Archive for the ‘epigenetics’ Category
reading matters 7
She has her mother’s laugh, by Carl Zimmer , science author and journalist, blogger, New York Times columnist, etc etc
content hints – inheritance and heredity, genetics and epigenetics, Darwin and Galton, the Hapsburg jaw, eugenics, Hugo de Vries, Theodor Boveri, Luther Burbank, Pearl and Carol Buck, Henry Goddard, The Kallikak Family, Hitler’s racial hygiene laws, morons, the five races etc, Frederick Douglass, Thomas Hunt Morgan, Emma Wolverton, PKU, chromosomal shuffling, meiosis, cultural inheritance, mitochondrial DNA, Mendel’s Law, August Weismann, germ and soma, twin studies, genetic predispositions, mongrels, Neanderthals, chimeras, exosomes, the Yandruwandha people, IVF, genomic engineering, Jennifer Doudna, CRISPR, ooplasm transfers, rogue experiments, gene drives, pluripotency, ethical battlegrounds.
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
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
epigenetics and imprinting 5: mouse experiments and chromosome 11
So we were looking at how we – mammals amongst others – are engaged in a kind of battle for the best way to ensure our genetic survival into the future, beyond our insignificant little selves. This battle begins in the very early phase of life, as zygotes multiply to form a blastocyst.
Remember from my last post on this topic, the male mammal is interested in the offspring above all else. He’s even happy to sacrifice the mother for the sake of the child – after all there’s plenty more fish in the sea (or mammals in the – you know what I mean). The female, on the other hand, is more interested in self-preservation than in this pregnancy. She wants more than one chance to pass on her genes.
So, by the blastocyst stage, cells have differentiated into those that will form the placenta and those that will form the embryo itself. Experiments on mice have helped to elucidate this male-female genetic struggle. Mouse zygotes were created which contained only paternal DNA and only maternal DNA. These different zygotes were implanted into the uterus of mice. As expected, the zygotes didn’t develop into living mice – it takes DNA from both sexes for that. The zygotes did develop though, but with serious abnormalities, which differed depending on whether they were ‘male’ or ‘female’. In those in which the chromosomes came from the mother, the placental tissues were particularly underdeveloped. For those with the male chromosomes, the embryo was in a bad way, but the placental tissues not so much.
In short, these and other experiments suggested that the male chromosomes favoured placental development while the female chromosomes favoured the embryo. Thus, the male chromosomes are ‘aiming’ to build up the placenta to drain as many nutrients as possible from the mother and feed them into the foetus. The female chromosomes have the opposite aim, resulting in a ‘fine balance’ in the best scenarios.
Further work in this area has identified particular chromosomes responsible for these developments, and some of the epigenetic factors involved. For example, mouse chromosome 11 is important for offspring development. When the offspring inherits a copy of chromosome 11 from each parent, the offspring will be of normal size. If both copies come from the mother it will abnormally small, while if both come from the father it will be abnormally large. These experiments were carried out on inbred mice with identical DNA. Nessa Carey summarises:
If you sequenced both copies of chromosome 11 in any of the three types of offspring, they would be exactly the same. They would contain the same millions of A, C, G and T base-pairs, in the same order. But the two copies of chromosome 11 do clearly behave differently at a functional level, as shown by the different sizes of the different types of mice. Therefore there must be epigenetic differences between the maternal and paternal copies of chromosome 11.
So this means that chromosome 11 is an imprinted chromosome – or at least certain sections of it. This is the same for other chromosomes, some of which aren’t imprinted at all. But how is it done? That’s the complex biochemical stuff, which I’ll try to elucidate in the next post on this topic.
Footnote: the photo above shows a bi-maternal mouse with healthy offspring, and further work in deleting imprinted genetic regions has allowed researchers to create healthy bi-paternal mice too. There’s a fascinating account of it here.
References:
Nessa Carey, The epigenetics revolution, 2011
https://www.the-scientist.com/news-opinion/first-mouse-embryos-made-from-two-fathers-64921
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
epigenetics and imprinting 3: at the beginning
A zygote is the union of two gametes (haploid cells), the sperm and the egg. It’s the first diploid cell, from which all the other diploid cells – scores of trillions of them – are formed via mitosis.
What’s interesting about this from an epigenetic perspective is that gametes are specialised cells, but zygotes are essentially totipotent – the least specialised cells imaginable – and all this has to do with epigenetics.
I’m not entirely clear about what happens to turn specialist gametes into totipotent zygotes, and that’s what I’m trying to find out. I’m not sure yet whether zygotes immediately start differentiating as they divide and multiply or whether the first divisions – in what is called the zygote phase, which eventually forms the blastocyst – form an identical set of zygotes.
The two-week period of these first divisions is called the germinal phase. During this phase zygotes divide mitotically while at the same time moving, I’m not sure how, from the fallopian tube to the uterus. Apparently, after the first few divisions, differentiation starts to occur. The cells also divide into two layers, the inner embryo and the outer placenta. The growing group of cells is called a blastocyst. The outer layer burrows into the lining of the uterus and continues to create a web of membranes and blood vessels, a fully developed placenta.
But, as Nessa Carey would say, this is a description not an explanation. How does this initial cell differentiation – into the outer layer (trophectoderm), which becomes the placenta and other extra-embryonic tissues, and the inner cell mass (ICM) – come about? Understanding these mechanisms, and the difference between totipotent cells (zygotes) and pluripotent cells (embryonic stem cells) is clearly essential for comprehending, and so creating, particular forms of life. This PMC article, which examines how the trophectoderm is formed in mice, demonstrates the complexity of all this, and raises questions about when the ‘information’ that gives rise to differentiation becomes established in these initial cells. Note for example this passage from the article, which dates to 2003:
It is now generally accepted that trophectoderm is formed from the outer cell layer of the morula, while the inner cells give rise to the ICM, which subsequently forms the epiblast and primitive endoderm lineages. What remains controversial, however, is whether there is pre-existing information accounting for these cell fate decisions earlier than the 8-cell stage of development, perhaps even as early as the oocyte itself.
The morula is the early-stage embryo, consisting of 16 totipotent cells. The epiblast is a slightly later differentiation within the ICM. An oocyte is a cytoplasm-rich, immature egg cell.
Molecular biologists have been trying to understand cell differentiation by working backwards, trying to turn specialised cells into pluripotent stem cells, mostly through manipulating their nuclei. You can imagine the benefits, considering the furore created a while back about the use of embryonic stem (ES) cells in medical treatments. To be able to somehow transform a liver or skin cell into this pluripotential multi-dimensional tool would surely be a tremendous breakthrough. Most in the field, however, considered such a transformation to be little more than a pipe-dream.
Carey describes how this breakthrough occurred. Based on previous research, Shinya Yamanaka and his junior associate Kazutoshi Takahashi started with a list of 24 genes already found to be ‘pluripotency genes’, essential to ES cells. If these genes are switched off experimentally, ES cells begin to differentiate. The 24 genes were tested in mouse embryonic fibroblasts, and, to massively over-simplify, they eventually found that only 4 genes, acting together, could transform the fibroblasts into ES-type cells. Further research confirmed this finding, and the method was later found to work with non-embryonic cells. The new cells thus created were given the name ‘induced pluripotent stem cells’, or iPS cells, and the breakthrough has inspired a lot of research since then.
So what exactly does this have to do with epigenetics? The story continues.
epigenetics and imprinting 2: identical genes and non-identical phenotypes
I’ve now listened to a talk given by Nessa Carey (author of The epigenetic revolution) at the Royal Institution, but I don’t think she even mentioned imprinting, so I may not mention it again in this post, but I’ll get back to it.
The talk was of course easier to follow than the book, and it didn’t really teach me anything new, but it did hammer home some points that I should’ve mentioned at the outset, and that is that it’s obvious that genetics isn’t the whole story of our inheritance and development because it doesn’t begin to explain how, from one fertilised egg – the union of, or pairing of, two sets of chromosomes – we get, via divisions upon divisions upon divisions, a complex being with brain cells, blood cells, skin cells, liver cells and so forth, all with identical DNA. It also doesn’t explain how a maggot becomes a fly with the same set of genes (or a caterpillar becomes a butterfly, to be a little more uplifting). These transformations, which maintain genetic inheritance while involving massive change, must be instigated and shaped by something over and above genetics but intimately related to it – hence epigenetics. Other examples include whether a crocodile hatchling will turn out male or female – determined epigenetically via the temperature during development, rather than genetically via the Y chromosome in mammals.
So, to add to the description I gave last time, the histone proteins that the DNA wraps itself round come in batches or clusters of eight. The DNA wraps around one cluster, then another, and so on with millions of these histone clusters (which have much-studied ‘tails’ sticking out of them). And I should also remind myself that our DNA comes in a four-letter code strung together, out of which is constructed 3 billion or so letters.
The detailed description here is important (I hope). One gene will be wrapped around multiple histone clusters. Carey, in her talk, gave the example of a gene that breaks down alcohol faster in response to consumption over time. As Carey says, ‘[the body] has switched on higher expression of the gene that breaks down alcohol’. The response to this higher alcohol consumption is that signals are generated in the liver which induce modifications in the histone tails, which drive up gene expression. If you then reduce your alcohol consumption over time, further modifications will inhibit gene expression. And it won’t necessarily be a matter of off or on, but more like less or more, and the modifications may relate to perhaps an endless variety of other stimuli, so that it can get very complicated. We’re talking about modifications to proteins but there can also be modifications to DNA itself. These modifications are more permanent, generally. This is what creates specialised cells – it’s what prevents brain cells from creating haemoglobin, etc. Those genes are ‘tightened up’ or compacted in neurons by the modifying agents, so that, for example, they’re permanently unable to express the haemoglobin-creating function.
All of this is extremely fascinating and complex, of course, but the most fascinating – the most controversial and headline-creating stuff – has to do with carrying epigenetic changes to the next generation. The inheritance of acquired characteristics, no less. Next time.
References
What is epigenetics? with Nessa Carey – The Royal Institution (video)
The Epigenetics Revolution, by Nessa Carey, 2011
epigenetics and imprinting 1 – it’s complex
The last book I read was The Epigenetics Revolution by Nessa Carey, though I’m not sure if I’ve really read it. So much of it was about persisting with the next sentence though I hadn’t fully understood the previous one. Biochemistry does that to me – too many proteins, versions of RNA, transposons, transferases, suppressors, catalysers, adjuvants and acronyms. And in the end I’m not at all sure how much progress we’re making in this apparently tantalising field.
So I’m going to pick out imprinting for starters, as a way of familiarising myself a little more with the epigenetic process of leaving tabs or marks on specific genes.
I know nothing about imprinting. Isn’t it what female birds do with their offspring, even when they’re still in the shell? Here’s how Wikipedia introduces it :
Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. As of 2014, there are about 150 imprinted genes known in the mouse and about half that in humans. Genomic imprinting is an inheritance process independent of the classical Mendelian inheritance. It is an epigenetic process that involves DNA methylation and histone methylation without altering the genetic sequence. These epigenetic marks are established (“imprinted”) in the germline (sperm or egg cells) of the parents and are maintained through mitotic cell divisions in the somatic cells of an organism.
This suggests that it’s not something life-forms do, it just happens. But there are a number of mysterious terms here that need exploring – ‘a parent-of-origin-specific manner’, ‘DNA methylation’ and ‘histone methylation’.
Briefly, to get all that DNA (between 2 and 3 metres to each nucleus) to fit inside that tiny space you need some expert packaging, and that’s where histones come in. They’re proteins that DNA gets wound around, like cotton reels, and together the histones and the DNA are called chromatin. They’re also divided into sections called nucleosomes.
DNA methylation is when a methyl group, derived from methane (CH3), is added to the DNA, affecting its activity, including repressing gene transcription. Histone methylation is when methyl groups are added to amino acids in histone proteins. Again these can repress or enhance gene transcription, depending on the amino acids and how they’re methylated.
The parent-of-origin thing is most interesting to me, and needs a bit more explaining. When a human sperm cell enters an egg cell, as the first step in fertilisation, it carries its load of 23 chromosomes in what is called a pro-nucleus. In a sense a sperm cell, much smaller than an egg, is nothing but a pro-nucleus surrounded by a membrane, with a tail for motility. Once inside the egg, the tail and the membrane are shed. The egg cell also has its load of 23 chromosomes in its pro-nucleus, but this is considerably larger than the male – and the human egg cell in its entirety has about 100,000 times the volume of a sperm cell. The point is that the differences in the male and female pro-nuclei have a lot to do with epigenetic effects including imprinting, which affect phenotypic traits, including disease prone-ness and structural effects in animals and plants. Tracing these effects in molecular terms to either parent therefore becomes a priority.
So, this is a little starter in what is an overwhelmingly complex topic. I shall return to it.