: It is now.
Jacinta: So when can we stop pretending that we understand any of this shite?
Canto: Not for a while yet. The relevance of relativity goes back to Galileo and Newton. It all has to do with frames of reference. At the turn of the century, when Einstein was starting to really focus on this stuff, there was a lot of controversy about whether ‘ether’ existed – a postulated quasi-magical invisible medium through which electromagnetic and light waves propagated. This ether was supposed to provide an absolute frame of reference, but it had some contradictory properties, and seemed designed to explain away some intractable problems of physics. In any case, some important experimental work effectively quashed the ether hypothesis, and Einstein sought to reconcile the problems by deriving special relativity from two essential postulates, constant light speed and a ‘principle of relativity’, under which physical laws are the same regardless of the inertial frame of reference.
the general theory – get it?
Jacinta: What do you mean, ‘the initial frame of reference’?
Canto: No, I said ‘the inertial frame of reference’. That’s one that describes all parameters homogenously, in such a way that any such frame is in a constant motion with respect to other such frames. But I won’t go into the mathematics of it all here.
Jacinta: As if you could.
Canto: Okay. Okay. I won’t go any further in trying to elucidate Einstein’s work, to myself, you or anyone else. At the end of it all I wanted to celebrate the heart of Einstein’s genius, which I think represents the best and most exciting element in our civilisation.
Jacinta: Drumroll. Now, expose this heart to us.
Canto: Well we’ve barely touched on the general theory, but what Einstein’s work on gravity teaches us is that by not leaving things well alone, as you put it, we can make enormous strides. Of course it took insight, hard work, and a full and deep understanding of the issues at stake, and of the work that had already been done to resolve those issues. And I don’t think Einstein was intending to be a revolutionary. He was simply exercised by the problems posed in trying to understand, dare I say, the very nature of reality. And he rose to that challenge and transformed our understanding of reality more than any other person in human history. It’s unlikely that anything so transformative will ever come again – from the mind of a single human being.
Jacinta: Yes it’s an interesting point, and it takes a particular development of culture to allow that kind of transformative thinking. It took Europe centuries to emerge from a sort of hegemony of dogmatism and orthodoxy. During the so-called dark ages, when warfare was an everyday phenomenon, and later too, right through to the Thirty Years War and beyond, one thing that could never be disputed amongst all that disputation was that the Bible was the word of God. Nowadays, few people believe that, and that’s a positive development in the evolution of culture. It frees us to look at morality from a broader, richer, extra-Biblical perspective..
Canto: Yes we no longer have to even pretend that our morality comes from such sources.
Jacinta: Yes and I’m thinking of other parts of the world that are locked in to this submissive way of thinking. A teaching colleague, an otherwise very liberal Moslem, told me the other day that he didn’t believe in gay marriage, because the Qu-ran laid down the law on homosexuals, and the Qu-ran, because written by God, is perfect. Of course I had to call BS on that, which made me quite sad, because I get on very well with him, on a professional and personal basis. It just highlights to me the crushing nature of culture, how it blinds even the best people to the nature of reality.
Canto: Not being capable of questioning, not even being aware of that incapability, that seems to me the most horrible blight, and yet as you say, it wasn’t so long ago that our forebears weren’t capable of questioning the legitimacy of Christianity’s ‘sacred texts’, in spite of interpreting those remarkably fluid texts in myriad ways.
Jacinta: And yet out of that bound-in world, modern science had its birth. Some modern atheists might claim the likes of Galileo and Francis Bacon as one of their own, but none of our scientific pioneers were atheists in the modern sense. Yet the principles they laid down led inevitably to the questioning of sacred texts and the gods described in them.
Canto: Of course, and the phenomenal success of the tightened epistemology that has produced the scientific and technological revolution we’re enjoying now, with exoplanets abounding, and the revelations of Homo floresiensis, Homo naledi and the Denisovan hominin, and our unique microbiome, and recent work on the interoreceptive tract leading to to the anterior insular cortex, and so on and on and on, and the constant shaking up of old certainties and opening up of new pathways, all happening at a giddying accelerating rate, all of this leaves the ‘certainty of faith’ looking embarrassingly silly and feeble.
Jacinta: And you know why ‘I fucking love science’, to steal someone else’s great line? It’s not because of science itself, that’s only a means. It’s what it reveals about our world that’s amazing. It’s the world of stuff – animate and inanimate – that’s amazing. The fact that this solid table we’re sitting at is made of mostly empty space – a solidity consisting entirely of electrochemical bonds, if that’s the right term, between particles we can’t see but whose existence has been proven a zillion times over, and the fact that as we sit here on a still, springtime day, with a slight breeze tickling our faces, we’re completely oblivious of the fact that we hurtling around on the surface of this earth, making a full circle every 24 hours, at a speed of nearly 1700 kms per hour. And at the same time we’re revolving around the sun at a far greater speed, 100,000 kms per hour. And not only that, we’re in a solar system that’s spinning around in the outer regions of our galaxy at around 800,000 kilometres an hour. And not only that… well, we don’t feel an effing thing. It’s the counter-intuitive facts about the natural world that our current methods of investigation reveal – these are just mind-blowing. And if your mind doesn’t get blown by it, then you haven’t a mind worth blowing.
Canto: And we have two metres of DNA packed into each nucleus of the trillions of cells in our body. Who’d’ve thunkit?
whatever