MedGen

I usually rely on Nature, Science and RD.net for a lot of news, although I still have a flick through New Scientist for things in Physics that I don't have a clue about. Otherwise I try a variety of blogs such as Pharyngula and Bad Science.

True, I'm not condoning eugenics in any way, it was a sort of pre-emptive nit-pick in case anyone tried to justify eugenics on the grounds it cures diseases. Although I do think you do not give enough credit to human ingenuity by artificial selection. After all I wouldn't be able to eat grilled corn on the cob or enjoy the company of a very excitable and affectionate Labrador without it. I agree there is no substitute for the ability of natural selection at what it does, but when it comes to time scales artificial selection gets the job done fast, just a bit shoddy and without recourse to future impediments.

I think it is an issue of timescales and that annoying human trait of impatience and apathy. Some people, albeit slightly misguided IMO, do still see the world in good and bad, black and white, such that on moral grounds as soon as eugenics or human genetic modification is bought up they will make a hue and cry about it. That would be the political right, conservatives. On the other side you'd probably have the more liberal/leftist mindsets saying that it is the choice of the individual or parents of the offspring. After all who are we to deny the life of a person who would otherwise be afflicted by genetic disease or predisposition to cancer or CVD perhaps. In biological terms they all fail to realise the importance of a) natural selection doing what it does best, sorting the wheat from the chaff, and b) how long it can take for mutations/alleles to reach fixation in a population the size of the human race. Humans are lazy, they don't want to have to calculate the costs of natural selection, they want the quick fix for their problems, and bugger the rest of the world and future generations. After all it's not their problem, they'll be dead. Eugenics as a term and definition has been sullied and dirtied by its use to scientifically justify racism during the period of the 1920's-1960's. Eugenics however is not the eradication of genetic disease, it is the selection of desirable traits by another person. For a glimpse at a future where eugenics is the norm the watch GATTACA. Germ line genetic therapy for genetic disease is exactly that, the gold standard for genetic disease therapy. It is not eugenics. On a historical note it was when Galton's eugenics became popular that a lot of parents named their son's Eugene.

Well I've not finished my degree yet (just finished 2nd year, heading for a first hopefully), but epidemiology, bloody horrible. Every single graph and data set has to be statistically analysed, then you have to interpret it all using socioecomic factors, age of cases, etc. Such ball ache for nothing. Don't get me wrong, I understand the use and importance of epidemiological studies, but I really will be sticking to the molecular biosciences.

Well as E.coli has already said; we can replicate DNA in an in vitro environment using DNA polymerases, the largest application of which is that old workhorse of molecular biology, the polymerase chain reaction. Without the ability to amplify (replicate) DNA outside of cells we would not have the wonders of genomic sequencing, DNA paternity testing, DNA based forensic science. So yes it can be replicated outside of the lab, but now what's this I hear you say; "but I meant without the aid of cellular material like proteins. Ah, now this is the crux of the argument. On its own a genome is quite rightly nothing more than some DNA, but it is the potential that is contained within that makes it so important. Yours, his, mine and everyone else's genome contain all of the information require to synthesise all of the proteins we need. Further to that it also codes for all of the regulatory, metabolic and housekeeping proteins and enzyme, which themselves catalyse the wonderful metabolic reactions that keep us all alive. But it is not just proteins that are coded for, RNA does not just come in the form of messenger RNA. There are also the transfer RNA's vital to translation, the small nuclear and small nucelolar RNA's that help to form the splicesome, the ribosomal RNA that catalyses the process of translation, and finally to one of my favourites, the microRNA's that can regulate and influence various stages in the synthesis of proteins right from the start at chromatin decondensation, all the way through to translation. Wonderful thing RNA, and strangely incredibly close to DNA, if wasn't for that pesky oxygen atom missing our genomes would be an RNA based one. So how does this even relate to you speculations on the secondary importance of DNA. Well the clue is in its similarity to RNA for a start. RNA has been show to a) self polymerise under certain conditions, b) catalyse reactions that we would now consider only to be under the realm of proteins catalysed reactions and c) the ability of RNA to catalyse its own replication. Further to this we also have to consider the conditions under which RNA and DNA first arose as the prime replicators on this planet, they certainly weren't the same as today. In fact you can get a wee taster by looking for the Miller-Urey experiment (although this does not deal with DNA or RNA specifically) they show that the organic building blocks of life can be formed in a prebiotic-like environment, outside of a cellular context. See a pattern emerging here. So your supposition that DNA cannot replicate itself outside of the cell meets its final stumbling block in the shape of fidelity. Fidelity is how well something replicates itself, or is replicated, without changing. In DNA these changes are referred to as mutations. Now we can expect that when the first prime replicators arose there were many numbers of different molecules that could self replicate, however it was the ability of DNA (or RNA as is thought among many biological circles, I'm undecided personally as the verdict is still out on that one) to replicate itself with a high fidelity. In a cell there are many mechanisms that have evolved to deal with any problems in copying fidelity, that is why such a large amount of energy is devoted to DNA repair mechanisms and the proofreading during and immediately after to prevent detrimental mutations. When there were no cells I imagine that this wasn't exactly a necessity, something that arose as a later adaptation when the vehicles started to become more than just micelles and simple lipid bilayers. Actually this supports its role as a molecule for holding genetic information, even then it may stable as in not highly reactive, but as E.coli has already pointed out DNA can be sheared and nicked simply by stiring it (has its pro's and cons depending on what you're doing with the DNA). Even when DNA is "acted upon" (whatever that is supposed to mean) it remains stable, yes you do not want a molecule that stores information to be highly reactive. Blimey if the primary composite of our genetic material was made of caesium I doubt we'd exactly be around long to post on forums about it. Well it's a shame that you view DNA in this way, once again to ape E.coli's sentiments; go and read about biochemistry, molecular biology and genetics, you never know you might learn something.

Thankyou, I aim to learn always and educate where I can, glad to be of help.

The point is that DNA is the replicator, life is a series of replications (a generation). At the end of the day the cells and organisms that carry the DNA are in fact just vehicles for the DNA. I would suggest reading Richard Dawkins The Selfish Gene if you have not already. Firstly red blood cells do not replicate, therefore they have a finite lifetime (about 120 days max IIRC). They are differentiated from haematopoetic stem cells in the bone marrow. So the fact that they have no nuclear DNA is neither here nor there, they do not replicate. In fact their purpose does not require the presence of nuclear DNA, they are formed with the requisite cell components and sufficient proteins for their short lifetime. Even then if they become irrepairably damaged then they can undergo apoptosis. Great, but what you fail to realise here is that prior to mitosis there are several complex checkpoint pathways that initiate cascades of gene expression for the regulatory proteins for before, during, and prior to replication. The fact that eukaryote DNA is tightly packaged into heterochromatin is because of its size. In every human cell there is around 2m of nuclear DNA split between the 23 pairs of chromosomes, to replicate that much takes a long time for a start. But also to avoid massive loss it is required to be tightly packaged so that it can be passed onto the daughter cell. This also falls apart when you consider this in the context of bacteria, they do not package their DNA, in fact they do have actively expressed genes during replication. The cell only provides the enzymes as a result of direct transcription, followed by RNA modification and transport from the nucleus, then translation by ribosomes, finishing with any post-translational modifications. So lets see where this starts, oh that's right with the genes that code for the various enzyme subunits. So you mean when the cells are dividing? See above. The cell has nothing in mind, it is not sentient, it follows certain pathways depending on stimuli and signals from its environment, then reacts accordingly. Bad analogy, why? A cell is not a computer and DNA is not a hard drive, nor is it a blueprint. What it is however is more like a recipe, it gives a list of the requisite ingredients, but does not provide them directly. It can indirectly provide some of the tools and certainly provided the control points and regulatory elements in the shape of proteins via transcription then translation, but also microRNA's are a major regulatory element in a cellular environment. When it comes to adding genes to a cell it has to be beneficial else the cell will reject and degrade it. This is one of the basic tenets of cloning in a lab, if you want to add a new gene to a bacterial or yeast culture then it has to give it an advantage in some manner. Overall you fail to understand what DNA actually is, it is the prime replicator. It does not care for your feelings or how you interpret its functions with bad analogy, it simply is what it is. It provides the information for synthesising proteins, which keep the cell running. For a cell to divide/replicate/reproduce then it needs its prime replicator. A cell without DNA is doomed to die in a natural environment.

It may well be cell/tissue specific that results in the locale of this gene being expressed. Different cells in different tissues express different genes, it's one of the reasons there is cell differentiation, and that life isn't just an amorphous blob of cells like bacteria.

Although not technically an immunological response to an invading pathogen many organisms have either native intracellular mechanisms or secreted extracellular ones. Whether this extends to plants I don't know but I wouldn't be surprised if they do have an evolved immune response mechanism. For instance; one of the key tools in molecular biology, restriction endonucleases are derived from bacteria as a line of defense against invading phages. Additionally there is the non-specific antimicrobial lysozyme secreted in saliva and chicken egg white. Seeing how lysozyme is prevalent throughout the animal kingdom I would not be surprised if it is a primitive form of innate immunity. As for adaptive immunity I expect that it is a later addition to complex multicellular life.

Well for a start it depends on whether the disease is multifactorial (i.e. multiple genes contributing to a single phenotype), or whether it is a simple Mendelian inherited disorder such as Huntingdon's. For multifactorial diseases that have a major genetic component such as familial inherited cancer or heart disease then there is no doubt that what lifestyle you lead will have an impact on the outcome of a genetic disorder, i.e. not a cut and shut case. A lot of the classically single gene disorders have been elucidated and many of the mutations that cause them. Nowadays a lot of research into genetic disease focuses on these multifactorial disease, which because they have a massive environmental component, are much harder to unwravel. So potentially there are ways of avoiding these diseases, but not for certain until all of the factors and pathways involved have been elucidated. Hope that helps answer your quesiton, and don't worry about seeming ignorant, you have come to the right place to ask questions regarding science.

Behe is the man that pointed at a bacterial flagellum and shouted Goddidit! I question his validity as a scientist on the grounds that he has discreditted himself merely by associating with the DI propagandists. As for the 44,000 generation E.coli experiment, they actually took culture samples something like every 500 generations so they could backtrack and pinpoint the timings of the individual mutations that lead to the aerobic citrate metabolism. Good blog by Grrlscientist

I'm not sure what you mean by multiple inheritance here. Are you referring to autosomal linked heritability perchance? Where by genes are inherited in tandem beacuse of their physical location on the chromosome? As for sex-linked, this refers to genotypes or phenotypes that occur in specific patterns beacuse they are located on the sex chromosomes. IIRC thorax colour in Drosophila melanogaster is an example of a sex-linked phenotype, as is haemophilia in humans.

I have a conjecture (take note of that word Vexer), that it is a) a case of the "me too" phenomena often seen in research and journal publishing, b) people are no longer afraid to speak out about being atheists, and c) the rise of fundamentalist religious sects in recent decades has warranted a response from the secular side of the world. Thats my 2p any way.

According to IUBM enoyl-acyl carrier protein reductase is EC 1.3.1.9. If that is correct then it states that the substrate is 2,3-enoyl ACP and the product is acyl-ACP. However according to Berg et al (2007) the reaction in bacteria is: Crotonyl ACP + NADPH + H+ -> butyryl ACP + NADP+

It exists in this universe, that pretty special, and for all we know it could be the only life in this universe, although I doubt that supposition to be true.

I've been given this question as a part of a revision tutorial. I've already done the calculations but was wondering if anyone could point out any glaring errors. This is not an assessed piece of work, so strictly not homework per se. The turnover number of carbonic anhydrase: Carbonic anhydrase of erythrocytes (Mr 30,000) has one of the highest turnover numbers among known enzymes, it catalyses the reversible reaction of CO2: H2O + CO2 -> H2CO3 This is an important process in the transport of CO2 from the tissues to the lungs. If 10μg of pure carbonic anhydrase catalyses the hydration of 0.30g of CO2 in 1min at 37°C at Vmax, and the reaction volume is 1ml. What is the turnover number (Kcat) of carbonic anhydrase expressed in units of per min and per sec)? Mr of CO2 is 44. So here are my calculations: Kcat = Vmax/[E]t, where [E]t is the total enzyme concentration in M or mol/ltr. Vmax is the at which all active sites are fully saturated. This is given as 0.30g after 1mins. Reaction volume=1ml Protein content = 10μg Therefore [E]t is 10μg/ml, this needs to be expressed as M or mol/ltr. M=g/ltr x mol/g So carbonic anhydrase Mr = 30,000 or 30,000g/mol. Take the reciprocal = 1/30,000 = 3.3E-05. There are 10μg/ml of volume, so convert to g/ltr = 0.01,. Now [E]t = 0.01 x 3.3E-05 =3.3E-07 mol/ltr or M Vmax= 0.30g in 1mins in 1ml. Mr CO2 = 44, [CO2] = same base calculations as [E]t. (calculating mol/ltr) =0.068mM So Kcat=Vmax/[E]t =0.068mM/3.3E-04mM =204 mM per sec and =12240 mM per min.

Ah, but the common misconception here is that it is the gene that is good or bad. Technically it is the allele for that loci that may result in a deleterious effect, particularly with respect to homozygosity. As previously mentioned this is very much the case with the sickle cell allele. Heterozygosity (sickle cell trait) effectively confers a selective, and thus reproductive, advantage because it confers considerable protection against malarial infection. However, homozygosity is severely detrimental to the carriers health because it results in sickle cell anaemia. This is the cost of natural selection by balancing the advantages and disadvantages of an allele. As a result of its effect it is highly unlikely that it will ever reach a 100% frequency within a population as natural selection will continuously weed out the homozygous carriers. Unfortunately it is not always as simple as this as. There are many alleles that may confer a selective advantage where heterozygosity occurs at a loci, in 2005 this was highlighted by a study into the possible effects on intelligence of the Tay-Sachs causing allele within Ashkenazi Jewish populations. Once again because it is a recessive condition heterozygosity provides a sexually selective advantage where increased intelligence is desirable. Natural History of Ashkenazi Intelligence Although this paper is highly controversial and no further evidence has been forthcoming, it merely highlights the possibility of such correlation and selective advantage occuring. As for the case of Huntingdon's this is the result of an insertion of a VNTR (variable number tandem repeat), I forget exactly what the sequence is, but because it does not present until after reproductive age it is passed on to its offspring, therefore it can be considered as being selectively neutral. Now if a diagnostic tool is created that can screen for, and eventually correct, these VNTR's then the allele frequency will fall quickly with a few generations. I think many people often overlook the importance of neutrality and genetic drift and tend to concentrate solely on what is selectively advantageous. Note I am not disputing selection pressure, merely that it is most definitely not the whole picture.

Mitochondria themselves replicate autonomously, they are not dependent on the cells replication/division. It's one of the reasons that certain cell types are paced full of mitochondria, whilst others have only the required amount. This also tends to be reliant on the ATP requirements of the cells they are contained within. Cells are not "aware" in the sense that you or I are, however they are capable of signalling chemically and electrochemically to each other, and even within the cell there are significant signalling pathways that can elicit various responses. Nuclear DNA is the what is often referred to as the genome, all though this is strictly a misnomer because mtDNA should be included, even though it is fully independent. Mitochondria however not fully independent (hence the semi-autonomous replication) because they rely on some of the nuclear DNA genes to function properly.

Terribly sorry, the explanations so far have been very simple, I thought perhaps that Vexer was at least at the level of the interested layman, re-reading this thread and I think I regret that assessment.

That strictly is not true, as given in the example of parental inheritance of mtDNA published in the New England Journal of Medicine, sperm cells do contain mitochondria. However, they are localised to the area of the cell near the flagella, seeing as this is the site of highest ATP requirement in sperm cells. During gamete fusion it is the nuclear DNA that is transfered to the egg, which additionally contains all of the requirements for the first few days of cell division (note not strictly the same as mitosis, one of the other reasons egg cells are so large). This is exemplified in the above journal article where the paternal mtDNA was located solely in the patients skeletal muscle IIRC. The importance of localisation during cell division is underestimated, particularly when pertaining to stem cell differentiation.

I might possibly add that genomic imprinting is an evolved epigenetic mechanism, as a way of preventing overexpression from duplicate genes. E.g. the differential imprinting of Igf2 and H19 in many mammals, including humans and mice.

I would also add that it depends on a) where the gene in question is expressed (the cell type), b) what the effect in said cell type is and c) the level of expression, whether it is basal or cell specific and thus a higher level of expression. Additionally you may have alternative exon splicing depending on which cell type the product is being in expressed in if it is a protein product rather than a functional RNA. You also have to take into account the complex interactions between the gene products within the cell and how they respond to cellular signals. It definitely is not a case of one gene for one trait.

I was quite impressed with the actual article in the print version of New Scientist, considering it is normally lay people interested in science that read it. A little bit of conscious raising for evolution is always good, not something that is readily available in journals such as Nature and Science, and a lot more accessible.

Howdy all, I've not had a decent flick through the forum yet, but I thought it prudent to at least introduce myself first, manners can be terribly annoying at times. I'm a second year undergraduate in Medical Genetics in the UK, and I must say its all rather interesting this science malarkey. Current interests on the science side of things are gene expression, epigenetic modifications in cancer (got to love those methylated CpG's), cell signalling pathways and I've just started to look into the adaptive immune system a little. Biology has fascinated for many a year, hence I'm now reading for a degree in the bloody thing! Lots of mysteries still to unsolve but without all that tedious mathematics and such (maths isn't exactly a strong point for me). Well thats my little introductory ramble, so howdy all and I look forward to supplementing my studies with some expert insights from other members. Mike