Athletes: nature vs. nurture? Having watched a lot of olympians the last few weeks, I was struck by how many of them have actually spent their wholes lives/careers training for their one event (be in running a marathon, or throwing a javelin). This is of course unsurprising - a lot of people take their sport very seriously - but I wondered to what degree these athletes are predisposed to becoming atheletes, and to what degree they just 'happened' to end up doing it.

I've had a bit of a search around, but have been unable to find any studies (although there is an awful lot of media attention to the topic) that actually study the interaction between nature (genetics) and nurture (environment/training etc) in the context of top-end athletes.

It is quite clear to me that the answer is of course 'both', but to what degree? Have any common genetic variants/loci been identified, or is 'athleticism' a far too complex trait for this? Thanks.

For all types of athlete, their ability is determined by both genetic and environmental factors (nature and nurture). The degree to which each contributes ultimately depends on the demands of the sport.

As an example let's compare basketball and golf.

Basketball is likely to have a strong genetic component because players tend to be exceptionally tall (average is over 2 metres and there are only a handful who have played NBA under 1.75m). Because height is strongly genetically (but not entirely) determined by the genes, they have a big influence on whether someone can poses the physical qualities to play in the NBA. However, a large part of their technical capabilities are due to their environment. If you give a basketball to someone who has played 2 games a week their entire lives and ask them to take 10 shots it is likely they would score more than someone who has never seen a basketball!

Comparing basketball to golf, there are all sorts of body types within the PGA tour, and they is no/few obvious genetic traits which golfers tend to have over other people. This would suggest that golfing ability is more affected by environment.

So an easy way to get a rudimentary test of genetic contributions to sporting ability would be to compare frequency distributions of focal traits in the athletes to distributions of regular people. Obviously the phenotypic trait you measure has both genetic and environmental contributions (e.g. childhood diet) which could affect them but it would be a good starting indicator which could give some candidate traits to test.

As a scientist I would also consider sequencing some athletes and some non athletes and seeing which genes the athletes have more often then the regular person's genome. However, such studies are likely to be complex - linking phenotypes (in polygenic traits) to the single allele variants relies on large sample sizes. Generally it will be more difficult if:

There is large variance in the trait
The gene has a small effect (see major and minor effect genes)

Both of these problems going to be positively correlated with the number of genes affecting a trait (how polygenic is it?) which for athletic ability is probably quite a substantial amount of genes.

EDIT:  Here are some possible studies for your further exploration of the topic-

Candidate genes for Specific Genetic Markers of Endurance Performance and o2max

Rowers have an excess of the ACE I allele

Elite Italian footballers with "explosive" leg strength also reveal ACE and other genetic markers

A precautionary tale about Genetic tests for athletic ability

I don't think this will ever be answered, mostly because studying the long-term effects of athletic training is very difficult. People constantly change their training methods, habits, and schedule, so controls are nearly impossible to construct.

My opinion, is that the nurture component is the strongest, because of the amazing plasticity of the body in response to stress: bones grow/reform differently, neural networks become trained, muscles change. Over many years these can be enormous. This is true of all humans, absent those with severe genetic faults.

Genetics probably has a stronger influence on the psychological traits which might induce someone to train so hard. Though parenting could certainly override this.


Do all cells produce the same proteins? If DNA is more or less the same in all cells, and DNA is used to produce proteins from aminoacids, then do all cells produce the same proteins or are they specialised/controlled by something?

Each cell will indeed have the same DNA sequences and ability to produce any given protein. However, there are certain factors (transcription factors) and cellular conditions within a cell that dictate which proteins are produced. If the conditions are right then only certain proteins will be produced depending on what type of cell it is. This process by which a cell continues to express selected proteins and becomes specialized for a specific function, is called differentiation. Expression of proteins that are not required can be prevented by transcriptional repressors (or by epigenetic mechanisms such as methylation of DNA sequences). So to answer your question, while cells contain the instructions (DNA sequences) to produce potentially any protein, not every type of protein will always be produced.

Keep in mind that my answer is very basic; the answer isn't as simplistic as I'm making it out to be.

In a simplistic sense DNA can be viewed as more or less the same amongst species, but with a variability of say 0.2% between humans and chimps that might not seem like much, but it really is. A human genome is over 3 billion bases long, which means that 10s of millions of bases are different between humans and chimps and every three bases encodes an amino acid that then become one piece of a protein.

As such there is a high degree of variability in the proteins expressed in a given cell. There are many homologous proteins between cells/species, which are proteins translated/transcribed from variable DNA/mRNA sequences, but ultimately serve the same function. Additonally, even though all human cells have the same genome (within the same individual), specialized control and compartmentalization of the genetic code (DNA) is why we have different organs and tissues such as the heart, skin, and lungs.


What is the effect of non-vaccinated people on vaccinated people? Many times have I heard that anti-vaccine people are dangerous even to the vaccinated population. Is that true? If so, how can it be? People say that germs will attack them, and soon they would eventually grow and spread even toward general population which actually got its vaccines.

I mean it's so counter-intuitive: if I'm vaccinated even when disease will spread I shouldn't be in danger.

Biology is rarely black or white, all or nothing. Protective immunity is generally not an on/off switch, where from the moment you're vaccinated you're infinitely resistant for the rest of your life. You shouldn't expect that, having received a smallpox vaccine, you could have billions of smallpox viruses squirted directly into your lungs and shrug it off without noticing.

Given that (fairly obvious) fact, you should immediately think of scenarios where vaccinated people are still at risk of disease following exposure to unvaccinated people. What about older people who were vaccinated 20 years ago, 50 years ago? What about people whose immune systems are slightly weakened through lack of sleep or obesity or stress? Any of these vaccinated people might well be protected against a brief encounter, but not against, say, being in an airplane seat for 18 hours beside an infected child shedding huge amounts of virus, or caring for their sick child.

It's all sliders, not switches. You can have a slight loss of immunity (4 hours sleep last night) and be protected against everything except a large exposure (your baby got infected and won't rest unless you hold him for 8 hours). You can have a moderate loss of immunity (you were vaccinated twenty years ago) and be protected against most exposures, but you're sitting next to someone on the subway for an hour. You may have a significant loss of immunity (you're a frail 80-year-old) and still be protected against a moderate exposure, but your grandchild is visiting for a week.

Think of every human being as being a walking petri-dish, full of growth medium. When you grow a large colony of micro-organisms, you are allowing that population to experience a larger number of mutations. Every mutation is one more potentional strain that can beat the defenses of our immune systems, even those provided by vaccines. So, if you don't get vaccinated, you are potentially providing safe harbor to the micro-biological parent of the next vaccine-resistant/anti-biotic-resistant super-flu.

This same principle is why large super farms are so dangerous: huge numbers of animals provide more opportunities for micro-organisms to experience mutations that allow them to infect more resistant hosts. The fewer hosts that a micro-organism  can infect, the lower the number of opportunities for mutation.

This is one facet of the issue, among those others have mentioned.


Why do only humans commit suicide? Why is it that only humans commit suicide?

Many animals do 'brave' things to protect their children or family, and some male spiders sacrifice themselves so that they can impregnate the females. However, humans commit suicide without necessarily any intention to help their offspring. Why?

Animals can hurt themselves to save their life for example foxes and tigers falling in traps are known to chew their paws to escape from the trap. Thus one can argue that all living creatures want to live and to escape death as well as losing freedom.

looking at how animals live, an animal can always use its capabilities to escape danger or problems as well as to look for food for survival. In humans who commit suicide sometimes it is because  there is no "exit". for example some people commit suicide due to being unable to pay their loans it is the feeling of distress losing all hope and the fact that it is hard to escape from problems in a human society that lead to this thinking.

so a person doing so is trying to escape the problems instead of facing them. further, the fact that humans have the concept of "responsibility" and being held accountable by members of the society all these lead to this thinking as the only escape


Is natural selection a tautology, and therefore not truly falsifiable? I've heard the argument from a lot of creationists that all the evidence for natural selection (and by extension, evolution) in general is worthless because natural selection is so flexible that it could cover all the data, no matter what we discovered. In essence, that natural selection is a tautology:

Survival of the fittest. What is 'fit'? What survives.

There are other creationists, however, that admit that natural selection could be falsified. These are split into two groups:

The ones that say, if you rephrase natural selection as a non-tautology, it becomes obvious that it doesn't work:

  Natural selection has been criticized as a tautology. This would be a major problem for evolutionary biology, if true, because tautological statements can't be falsified and, therefore, can't be scientific. There is merit to this critique insofar as the theory of natural selection is indeed generally described in a tautological manner. However, natural selection can be described non-tautologically if we’re careful. Natural selection should be defined as the theory that attempts to predict and retrodict evolutionary change through environmental forces acting upon organisms. However, this re-framing comes at a cost: it reveals, based on our current knowledge of evolutionary forces, the lack of ability to make accurate predictions about expected changes except in the most simple of circumstances.

And those that say that the falsifying options provided by natural science are impossible to actually use. Here are some of those falsifying options:

  Charles Darwin himself proposed a rather strong test of evolution: "If it could be demonstrated that any complex organ existed, which could not possibly have been formed by numerous, successive, slight modifications, my theory would absolutely break down." [Darwin1859, pg. 175]. This is the basis of claims by various intelligent design writers that various biological structures, such as the vertebrate immune system or the bacterial flagellum, are "irreducibly complex" -- they consist of multiple components that could not develop in the absence of the others. However, these structures have been exhaustively studied in the scientific literature, and scientists have demonstrated entirely plausible evolutionary pathways. See Complexity.
  Famed biologist J. B. S. Haldane, when asked what evidence could disprove evolution, mentioned "fossil rabbits in the Precambrian era" [Ridley2004, pg. 66]. This is because mammals, according to current scientific analysis, did not emerge until approximately 40 million years ago, whereas the Precambrian era is prior to approximately 570 million years, when only the most primitive organisms existed on earth.
  Biologists had long conjectured that human chromosome number two was the result of a fusion of two corresponding chromosomes in most other primates. If DNA analysis of these chromosomes had shown that this was not the case, then modern evolutionary theory would indeed be drawn into question. This "fusion hypothesis" was indeed confirmed, rather dramatically, in 1993 (and further in 2005), by the identification of the exact point of fusion. For additional details see DNA.
  Modern DNA sequencing technology has provided a rigorous test of evolution, far beyond the wildest dreams of Charles Darwin. In particular, comparison of DNA sequences between organisms can be used as a measure of relatedness, and can further be used to actually construct the most likely "family tree" hierarchical relationship between a set of organisms. Such analyses have been done, and the results so far dramatically confirm the family tree that had been earlier constructed solely based on comparisons of body structure and biochemistry. For additional details see DNA.

Is there any way to save natural selection? To do so, we need to:

Prove it can be explained non-tautologically
Prove that it does make useful predictions
Give falsifying experiments that are reproducable and actually possible.

I think @Remi.b's answer is great and really the only way to answer your questions is with a comprehensive introduction to evolution. However, I wanted to address the tautology issue more directly.

First, the "survival of the fittest" seems like a tautology with "natural selection" because it is not a description of how natural selection works, rather, it is a phrase meant as a synonym for natural selection, to help describe the result to someone unfamiliar with the phrase.

Let me use an analogy: it would be like if you were a very new learner of English, and I told you "Joe's truck has more mass than an elephant!"

If you aren't really familiar with the term "mass" in English, this phrase could be confusing. So I explain instead that "Joe's truck is heavier than an elephant." If you know the word "heavy" this is easier to understand.

However, there is a tautology there! the car is actually heavier because it has more mass, but that does not make either phrase untrue or untestable: it's just another way of saying the same thing within a context (i.e., those statements are the same if they are exposed to the same gravity).

The testable hypothesis that natural selection makes is that, given 2 things: 1) a population where individuals have traits that give them different chances of survival, and 2) some way for offspring to inherit traits from their parent(s), then the population over time will consist of individuals who are more likely to possess the traits that gave a high chance of survival.

Following this, should the environment change in some way such that a different trait is now beneficial, that trait will increase in prevalence.

There are way too many experiments to summarize here that show 1), 2), and a combination of 1) and 2), as well as experiments that show that indeed, when you have 1) and 2) you get natural selection.

The "survival of the fittest" statement which Darwin recommended as the best formulation of his idea of "natural selection" is definitely a tautology because there is no other operational definition of fitness besides survival (or reproduction). So, survive (reproduce) are those who survive(reproduce).

Darwin naively attempted to imitate the process of selection of domesticated species assuming that new species are produced by "natural selection" in the same way as dogs are produced from wolves. The poor guy was probably not familiar with the facts: the species produced by selection are inferior to the original ones. Dogs are inferior to wolves since they lost a lot of vital features. Moreover, this loss of information is irreversible: you cannot produce a wolf from a spaniel by selection.

In an abstract form, it is quite simple. There is a law: the complexity of a result of a selection algorithm cannot exceed the complexity of the algorithm. Therefore, any selection results in the information loss, and no new information can be produced by selection.


Why do so many parasites infect definitive and intermediate hosts rather than just one host? Many parasites infect multiple host species, with one host species being the definitive host (where the parasite reproduces), and the other host species being the intermediate host (where the parasite grows to maturity). (Further details described as "complex life cycle" at https://en.wikipedia.org/wiki/Parasitic_life_cycle ) Why is this complex life cycle so common? Why wouldn't more parasites adopt a simpler life cycle of just one host?

I knew that there were some parasites that infected more than one kind of host species, but now that I am looking into it, it seems like a majority of internal parasites have this kind of life cycle. Does anyone know why?

Several reasons have been proposed.

  We suggest that complex cycles in helminths without penetrative infective stages evolve by two essentially different processes, depending on where in the cycle a new host is inserted. In ‘upward incorporation’, a new definitive host, typically higher up a food web and which preys on the original definitive host, is added. Advantages to the parasite are avoidance of mortality due to the predator, greater body size at maturity and higher fecundity. The original host typically becomes an intermediate host, in which reproduction is suppressed. In ‘downward incorporation’, a new intermediate host is added at a lower trophic level; this reduces mortality and facilitates transmission to the original definitive host.

--Evolution of complex life cycles in helminth parasites

  Despite these advantages to omitting hosts, the majority of digenean trematodes have a life cycle with three hosts, suggesting strong counteracting forces that maintain hosts in the cycle. Such forces have been proposed to be higher growth and fecundity (Parker et al., 2003), an increased probability of finding a mating partner (Brown et al., 2001), and higher transmission rates (Morand et al., 1995; Choisy et al., 2003; Parker et al., 2003). ... we propose here that maintaining a second intermediate host in the life cycle can be advantageous for the individual parasite to increase the intermixture of different clones and therefore decrease the risk of matings between genetically identical individuals in the definitive host.

--How a complex life cycle can improve a parasite's sex life

Also see The evolutionary ecology of complex lifecycle parasites: linking phenomena with mechanisms.

I assume that by internal parasites you mean animals like tapeworms etc?

They can infect several species simply because they are not picky. These parasites do not rely on precise molecular hijacking mechanisms like intracellular parasites (e.g. Apicomplexa).

All they need is a certain amount of heat and humidity (which any host provides) and food pre-digested by the host, which is essentially the same for host species that share the same feeding habits, so there is no reason a priori for them to have a narrow range of hosts.


Hayflick's limit and cell division Suppose the Hayflick's limit of a cell is 10 and it divides 10 times.  At this point, it undergoes differentiation.  Is it possible for it to undergo dedifferentiation at this point?

I don't think so naturally. I think the general stream of the progeny goes stem cell => pluripotent cell => progenitor cell => specialised cell.


Is variation a result of Evolution? We know that the DNA copying mechanism that replicates DNA during cellular division is not 100% accurate and the resultant errors are the source of variation in the members of a population.

At the same time, we are also aware of the benefits of variation - how it is useful in ensuring the survival of a species over time and leading to evolution.

I would however like to know if 100% accurate DNA replication is possible (even if hypothetically) - because in my opinion, organisms can surely survive (atleast individually) without variation or evolution.

If it is so, is it possible that organisms with 100% accurate DNA replication did exist, but eventually their populations died out (due to natural selection) and we were left only with organisms that showed variation?

Putting in simpler terms, it is possible that evolution itself is the cause of variation that now causes further evolution?

There is previous research for that field of macroevolution.... Horse shoe crabs change slowly and tropical fish change fast.

You are right, it's not just random variation, it's fine tuned by DNA transcription processes which are too developed to be random, so the complexity of the processes leads scientists to think "WTF" regarding epigenetics, transgenerational phenotypic plasticity, paramutation, genetic drift, DNA mutation types, Specifically: "no systematic cross species studies of variation have been conducted (most focus on model organisms)", because the topic is so intense.

You don't have to change the DNA code of alleles to go from a chimpanzee to a human, most of the changes come from pre-existing genes that are varied to produce different results.

The texts for macroevolution fine-tuning of variability talk about: variability, gene flow, constriction, epigenetics, of traits of adaptive significance, of DNA mutations, their mathematical measurement... it can be summarized by this statement:

" variability has been a dilemma of evolutionary biology. Considering the pattern of increased genetic variation associated with environmental clines and heterogeneous environments, selection in heterogeneous environments has been proposed to facilitate the maintenance of genetic variation. No comprehensive models have been developed, likely due to the genetic and environmental complexity of this issue. " ref

Many books are devoted to the subject, so there is lots to read through, and there are mutation-control systems that fine tune variability, so it gets complex:

"... Epigenetic modifications, such as; DNA methylation, together with covalent modification of histones, are thought to alter chromatin density and accessibility of the DNA to cellular machinery, thereby modulating the transcriptional potential of the underlying DNA sequence" ref

There are genetic switches, which vary which DNA sequences are expressed by different species... Humans and chimps are 98% the same, and genetic switches can change the species selectively without having to change the DNA itself... "regulates when and where genes are turned on and off and how much protein they produce. The regulatory machinery works when proteins called transcription factors bind to specific short sequences of DNA that flank the gene, called transcription factor binding sites, and by doing so, switch genes on and off." ref

sharks ahve less less variability than humans and 1.5 times bigger genome...
"The researchers found that the white shark genome contained a lot of genes responsible for maintaining genetic stability — things like DNA-repair genes and tumor-suppressing genes. And when the researchers compared the white shark's stability genes with analogous genes in other vertebrates, they found small changes in the gene sequence that suggest a specific pattern of evolutionary adaptation for these genes in white sharks."

Only a few epigenetic processes for transgenerational epigenetic inheritance have been discovered, which vary species traits independently of the DNA sequence, so we don't even know how they compare between animal families.

Is variation a result of Evolution?

No, you're putting the cart before the horse & mistaking cause for effect.

Variation is the result of mutation (whether caused by copying errors, radiation or whatever).

Evolution is the result of variation.

Mutation > Variation > Evolution

Evolution is merely the winnowing process by which more beneficial variations (as in terms of fittest to survive in the existing environment, which includes competition from other variations) 'succeed' & less beneficial ones don't, it doesn't cause the variations.

Variation can happen without evolution but evolution can't happen without variation.


The human has 46 double chromosomes or simple chromosomes? What I mean: does the human cell have 46 of these:

or 46 of these:

Thank you in advance.

Your first picture shows a chromosome that has been (1) condensed and (2) undergone DNA replication. During G1 interphase (normal cell activity; not dividing), your chromosomes actually do not look like either of the pictures. They look more like a mass of noodles (called chromatin; look at the image provided below); it is only during prophase (step 1 of mitosis, where the cell undergoes division) that the chromosomes condense into the form you have depicted in picture 1. Now, in G1 interphase, you only have single chromosomes. You have 46 of these, which can be grouped into 23 pairs—23 from your father, and 23 from your mother. Remember they aren’t condensed during this stage.

I have also included a diagram of the cell cycle:

In S interphase, DNA undergoes replication, and each of the 46 chromosomes create a double. This double sticks to the original chromosome at a point called the centromere. So long as the two “chromosomes” are conjoined at the centromere, the two “chromosomes” are considered as one chromosome, consisting of two sister chromatids (each like the “single chromosomes” you had previously). Again, in S interphase, chromosomes are not condensed, and look more like noodles than either one of your pictures.

During prophase, the chromosomes look like picture 1. Picture 2 depicts a sister chromatid during prophase (and metaphase), which is considered a chromosome after anaphase (when the two sister chromatids are separated from their centromere). Remember that when the chromatids are not conjoined at the centromere, they are considered each as their own chromosome.

Thus, the human body always has 46 chromosomes. They are “double chromosomes,” as you call them, during S phase of interphase to the beginning of anaphase of mitosis. They are “single chromosomes” from anaphase of mitosis to the beginning of S phase of interphase. As most cells spend the most time in G1 interphase (normal activity), you can say that most of the time their chromosomes exist as single chromosomes. Again, note that most of the time they don’t look like your pictures, except for the times that I mentioned above.

EDIT: To answer the question in your comment:

  If during interphase the DNA is not yet condensed and looks like a mass of noodles, then how can we know that there are 46 chromosomes (single ones in this case)?

During interphase, it is indeed difficult to tell how many chromosomes there are. It is only when they condense that they become visible to the eye and can be observed through a microscope. Chromatin, in its noncondensed form, is considered as euchromatin—that is, true (noodly) chromatin. When it is condensed, it can be referred to as heterochromatin. We can only count the number of chromosomes when they are in heterochromatin form; euchromatin is invisible to us. If we align all the chromosomes present, we will get something called a karyotype. Look below.

(You can see each chromosome in each of the 23 pairs are “double chromosomes.” These chromosomes were likely documented during prophase. Some karyotypes show "single chromosomes," most likely taken during anaphase or early telophase.)

In any case, double or single, we can observe that there are 46 chromosomes at all times. If we see "double chromosomes," we would find 46 chromosomes. If we see “single chromosomes,” we would still find 46 chromosomes. In both cases, we would find 46 centromeres, and ergo, 46 chromosomes.

References

Reece, Jane A., Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, and Robert B. Jackson. "The Cell Cycle." Campbell Biology. 10th ed. Glenview: Pearson, 2014. 232-50. Print.
https://micro.magnet.fsu.edu/cells/nucleus/images/chromatinstructurefigure1.jpg
http://www.everythingmaths.co.za/science/lifesciences/grade-10/03-cell-division/images/d62a6708a4a3942f21e003500ddf9664.png
https://study.com/cimages/multimages/16/karyotype_karyogram.png

Answer: Both are images of chromosomes. Before a cell divides, we have 46 structures of Image 1. After cell division, we have 46 structures of Image 2 in each daughter cell. They are structures of chromosomes at different phases of cell division.

When the human cell is not dividing we have Interphase, during which chromosomes inside the nucleus look like a network of threads, called chromatin.

Cell division takes place in four phases,abbreviated: P-M-A-T

Prophase: during which stage the chromatin condenses and duplicate themselves. each of this is two chromatids attached at the centromere.

Metaphase: the chromosomes align themselves at the equator
Anaphase: The chromosomes are pulled towards the two poles, each at opposite ends of a cell. Each of this is a single chromatid.

Telophase: contractile ring (a cleavage) starts to separate the two daughter cells.


Relationship Between Evolution and the Increase of Entropy of Earth I was confronted by this question:

Biological evolution of life on Earth, from simple prokaryote-like cells to large, multicellar eukaryotic organisms,

A) has occurred in accordance with the laws of thermodynamics.
B) has caused an increase in the entropy of the planet.
C) has been made possible by expending Earth's energy resources.
D) has occurred in accordance with the laws of thermodynamics, by expending Earth's energy resources and causing an increase in the entropy of the planet.
E) violates the laws of thermodynamics because Earth is a closed system.

Answer:  A

However, I do not understand. Biological evolution does cause the system (living organisms)'s entropy to decrease. So, by the second law of thermodynamics, the entropy of the universe (in this case Earth), must have overall increased.

I would answer D... Where am I going wrong?

However, I do not understand. Biological evolution does cause the system (living organisms)'s entropy to decrease. So, by the second law of thermodynamics, the entropy of the universe (in this case Earth), must have overall increased.

The universe and the earth are not equatable. Earth is not an isolated system. Life causes entropy of the earth to decrease. This is offset by increased entropy of the sun, which is the primary source of energy for the earth. Overall, the entropy of the universe increases.

Evolution increases complexity (entropy)
e.g., developing a new citrate path way in E. coli

It does this process by of expending energy.
i.e., via lifeforms's metabolism

So to answer your question:

A,B,C are all correct (or part of a correct answer)

However D is the most correct answer (It is an all of the above type answer)

E is a none of the above answer (and most incorrect)


New earliest life found, what are the implications? So a couple of days ago it was announced that new fossils of microorganisms were possibly discovered around former hydrothermal vents. According to the paper these fossils "are at least 3,770 million and possibly 4,280 million years old" making them the earliest instance of life found so far. If the upper estimate is correct that would mean these organisms existed "only" ~250 million years after the formation of Earth.

Does this discovery shake up any of our previous ideas and/or provide new insights about the earliest life?

Not a lot, the sample is not conclusively biotic in origin nor is it necessarily much older than known fossils, 3.7 billion vs 3.5 billion. The sample is a few simple hematite filaments, complex hematite filaments do form as a byproduct of oxygen using (aerobic) bacteria, they can also be formed by metamorphic processes. Subscribing these filaments to life and proposing oxygen must have been present far earlier than any evidence supports based on this is wishful thinking at best.

If it were correctly identified and as old as possible it would have only a small effect, it would make finding life on other planets more likely becasue it would mean life forms basically as soon as you have persistent liquid water. It might indicate oxygen earlier than suspected but that seems unlikely.

The effect of this hypothetical discovery (because I haven't seen the dating of the rocks yet) is almost non-existent. It just reinforces an idea already present in the origins of Life community for a lot of time-you discover life as soon as you discover solid rocks capable of creating fossils, so Life must have originated immediately after the cooling of the Earth's surface or possibly it simply originated elsewhere in the Solar system and was transported here by meteorites (there is solid evidence for this hypothesis in the ability of bacteria to survive extreme environments). What is important however is the reinforcing of the idea there is some "missing link" in the history of the transition of chemistry to biology which is definitely not in the fossil record!

The fact we can't discover some intermediary complex molecules between the primeval Earth and the bacteria means for most of the scientists that either Life simply "hitched a ride" on some comet or meteorite to come here from some other place in the Solar system it originated (possibly Mars) which in turn would imply that the entire Solar system gave rise to a single "type" of Life and therefore even if we find Life outside Earth it will probably be based on DNA and the central dogma and be too much like our own or that the emergence of Life was so fast it simply can not be by chance! I think the implications of the second case are greater but the first one can make a lot of "noise", too I guess (especially if they find bacteria on Mars and they turn out to be just like those here). I myself, however, am a little bit of an "heretic" here and believe the continuous occurrence of the same fossils everywhere in the ancient geological record (and in meteorites from Mars, too) may indicate a little bit different view of what Life can be defined as. What we are looking here are not evidence of cells, but rather evidence of metabolic products which we (not they by themselves) contribute to cells! Because modern cells can produce such products we assume they are produced by cells! But we don't have cells we can look at under the microscope in those rocks. We have thin bands of material we think comes from cells (it is the same with the Martian meteorites-science in a way becomes a "point of view" which you should consider isn't very "scientific"). But what if these bands were the result of metabolism, but is was not cellular! I myself think this is entirely possible, but most of my colleagues do not even consider this idea. This can easily explain the rise of products of metabolism early on but at the same time give enough time for the complexity of the modern cells to form under the influence of great competition among metabolic pathways themselves, rather than living cells-for which we seem to have direct evidence at a much later period. This hypothesis can also explain why are all the basic metabolic pathways in Life today so conservative (unlike the genes themselves which determine them-what is really more conservative-the gene or its role?) while the proteins coding for them can be coded under different genomic organization-e.g. different structure of the genome in different domains. The place of the gene can change, even to a certain extent its sequence, but what remains the same is their relationship to each other, e.g. their topology to respect of each other in the general graph of metabolism. Why? What if metabolism was more ancient than cells, but the evidence of this "metabolism evolution" was lost in the age before the cell(because there were no cells, no structures, no anything to leave fossils of the metabolism evolution, excepts its waste products (in a way its "coprolites"). I would like to think this evidence supports such hypothesis but again it is just an opinion.

I hope you like this answer.


Can genes that activate transcription factors also called be called transcription factors? If the sole known function of a gene is to activate a transcription factor, would that gene also be considered a transcription factor, or is there a word for such genes that are further upstream on the transcription activation cascade?

Yes.  For an example, see this list of targets of NF-kB (a transcription factor).  Many other transcription factors are included there.  As for a TF that does nothing except activate another, single TF?  I don't know that those exist - TFs tend to modulate multiple genes.

You need to re-write your question, it is ambiguous and your use of terms is incorrect... Assumption: by "activation" you mean "activation of transcription resulting in the expression of the transcription factor"

1) Transcription factors are proteins

2) Genes are comprised of DNA elements

A transcription factor can be involved in initiating the EXPRESSION of a transcription factor, whereafter that second distinct transcription factor initiates the EXPRESSION of another gene that encodes another transcription factor.

Answer: No, genes do not "activate" transcription factors*

*Unless you are proposing the philosophical question of whether the DNA binding domain itself, which endows the transcription factor with a state of being active duty (i.e. fulfilling its purpose as a transcription factor), and thus that purpose is fulfilled only when the DNA binds the the TF, then a DNA binding domain can indeed "activate" the TF... but I'm pretty sure this isn't what you're asking.


Help identifying a bug which looks like a housefly and mosquito hybrid I'm from Kochi, India (southern part of India). I found this bug inside my house , it was about a centimeter long . But how can such an hybrid be possible. (It was raining before I found it).
1: https://i.stack.imgur.com/Dlyio.jpg

This is a long-legged fly (Condylostylus spp).  Unfortunately your image is not sharp enough to give a specific species.  See this post of another Indian fly that is virtually identical to yours:
https://www.jungledragon.com/image/13762/long-legged_fly_-_condylostylus_spp.html


How do animals decide what to eat and what not? I want to know this in particular about animals that no longer eat what they used to eat. The best example in my opinion are chickens. Chickens are often held to eat all kinds of food we would otherwise throw away. Most of this, they would never find in nature.
Chickens almost eat everything, but there are things they don't. Also, they often have a clear preference for some food.

How can they differentiate this food? Do they use smell? Looks? How can they know smells of food they never had before?

To answer with a question: How do you decide what to eat (if you don't know whether something is edible)?

All animals have evolved taste and smell (and I'm sure even prior to eyesight). The purpose of taste and smell in terms of nutrition is to determine if something is edible. If something tastes bitter or extremely sour, this is mostly a warning sign for toxins or advanced microbial degradation. The same accounts for smell: If you let raw meat foul, the smell is unbearable. Why? Because our brain is telling us not to eat this.

Probably a lot of external and internal factors combined. But the most important would be the smell, eye sight and taste.

Smell can be, I would say 60-70%. When some particles arrive to the smell receptors, htne on the cellular level the receptor gives a "report" to other parts of the bady, especially brain etc. E.g. some seabirds, like storm petrels, recognize the odor of a compound emitted by krill, their main fare.

Almost all birds have great eyes, so this is a great long-distance food check.

But to be honest the taste is also a big issue and I think that all birds go through a phase when they eat everything and after learning what tastes good and bad (with combination of how it look like before they eat it and how it smelled, the infomrmation is stored in the brain.

Even though the birds have problems with complicated thought processes in their brain, I think that they are more than capable of storing and reusing this "good-bad-food" information from their brain.

There could be other factors like e.g. some birds are allergic to some food (yes, animals can be allergic too, even though their immune system is much stronger then ours) and the body will store in the brain to not eat that in the future.


Is post-transcriptional regulation of gene expression an epigenetic process? Is post-transcriptional regulation of gene expression (for example regulation by microRNAs) a type of epigenetic gene expression regulation?

I think we can categorize it as epigenetic since the DNA sequence is not changed, but I have never come across that terming in any papers. Does someone have any idea, or know of any papers that categorize post-transcriptional regulation as epigenetic?

miRNAs and other post-transcriptional regulators are very well "genetic". They are encoded by genetic elements, are expressed and are affected by mutations. Just because this mode of regulation was not well known previously, it should not be classified as an epigenetic mechanism while the traditional protein based transcription factors (TF) are not.

Epigenetics, as it is originally defined (the "formal definition") is about mechanisms that can perpetuate the state of a cell to its next generation. Inheritance of gene expression programmes is therefore epigenetic. Although the gene expression programmes themselves can be implemented via different factors including protein and RNA based regulators, they would not necessarily constitute the epigenetic mechanisms that lead to inheritance of this state.

rg255's point of view is that any mechanism that causes a variation in the functional aspects of the genome without altering the genome sequence itself, would be epigenetic. This is technically correct but in that case all gene expression regulators including TFs should constitute epigenetic mechanisms.

Now, the main issue is where to draw the line between gene regulation and epigenetics?

In my opinion, the epigenetic mechanisms are one of the ways to regulate the gene expression. Although histone modifications and DNA methylation regulate gene expression and also confer heritability to the gene expression programme, the heritability can be implemented without them as well.

You can imagine a cell as a vessel which runs a system of biochemical reactions. This system can have multiple steady states (for e.g. multiple fates of a stem cell). To perpetuate a state, the new cell just needs to have the right initial conditions. This can be proved mathematically too. Such a system can be implemented via the traditional transcription factors as well. So what is epigenetic?

IMHO epigenetic was a loose term to denote something that people were not fully aware of, at that time. Anything that was not directly mediated by transcription factors was termed as epigenetic, including long distance regulators, non-coding RNA etc.

BOTTOMLINE

I would not classify non-coding RNAs as "epigenetic" for the very reason that they are encoded by genes and have more or less a direct effect on the target genes, just like TFs (which are apparently not epigenetic). As for the papers, there were many papers that used to assign these under epigenetic mechanisms, but that is IMO just too vaguely arbitrary. (Ironically, I happened to come across miRNAs and lncRNAs while I was doing a summer project on epigenetics and was reading relevant papers.)

What should be considered epigenetic would be a subject of another debate.

I disagree with rg255 on this. Most if not all of posttranscriptional modification is encoded in the actual DNA sequence. Those microRNAs for example can be determined by reading the DNA bases or finding the encoded enzymes that do RNA editing (like C to U by TPR enzymes). The DNA sequence already encodes all the information that will determine if it will get modified or not.

Epigenetic regulation on the other hand are encoded on the histones and other proteins associated with DNA and can by definition not be understood by reading the sequence (e.g. acetylation and methylation). This information does not code for proteins or transcripts.

EDIT:
A quick Pubmed search underlines what most scientists think is epigenetic Pubmed search. You see loads of methylation/histone research but miRNA or transcription factors are nowhere to be seen.


Is the strength of presynaptic stimulus on the postsynaptic neuron affected more by the dendrites, or the cell body? Is the strength of presynaptic stimulus on the postsynaptic neuron affected more by the properties of the dendrites & axon terminals, or the cell body & axon?

Two years ago I asked a question here and learned that neurons do have a bias, and that various factors affect that bias, and now I'm trying to learn more specifically, how much of the strength of the the strength of a synapse, i.e. the size of the effect of a presynaptic stimulus on the postsynaptic neuron is dependent on the properties of each individual axon terminal / dendrite terminal, vs how much is dependent on the properties of the axon or cell body.

And do the properties of each individual axon terminal / dendrite ending vary diversely, even among dendrites of the same neuron, or do individual dendrites and axon terminals of the same neurons typically have similar properties?

It depends on the type of axon, of course.
In Axosomatic synapses the properties of dendrite is not important, but for Axodendritic synapses, the properties of post syn. dendrite is more important as the amplification and other processing happen there. However, Soma is much nearer to Axon hillock, so changes by Soma wouldn't be declined as the impulses won't. It may be depended on neuron properties itself and so that's wrong to generalise!


Are mitochondrial genes decoded in the same way as nuclear genes? Mammalian mitochondrial genomes contain only 22 tRNA-coding genes, which is an insufficient number to decode mRNAs under the standard wobble rules.

How is translation of mitochondrial mRNAs achieved with this number of tRNAs?

The possibilities that occur to me are that certain genes encode multiple tRNAs (but this appears unlikely as each gene has its own promoter) or that mitochondrial tRNAs can adopt alternative three-dimensional structures, each with a different anticodon loop and hence a different anticodon.

Answer Summary

  Translation in the mitochondria of mammals differs markedly from that
  in the cytoplasm. Although it has more similarity to translation in
  prokaryotes, it also shows significant changes from the latter. A smaller
  repertoire of tRNAs is able to translate a ‘simplified’ genetic code
  through structural alterations and base modifications that allow their anticodons
  to decode groups of synonymous codons, not possible according to the standard wobble ‘rules’.

Relationship to the eubacterial translation system

One of the pieces of evidence for the endosymbiotic theory of the origin of mitochondria was the fact that their translation machinery was more similar to that of prokaryotes than to that in the eukaryotic cytoplasm. The similarities to prokaryotes included the (smaller) size of their ribosomes, the susceptibility of their ribosomes to antibiotics specific for bacterial ribosomes, and the formylation of their initiator tRNA — fmet-tRNA.

Although in no way rebutting the endosymbiotic theory (which is widely accepted), mitochondrial translation shows several differences from that in prokaryotes. These include there being a single tRNA to decode methionine in both initiation and elongation (discussed below), the lack of leader sequences preceding the initiation codon, hence precluding a Shine & Dalgarno type of recognition by the ribosome, and additional ribosomal proteins which are thought to “provide a specialized platform for the synthesis and membrane insertion of the highly hydrophobic protein components of the respiratory chain”.

Decoding with 22 mitochondrial tRNAs

General Review: Suzuki et al. (2011) Annual Review of Genetics 45, 299–329

As the question states, mammalian mitochondria encode 22 mitochondrial tRNAs, which would be insufficient to decode mRNAs using the standard genetic code and the wobble ‘rules’ that apply to translation in the eukaryotic cytoplasm and in prokaryotes.

One way out of the dilemma would be if some of the tRNAs were encoded in the nucleus and imported into the mitochondrion in a similar manner to that of nuclear-encoded mitochondrial proteins. Although this turns out to be true for certain organisms (although the import system is different from that for proteins), and important in some cases, this is not the answer for mammalian mitochondria. Thus, as reviewed in Current Genetics (2009), the mitochondrial tRNAs encoded in the nuclear genome of H.sapiens only duplicate the 22 mitochondrial tRNAs and their anticodons. (The one exception is an extra Gln(anticodon CUG) in addition to the Gln(anticodon UUG).)

Let us look more carefully at the problem. Although there are 61 codons specifying amino acids, because of wobble, fewer than this number of tRNAs are required to decode them. The left-hand frame of the figure below shows the standard genetic code, and the minimum number of tRNAs needed to decode it using the wobble ‘rules’ shown beneath, indicated by the colour-coded rectangles.

For those not familiar with the actual pattern of wobble (summarized in my answer to another question), in elongator tRNAs the 5′-position of the anticodon has some flexibility such that a G in that position can form base pairs with U or C in the 3′-position of the codon, an inosine (I) can pair with U,C or A, but an anticodon C can only pair with a codon G. The unmodified bases A and U are rarely found in anticodons, but a variety of different chemically modified Us are found (U* in the figure) which only pair with A. Thus, the minimum number of elongator tRNAs needed would be the number of coloured rectangles — 36 — and, as there are separate species of tRNAmet for initiation and elongation, the minimum number of tRNA species is 37.

When the human mitochondrial genome was sequenced, two anomalies stood together: the limited number of tRNA genes already mentioned and (more sensationally) changes from the standard genetic code (indicated in red on the right-hand side of the figure). It was immediately realized that these changes served to rationalize the code so that all synonymous codons were in groups of four or two. If it were assumed that the decoding specificity or wobble of mitochondrial tRNAs were different, then 22 tRNAs would be sufficient using the ‘wobble’ shown beneath the right-hand frame of the figure for groups of four amino acids (dark blue) and groups of two amino acids with codons ending in A or G (red).

One further requirement was that a single tRNAmet be involved in both elongation and initiation, a requirement the fulfilment of which has already been mentioned.

What features of the tRNAs could change the wobble ‘rules’ that have been conserved between prokaryotes and eukaryotic cytoplasm? There turn out to be two types of changes. The first, and most obvious, is the fact that certain (but not all) mitochondrial tRNAs have non-canonical cloverleaf structures, the most extreme being tRNAser in which the whole D-loop is missing. The second is the post-transcriptional modification of bases in the anticodon — just as is the case for tRNAs in the cytoplasm, this can markedly affect decoding specificity.

It is not yet possible to describe the codon–anticodon interaction in mitochondrial translation in the way that this has been done in for the cytoplasm or for prokaryotes. The problem would appear to be the difficulty of obtaining sufficient pure tRNAs. Whereas it is easy enough to clone and transcribe the tRNA genes, this is insufficient without the secondary chemical modifications of the bases which is key to the structure and function of the tRNAs.

It turns out (and I’m not a 100% sure of this) that every tRNA-coding gene could give multiple variants of anticodons by different folding ways, so that you’d have enough anticodons in the end.


The selective pressure of contraceptives Is it possible that the use of contraceptives will produce evolution humans? Contraceptives can reduce reproductive success, so shouldn't selection favour resistance to them?

In this case it might be useful to think of evolution as a "black box", an information processing mechanism  where only input and output is relevant. From this point of view, we would expect the box to produce an output comparable to the resistance that evolution will produce in a population experiencing a poisoning effect which seriously damages its reproduction mechanism.

The evolutionary "output" from such poisoning  has been studied in great detail. Are there any lessons relevant to future human evolution in these studies?

Interesting question, but the answer is simpler than you might think.

Antibiotics put selective pressure on bacteria. Bacteria resistant to that antibiotic evolve as only the resistant ones survive. But this is the key, there has to be at least some already resistant bacteria from which the new (resistant) population will emerge.

With contraception, this is not the case. There are no spermatozoids capable of penetrating condoms, for example, and you should also bear in mind that in most cases mild hormonal disbalance is enough to prevent conception. It's a very delicate process, and contraception is basically an overkill.

Even if some spermatozoids could penetrate condoms, that trait would have to be hereditary in order for evolution to occur.

If you'd want to prove that contraception constitutes selective pressure on humans you'd first have to prove that there are spermatozoids and egg cells that can beat contraception, and that it's hereditary.

Evolution doesn't work the way you think it does. If you kill a random person, even if you kill a million people, it's not necessarily selective pressure. There are rules to evolution, and one of them is that it has to be hereditary.

This is not.

It wouldn't even come close to being artificial selection, let alone natural selection.

Besides, there's 7.3 billion of us. More than ever. We can hardly say contraception is reducing the world's population.

You also fail to see one thing, that a person who uses contraception in teenage years still has kids as a young adult. Contraception just delays pregnancy until you're ready. In evolution, there's a concept of "surviving long enough to reproduce". You can both use contraception and be an organism with 10 kids - though not at the same time.

Do you mean that (A) the choice of using contraception is part of the human phenotype and we can study the selection pressures that apply to it or that (B) you consider the absorption of a contraceptive as an external selection pressure and are wondering what evolutionary answer this selection pressure will cause?

If (A):
One can only study the evolutionary pressures applying on the use of contraception under the following conditions:

The choice of using contraceptive is inheritable
People who do use contraceptive have significantly less (or more) kids over their entire life than people who do not

I am not sure any of these conditions is fullfilled.

If (B):
If it was as simple as a "poisoning effect which seriously damages its reproduction mechanism", you could expect the emergence of a resistance allele (for example that would make females insensitive to oestrogens in oral contraceptives).

However I guess that persons who use contraception are likely to choose abortion if pregnant, decreasing the fitness effect of such a potential resistance allele.


In the vacuum of space would death be instantaneous? I was arguing with my colleague about this matter (I'm not going to mention which side I fall on).

Would death be immediate in the vacuum of space? For example, if I was suddenly teleported into the vacuum of space would I die straight away? Or would I experience a suffocating sensation?

Nope, you wouldn't die instantly. While explosive decompression has never been tested on humans (for obvious reasons), the dangers of a vacuum have mostly to do with the pressure differential between your body and the now pressure-less void around you. The most fragile parts of the biological system would be the lungs and ears, and the instantaneous transportation would cause a severe case of the Bends if you were rescued quickly enough. You would pass out within a few seconds stated by NASA when an experiment went awry, and death might be from lack of oxygen to the brain, although after a few minutes everything bad starts to happen so nobody really knows what you would die of:

  At NASA's Manned Spacecraft Center (now renamed Johnson Space Center) we had a test subject accidentally exposed to a near vacuum (less than 1 psi) in an incident involving a leaking space suit in a vacuum chamber back in '65. He remained conscious for about 14 seconds, which is about the time it takes for O2 deprived blood to go from the lungs to the brain. The suit probably did not reach a hard vacuum, and we began repressurizing the chamber within 15 seconds. The subject regained consciousness at around 15,000 feet equivalent altitude. The subject later reported that he could feel and hear the air leaking out, and his last conscious memory was of the water on his tongue beginning to boil.

If an astronaut were teleported into space without her spacesuit/helmet, she would feel a suffocation feeling, likely making breathing motions even though there is no air to breathe.  She would also feel her sweat, saliva, tears, mucous, and any other water on her body boil off, though her body would maintain blood pressure, at least until her heart stopped. She would be unconscious within 15-20 seconds and dead within 90-120 seconds.


What's the worst that can happen from eating too many spicy peppers? Can you die? Some peppers, such as the habanero or Carolina reaper are extremely spicy, and when eaten in larger amounts than one is accustomed to, can cause some discomfort.

I've also heard anecdotes claiming that pepper spray, if applied with sufficient intensity, can cause death.

What if you were to eat as many spicy peppers as possible, despite the noxious taste? Is it possible to commit suicide in this way (and what would the cause of death)? Would you faint from excessive mouth pain? Would uncontrollable vomiting prevent you from consuming further peppers?

The more "dangerous" properties of spicy peppers are chiefly due to capsaicin.
Sigma-Aldrich sells purified capsaicin, for which they provide safety information, including an MSDS. Most of it is the usual, unsurprising set of warnings about irritation to eyes and the respiratory system. However, there are LD50 numbers:

LD50 Oral - rat - male - 161.2 mg/kg
LD50 Oral - rat - female - 148.1 mg/kg
LD50 Dermal - mouse - >512 mg/kg

From this, we can conclude that one would have to eat quite a bit of capsaicin to die. If lethality in humans is exactly the same as rat (which it probably isn't),  a 70 kg human would need to consume about 11 g of capsaicin to reach similar levels of lethality.
The Carolina Reaper, one of the hottest known peppers, averages about 1.6 million on the Scoville scale. Capsaicin amount is related to Scoville heat units, so we can make an imprecise conversion from one to the other.
Using values given in 2 publications (Nwokem 2010 and Al Othman 2011) we can observe the following trend:

So on average, about $6.25 \cdot 10^{-5}$ mg/g capsaicin per SHU. With this, we get $(1.6 \cdot 10^5) \cdot (6.25 \cdot 10^{-5}) = 10$ mg/g, or 1% capsaicin for dry Carolina Reapers. To eat the equivalent of 11 g of capsaicin in peppers, you would have to eat 1.1 kg of dry peppers - which should be a couple of dozen.
So, I think we can conclude that it is relatively "feasible" to consume a dangerously large amount of capsaicin by eating very spicy peppers. However, there are numerous caveats with my reasoning:

Human LD50 and rat LD50 are not necessarily the same.
Toxicity is not necessarily linearly related to body weight.
Peppers have compounds besides capsaicin that contribute to hotness.
It would be very difficult to eat such a large amount of spicy peppers, and various involuntary reflexes would interfere. Even if one were force fed the peppers, I imagine the body would attempt to vomit it up - which brings up the question of how the toxicologists even managed to feed several milligrams of capsaicin to rats to measure the LD50.

If you have cardiovascular problems, then it should be quite possible for the pain cause by spicy peppers to trigger a heart attack via a spike in blood pressure. A similar scenario might occur with respiratory diseases. And of course an anaphylactic shock, if you are allergic.

Apart from such special circumstances, I imagine that it would be nearly impossible to overcome the debilitating effects of capsaicin long enough to consume a lethal dose.


Differential Gene Expression I have a matrix two gene expression datasets, one from 10 normal individuals and ten from diseased individuals, which are normalised log fold change values--, i.e., already processed.

My question is: how do I obtain a list of differentially expressed genes?
That is the up and down expressed genes. I was thinking of getting means for each group and then sorting the average fold change values would work, but I am not sure...

Thanks.

It hard to figure out what sort of data you have. qPCR? Let me give you an example with tools involved on how I get differential genes for RNAseq data, that is whole transcriptom and for mouse that transcriptom that's about 23000 genes.

Step 1. Map raw reads to the reference genome.
Step 2. Count number of reads within the feature. Feature can be several things, but lets just take protein coding feature (feature == gene).
Step 3. Do differential expressions analysis

From step 2 you get a matrix of counts.

      sampleA_rep1 sampleA_rep2 sampleB_rep1 sampleB_rep2
gene1      2             5        20             23
gene2      10            12       50             50
gene3      20            23       4              6
..
geneN

The packages that I use are limma and/or edgeR. You can find them on bioconductor Both packages take raw counts and give you topTable of DEG, default is top 100 genes.

I recommend reading edgeR or limma manuals, there come with great explanations as well as examples. Also A scaling normalization method for differential expression analysis of RNA-seq data is original paper that explains TMM normalisation (mention a bit more in depth below)

Two things; one you need to filter genes with low counts, convert to cpm() counts per million before filtering as this takes library size (depth of sequencing) into consideration. two calcNormFactors() will do TMM

The hardest thing (I understand) in RNAseq is to get total RNA output for each sample. Because a treatment will effect the number of transcripts expressed in that sample, increasing or decreasing amount of transcript, which give you unbalanced counts. You won't know just by looking at raw counts if geneA has less counts because it's been down regulated OR because that sample after treatment has more transcripts present in the cell and geneA simply has less coverage, due to other transcripts also getting reads now. I can't really explain that too technically because I don't understand this myself, but TMM normalisation takes care of this and  gives you an estimate of degree of variability.

I know that I'm not giving that much info on actual differential testing, which was your question. edgeR has exactTest() which is Exact Tests for Differences between Two Groups of Negative-Binomial Counts , which might help you, but you might have normalise your counts differently as mentioned above. The general idea (I understand) is you need to fit a model (lmFit()) and then do the test eBayes()

Other

Degust this is very nice tool that uses limma and edgeR in the backend, but simplifies a lot of things as well as gives you nice interface to work with your data. You upload raw counts! in the format shown above
DESeq one of the other rather popular R packages that can also do differential gene testing

There is software for this, but if you want a very primitive way to analyze it, do a t-test (which is basically looking at both the difference in means and the STDEV of each group)


Can Phosphogycolate buildup in a plant kill it? I'm trying to think of some things for the science fair, for part of my experiment I need to know if Phosphogycolate build up in a plant can kill it. Also, are there any chemicals that may disrupt the enzymes which break down phosphogycolate. Thanks!

Phosphogycolate can break down enzymes needed in the Calvin Cycle along with other enzymes in a plant so that is a yes.l.


Is there anything that is completely non-toxic to humans at any dose? Lately I have seen a number of unrelated "scientific" debates over whether certain substances should be outlawed because they are toxic to humans. My initial, informal reaction is usually to respond that anything is toxic to humans if you give them a sufficiently large dose.

However, formally I don't know if that's really true for everything a human being could ingest in some way. I started to wonder if there were some substances that our body could handle unlimited amounts of without any negative consequences.

As this question has been (correctly) identified as a bit vague, I'll try to explain what i'm looking for. For the purposes of this question, I'm willing to ignore the limitations of actually ingesting a given substance in "the usual way". For example, if you can't physically drink enough of some liquid fast enough to kill you without your stomach filling up and vomiting, but that same liquid injected intravenously could be lethal, I could consider that toxic. I also recognize that the body can only physically contain a certain volume of stuff, after which sheer pressure would cause it to fail; I'm more interested in "biochemical toxicity" as opposed to any physical damage (I just don't know the term for what I'm looking for.)

In other words, one of my goals is to learn if, under laboratory conditions, a properly motivated researcher could always find a dose that would be toxic, regardless of the impracticality of a real person ingesting that dose under normal circumstances.

So, with that qualification, my ultimate question is:

Is there any substance we know of that is completely non-toxic to humans at arbitrarily large doses ingested over an arbitrarily short period of time?

I’ll answer this theoretically, since that’s how it has been posed. And if we’re ignoring practicalities, we may as well posit that the substance in question will be introduced directly into the bloodstream (This is, of course, simple to do in reality, but not how most people consume their non-toxic substances.) The easiest way to show that any unspecified substance can be toxic at an unlimited volume is to invoke the human body’s mechanisms for volume homeostasis.

As mentioned in this answer, the human kidneys functioning optimally can produce up to ~ 25 L/day of urine.1 This would require complete suppression of ADH (anti-diuretic hormone, a.k.a. arginine vasopressin), which would occur only if the “toxin” load were markedly hypotonic (think water).2  There is therefore a theoretical maximum volume of any substance that can be dealt with by the body, which is something less than 25 L per day. (For any substance other than water, the maximum will be lower because ADH will not be as fully suppressed by a less hypotonic load.)

A volume of any substance introduced into the bloodstream (including a product precisely mimicking the constituents of the bloodstream itself!) will overwhelm the body’s homeostatic mechanism. This will result in edema which is unpleasant and, in the case of pulmonary edema, certainly pathologic - a “toxidrome” in your scenario. In the case of hypotonic fluids, serum osmolality will also fall causing hyponatremia with all of its consequences.

Summary: No, the human body can not tolerate an unlimited volume of anything, therefore there is no substance that is non-toxic "at any dose."

1. Christopher Lote. (2012). Principles of Renal Physiology. Springer New York.

2. No, you may not drink 25 liters of water per day. For one thing, urine can not be made with a tonicity of 0 to balance this (more like 60 mOsm/kg minimum). Additionally, ADH can rarely be completely suppressed, yielding a somewhat more concentrated urine and therefore lower tolerance for hypotonic intake before serum osmolality is compromised.

Vitamin C won't kill you no matter how much you get into your body as long as it is enough to help prevent arterial wounds and atherosclerosis(This happens in people with scurvy or vitamin C deficiency because of how cholesterol is used to help repair the wounds and this can lead to a complete blockage of the artery and thus an infarction of all the tissue that artery supplies. So if you don't want to have an MI, one of the things you have to do is get vitamin C into your system.

Another example of this is chloride ions. While having high chloride ions might cause there to be a slower reaction time(since chloride acts as an inhibitor in neurons) it itself won't kill you. Yes it might affect the muscles by not having them contract as much as they are supposed to but this is naturally cured by urinating out more chloride and thus more sodium which can lead to a sodium deficiency which is bad because your body needs sodium in order to function. With a low amount of it it you wouldn't be able to think clearly or even have a normal heart rhythm which might lead to bradycardia from a higher pottasium concentration in the heart.


Why isn't a virus "alive"? The recent news about a new supermassive virus being discovered got me thinking about how we define viruses as non-living organisms whilst they are bigger than bacteria, and much more complex than we first gave them credit for.

What biological differences between viruses and cellular organisms have made viruses be deemed non-living?

If this is a topic that really interests you, I'd suggest searching for papers/reviews/opinions written by Didier Raoult.  Raoult is one of the original discoverers of the massive Mimivirus and his work will lead you to some truly fascinating discussions that I couldn't hope to reproduce here.

The main argument for why viruses aren't living is basically what has been said already.  Viruses are obligate parasites, and while plenty of parasites are indeed living what sets viruses apart is that they always rely on the host for the machinery with which to replicate.  A parasitic worm may need the host to survive, using the host as a source for energy, but the worm produces and synthesizes its own proteins using its own ribosomes and associated complexes.

That's basically what it boils down to.  No ribosomes?  Not living.   One advantage of this definition, for example, is that it is a positive selection (everyone "alive" has got ribosomes) which eliminates things like mitochondria that are sort of near the boundary of other definitions.  There are examples on either side of something that breaks every other rule but not this one.  Another common rule is metabolism and while that suffices for most cases some living parasites have lost metabolic activity, relying on their host for energy.

However (and this is the really interesting part) even the ribosome definition is a bit shaky, especially as viruses have been found encoding things like their own tRNAs.  Here are a few points to think about:

We have ribosome encoding organisms (REOs), so why can't we define viruses as capsid encoding organisms (CEOs)?
Comparing viruses to a living organism such as a human is absurd, given the massive differences in complexity.  A virus, really, is just a vehicle or genetic material, and would be more rightly compared to a sperm cell.  Is a sperm cell alive, or is it a package for genetic material that is capable of life once it has infected/fertilized another cell?
The really large DNA viruses often create cytoplasmic features called virus factories.  These look an awful lot like a nucleus.  What is a nucleus anyway?  Maybe it's just a very successful DNA virus that never left.
Viruses can get viruses.

I'll wind down here, but suffice to say that while our current definition may have sufficed for a while, and still does, it is no longer quite solid.  In particular, there is a theory alluded to above that eukaryotic life itself actually formed because of viruses.  I can expand on this if you like, but here are some great sources:

Boyer, M., Yutin, N., Pagnier, I., et al.  2009.  Giant Marseillevirus highlights the role of amoebae as a melting pot in emergence of chimeric microorganisms.  PNAS.  106(51):21848-21853 (http://dx.doi.org/10.1073/pnas.0911354106)

Claverie, JM.  Viruses take center stage in cellular evolution.  2006.  Genome Biology.  7:110. (http://dx.doi.org/10.1186/gb-2006-7-6-110)

Ogata, H., Ray, J., Toyoda, K., et al.  2011.  Two new subfamilies of DNA mismatch repair proteins (MutS) specifically abundant in the marine environment.  The ISME Journal.  5:1143-1151 (http://dx.doi.org/10.1038/ismej.2010.210)

Raoult, D. and Forterre, P.  2008.  Redefining viruses: lessons from Mimivirus.  Nature Reviews Microbiology. 6:315-319. (http://dx.doi.org/10.1038/nrmicro1858)

Scola, B., Desnues, C., Pagnier, I., et al.  The virophage as a unique parasite of the giant mimivirus.  2008.  Nature.  455:100-104 (http://dx.doi.org/10.1038/nature07218)

Good question; science yet don't know anything about "What is Life".

Yes. Everything about life we discuss (whatever by a Newton, Descartes or Schrodinger), it is in a level of Sci-fi, or hardly alchemy. Anyone of us don't know actually what is it.

The best characteristic of life is, "we, the living-creatures, can sense . We have consciousness" .

But alas, anyone can judge its own consciousness. We can-not judge someone else or any-other object contains any consciousness or not. We can just guess other's consciousness from facial expressions (say cry) , behavior, polygraphs, physiological reactions (respiration, growth, ageing etc... ), complication, informational-content, reproduction, genetic-code and such.
(https://www.youtube.com/watch?v=evQsOFQju08 , Is Your Red The Same as My Red? by Vsauce)

(however a living object can lose consciousness for a while such as when we're chloroformed).

In the same-way, we just guess presence of life in other objects from the complication, chemical structure (carbohydrate, proteins, lipid, DNA etc), metabolic reaction etc. and same evolutionary origin . same to us. In strict-logic we can't tell a lovely flying bird  contains life and is conscious that an alien-robot is nonliving, lacking consciousness. We can guess, not prove, yet.

In the same logic, all virus, viroids and prions (the organisms of "border zone") (including biggest viruses) could be (and often is) compared with living-organisms (like we're), due to their similar chemical structure, genetic codes, information content, reaction etc. with us, as-well plausibly same origin with us.

There exist too, causes to consider all virus, viroids and prions (including biggest ones).  I can call you alive. I can call your one organ (say hand) alive, could call a cell alive. But what we could call 1 protein-molecule? Just like a concrete-mixing machine (known to be nonliving), the protein-molecule is similarly made up of atoms... and nothing else. There is no evidence for "vital-forces" also... the protein molecule operates its works just with electromagnetic forces, thermal-collisions etc. There is no "sign" of life . In the same-way, a virus, viroid or a prion is just a lump of molecule. And for a big virus? a small hut (nonliving) : big house :: small virus : big virus. A big virus would be similar to a big bottle of nucleic acid.

Any more-discussion would be completely opinion-based, but in my-opinion it is better to consider these borderline-organisms as alive, due to more valid-logic such as

They're similar with us in chemical structure, genetic code bla bla bla ...
They are plausibly same in origin with us.
Inert structures, like plant-seeds if contain life, then in same logic we can imagine life in virions etc.
We found different level of parasitism in living organisms, such as  ATP-parasites (I forgot example and can't find right now), and consider them as alive. So why we'll not consider a "protoplasm-parasite" a living-organism?


Is it possible to stop more/extra fat from being stored in the body? I don't mean simply by restricting eating or upping the activities, but a way to basically stop the body from adding more fat on itself down on the bio level. For example, I'm not too knowledgeable on this, but I believe fat is stored when the body can't make any extended use of extra energy put in to it.

Given such, could we simply direct the body to only use the energy needed and dispose of any "extra" while not storing it as fat/triglycerides? I know there are drugs that can speed up metabolism and etc., but this only heightens the body's ability to remove said fat -- not stop the process at which it is stored

This would be a great thing because then we could assure the body only uses the energy on what can be beneficial to us -- all the "rest" can be removed and not stored on us and being a con instead of a pro.

So in summary: Is there any feasible way this could be theoretically possible, given our biochemistry/physiology?

Fat storage comes from conversion of glycogen (a glucose polymer) to triglycerides (fats).  (source: https://en.wikipedia.org/wiki/Glycogen).

Intuitively, the simplest way to prevent fat storage is to block conversion of glycogen to fats. Unfortunately, this will cause a glut of glycogen which can cause an entirely different set of problems (see https://www.hopkinsmedicine.org/health/conditions-and-diseases/glycogen-storage-disease ), so you would want to couple this with a mechanism to eject excess glycogen.

Referencing what user1136 posted: uncoupling oxidation from phosphorylation is a really bad idea. That would basically "burn" fuel while blocking the expected ATP outlet. This will cause a dangerous energy buildup in the mitochondria which has to be unloaded somewhere - provable simply by conservation of energy. Energy can be converted to other forms of energy, but it is never destroyed. Physics is the ultimate anti-cheat tool.

Blocking expected energy outlets is almost always a bad idea in practice. Just to name some practical examples:

In archery class, instructors will warn you never to "dry-fire" a bow (draw the string back and release with no arrow). This can compromise the bow's structural integrity, causing it to splinter, snap, or explode later.
Microwave ovens should never be operated empty with no sink for the electromagnetic radiation they produce - this can damage them. See https://physics.stackexchange.com/questions/309154/what-happens-in-an-empty-microwave-oven for more info.
If you jam the pistons in a standard cylinder-based combustion engine (prevent them from moving), you end up with a lot of energy that needs to go somewhere, which will end up as massive vibration and extra heat - either of which could damage the engine as the design never expected this to happen.


Small worm living in some kind of cocoon, what are these animals? I am curious what animal is this. It is/lives inside some kind of cocoon, about 1 cm in length. They are attached to walls and to the ceiling, but sometimes they fall off. Inside the structure there is a small worm that can come out at both ends alternatingly. It can then hold on to the ground to move the cocoon around. They are said to feed on paper.

This little dude is not a Caddisfly, but a true moth,  Tinea pellionella, a case making clothing moth.  Confusing because they do resemble caddisfly larvae cocoons more so than those of their own family (Tineidae).  Sort blurb Here:

  "The brown-headed larva spins a silken case that is open at both ends. The case in the above image is covered with fine sand and debris, and superficially resembles a caddisfly case. The flattened case is about 10-11 mm long (3/8 to 1/2 inch). When crawling, the larva's head, thorax, and three pairs of legs protrude out of the case, and drag it along. According to Internet sources, the larva feeds on a variety of material, including hair, fur, silk, felt, feathers, woolen clothing, upholstered furniture and carpets. It apparently prefers darkness and soiled clothing, and is not fond of synthetic fabrics, such as nylon and polyesters."

This is a wild stab in the dark, so downvote me as you see fit: Caddis fly larvae (Insect Order Trichoptera). I thought caddis larvae were aquatic though.


Why is the DNA helix anti-parallel? Why is it that DNA strands are running in anti-parallel fashion? Given the chemical base-pairing, they could have been parallel just as well.

Parallel nucleic acid double strand is possible but it is not as stable as the antiparallel form (Szabat and Kierzek, 2017). This is because the nucleobases are not aligned in a way that is conducive for the Watson-Crick (WC) type base pairing. In parallel conformation, the bases can form Hoogsteen (HS) and reverse Watson-Crick (RWC) type base pairing (see below).

You can see that these base pairs are not as strong as that in WC base pairing:

No triple bond between G and C in RWC base pairing
GC pair occurs in HS base pairing only when C is protonated at low pH

Formation of parallel helices, therefore depends on the sequence.

  In general, the formation of duplexes with parallel strand orientation
  is determined mostly by the sequence context and pH conditions.
  Fragments of RNA or DNA capable of forming a parallel duplex are often
  rich in A and C, which is related to their ability to become
  protonated, in middle acidic conditions.

However, it is not as simple as RNA/DNA base pairing with its complement. Parallel helices would not follow the WC base pairing rules and therefore predicting whether they will form is not that straightforward. However, parallel helices can form in vivo (see references 23–25 of Szabat and Kierzek, 2017).

You can also check out this article by Leontis et al. (2002) for hydrogen bond patterns in parallel and antiparallel helices.

This is more chemistry than Biology.

Both strands of DNA are 5' to 3' direction. Why so? because the direction is determined in terms of the direction in which purine or pyrimidine bases are added.

The four bases that exist in DNA are Adenine, Guanine, Thymine and Cytosine. They are referenced under Purine and Pyrimidine links posted above.

This molecule is added to the end of a new DNA molecule.
It will be added to the 3' end of a new growing DNA molecule.

"Adenosintriphosphat protoniert" by NEUROtiker - Own work. Licensed under Public Domain via Commons.

What is the 3' and 5' end?

The ribose sugar at position two will lose the OH, the 5' position is the one where the long chain of phosphates are added in the top image and this phosphate at position 5' will be bonded to the OH at position 3' seen in the deoxyribose molecule, this reaction will generate a phosphodiester bond.

"Phosphodiester Bond Diagram" by File:Enlace fosfodiéster.png, File:PhosphodiesterBondDiagram.png: User:G3pro (talk)
Original uploader was User:G3pro at en.wikipedia.org
Derivative work: User:Merops (talk)
Derivative work: User:Deneapol (talk)
Derivative work: User:KES47 (talk)
Text tweaks: Incnis Mrsi (talk)
Text tweaks: DMacks (talk)) - File:Enlace fosfodiéster.png. Licensed under CC BY-SA 3.0 via Commons.

And here's the complete reaction

If you have noticed the negative charge on the Oxygen, then you will notice that Oxygen has one more electron to donate for a covalent linkage. So this electron attacks the O-H bond at the 3' OH of the deoxy-ribose sugar to generate the phosphodiester bond.

So the 3' OH is always a requirement for addition of new bases to a DNA strand. The 5' refers to the dangling 5' end of the first Phosphate, while the 3' refers to the 3' OH of the Ribose sugar at the last base of the DNA. The entire reaction is catalysed by DNA Polymerase

P.S. They are not really free, there are many modifications which make them inert.

So that is why DNA is anti-parallel.


Engineered CD8 T-cell therapy for HIV infection CD8 T-cells are effective in controlling HIV during the early phase of the infection. However by the time, the virus mutates and develops an evasion mechanism against CD8 T-cells.
Since cancer cells also develop immune evasion mechanisms, and scientists are using several technics to block those mechanism, i think it would also be possible to control "viral escape".
I made some research regarding HIV immunotherapy, however the only thing i found was antibody based immunotherapy.
My question is, would it be technically possible to engnieer custom CD8 T-cells which will targed HIV infected cells ?

People in the comments suggest that this would "Drive the patient into AIDS sooner", or that this will be ineffective because of dormant virus.  Neither is correct.

The question is asking about engineering CD8 with engineered T cell receptors specific for HIV.  This is a logical approach, and multiple groups have tried it:

In Vivo Suppression of HIV by Antigen Specific T Cells Derived from Engineered Hematopoietic Stem Cells
Reconstitution of anti-HIV effector functions of primary human CD8 T lymphocytes by transfer of HIV-specific alphabeta TCR genes
Development of CD8+ T cells expressing two distinct receptors specific for MTB and HIV-1 peptides
T-cell engineering by a chimeric T-cell receptor with antibody-type specificity for the HIV-1 gp120

A brief search on Pubmed will turn up many other articles. Some of these approaches have entered clinical trials; for example:

Redirected High Affinity Gag‐Specific Autologous T Cells for HIV Gene Therapy

The problem with this approach is not that it will "drive the patient into AIDS sooner".  A strong CD8 T cell response controls HIV well, and although it might be one contributor to CD4 T cell loss it's no longer believed that it's a major cause, especially in the early stages of HIV infection.

The general problem with CD8 control of HIV is that the virus is capable of mutation to avoid control by CD8s. Essentially, every case of HIV is effectively controlled by the CD8 T cell response in the early stage of infection, but the virus then mutates and escapes control, then the CD8 response adapts and controls the virus once again, and the virus mutates and escapes ... This can and has been tracked in many patients, showing repeated rebounds of the virus in the blood correlated with CD8 changes.

Better CD8 control of HIV is linked to a broader CD8 response -- that is, attacking many viral proteins, so that viral escape requires multiple simultaneous mutations (exponentially more difficult for the virus).  (Alternatively, the CD8 response can attack a small number of proteins that are very constrained, so that the virus can't successfully mutate them.  However, for reasons related to MHC restriction, that seems to only work in a small minority of people.)

An engineered CD8 T cell response will inevitably be to one or a small number of viral proteins.  That's conceptually similar to the natural situation following HIV infection, meaning that the outcome could be the same -- viral mutation and immune escape.

Because engineering the TcR means you can pick your targets rationally, you might be able to do better than the natural situation, but it's not obvious.  Overall, the fact that groups have been working on this approach for decades, without a breakthrough cure yet, suggests that it might be useful but isn't going to be a slam-dunk.


How many people are required to maintain genetic diversity? Imagine humans were to colonize a distant planet and it was a single one-way trip. How many people would they need to bring?

Obviously 2 is the minimum, but that would result in a lot of inbreeding.

So what number is the minimum number of people you can have in an isolated community and still maintain a healthy diversity?

Actually it is a very important question for laboratory animals (and, I imagine, endangered species) and was calculated to be 25 couples.

With any number of animals (including humans), there is always some inbreeding happening, but you can reduce it with the number of breeding pairs and careful pairing. When you get to 25 pairs (50 animals) and have complete control over pairing, you can sustain the genetic diversity practically infinitely (especially if you take into account spontaneous mutations).

Of course, such control over who can have children with who (plus whether one is at all allowed to procreate and what will be the sex of their children!) would be questionable morally, so in case of populating a distant planet, we would need a larger group, to provide for sexual preferences, fertility problems etc.

Some information on laboratory outbred stocks.

You only need a single female. The space ship could carry a database of genetic material in the form of frozen sperm and eggs. The first female would impregnate herself to breed and raise as many daughters as she can, using as much genetic variety as possible. The daughters would do the same once they can.


Is a single polynucleotide necessarily and always a nucleic acid? I am confused. I know that a DNA molecule is made of two polynucleotides.

But does each polynucleotide represent one nucleic acid? If so, a DNA molecule is made of two nucleic acids, right?

Or do the two polynucleotides (that form a molecule of DNA) make up only one nucleic acid? If so, a DNA molecule is only made of one nucleic acid, right?

There are two types of nucleic acids: 1) DNA --> which is double-stranded, so it's made of only two polynucleotides 2) RNA --> which is single-stranded so it's made of only one polynucleotide. So if we get back to my original question "Is a single polynucleotide necessarily and always a nucleic acid?" --> the answer is no, for DNA is a nucleic acid and it is made of two polynucleotides.


Why a cell contains all DNA when it only needs a few genes? Is that what they called junk? Why does a simple cell have the DNA code for everything else when it just needs a few codes to function? Wouldn't that be a wasteful?

Why does a cell contain all DNA when it only needs a few genes ?

I interpret this question to mean "why does every cell contain the whole human genome even though it doesn't use it all, i.e. why does a liver cell contain the genes for eye color?"

If that is what you meant, then we can easily answer the first question in your actual text:

  Is that what they called junk?

No, that is not what is called "junk DNA". "Junk DNA" can refer to many concepts, but generally it refers to parts of DNA that serve no function in the body: they are not transcribed into proteins, they don't serve to regulate other genes, and if you remove them or change their sequence this will have no effect on the overall organism. This means it refers to parts of DNA that are used nowhere in the body, not parts that are used in one place but not in others.

How much DNA is "junk", how useless it actually is, and why we have it are complex questions that don't all have known answers, but it is completely different from your headline question.

I don't have the time to look up a detailed answer to your first question so I will leave that to others, but here are some elements that might help:

1) I think cells use more genes than you realize. I don't know the proportion of genes that are used for the cell to live as a cell vs those that are used for the specific tasks this cell needs to do beyond maintaining itself and reproducing, but I'm pretty certain there is no cell in the body that "only needs a few genes". I would even guess all cells in the body use most of the genes they contain.

2) not all cells contain an unmodified copy of the whole genome. Some cells lose their nucleus, i.e. their DNA entirely (red blood cells); others multiply some genes that they use a lot.

3) having said all that, I would guess that liver cells indeed don't need the genes for eye color, yet they might have them. Consider that cells reproduce by copying themselves, and copying their whole genome. Is it more of a waste to keep the copy as it is, or to go around before or after the copying cutting out all the bits this specific cell won't use? Do I go around editing the code of my text editor and recompiling it to get rid of all the functionalities I don't use? I might save some space on my hard drive but it is very obviously not worth my time to do that either. If the extra DNA doesn't do enough harm, there is no reason it would be taken out; indeed the wasteful thing would be to do so.

Whether there is junk DNA

The common view of a gene is a sequence of DNA which, upon transcription, which I assume in your understanding is a process by which DNA is read by a RNA polymerase to produce mRNA, and upon translation, produces a functional protein to regulate cellular metabolism (sum of all chemical reactions in a cell). It is not until the discipline of epigenetics emerged that we discover that most of other non-protein-coding sequences have important regulatory functions on the protein-coding sequences. Without them, the cell simply has no clue as to when it should produce more of a protein and when it should produce less, or whether the protein should be produced at all. And of course, DNA also encodes information about rRNA, which is an integral component of ribosome, which you know, is imperative for protein synthesis. Thus, the ‘functions’ of the DNA cannot be limited to protein synthesis, and after extension of the concept of functions, the parts of DNA we can dispense with are incredibly small.

Then let it be argued that those small parts of DNA which really serve no functions are the junk DNA. In fact, even this view is untenable because the ‘functionless’ DNA may be situated between the important sequences that can subtly affect the chemical properties of the protein interactions during an important biochemical process. Specifically, consider NtrC, a bacterial transcription regulator that activates transcription by directly contacting the RNA polymerase. Note that the regulatory sequence (the part of DNA the protein binds to) is very distant from the promoter of the gene(the part of the gene that RNA polymerase binds to). To directly contact it, DNA looping must occur. It is a phenomenon in which an otherwise linear DNA macromolecule is looped out(imagine bending a wire so that two extreme end of the wire touches each other) to allow for the contacts between molecules. Since the protein has such biochemical properties that allow it to contact another protein at a distance, we do not know what will happen if the ‘junk DNA’ the DNA spacing the promoter and the regulatory sequence is deleted. It is well possible that the two proteins will not make contacts anymore. And DNA looping is also ubiquitously found in transcription regulation of eukaryotes.

Why a cell needs to contain all the DNA when it only needs a few genes to function

Once the notion of junk DNA is found to be elusive. This question’s premises no longer hold. But let’s assume there are really genes that when deleted have no observable effects on the phenotypes of the cells or their health, why does not nature delete them during differentiation of stem cells? To explain it in evolutionary terms, there are two main mechanisms nature can design to keep the ‘functionless’ genes at bay during differentiation of stem cells. One is to silence them by wrapping them in a compacted nucleosomal structure, or to delete them once and for all. We do not know if nature has once experimented with deletion, if it has then this design must have endowed less fitness then the wrapping model. What reasons then can we speculate about the failure of the deletion model? To delete the useless sequences, there is a widespread effects on the length of the DNA, the resultant secondary structure (topology of the chromatin). And a protein must be designed to specifically recognise what genes to delete, together with the cooperation of nucleases. This is analogous to writing a computer code that contains information that specifies some of the codes to be deleted while not influencing the instructions of the code that follow, all while being consistent in the process. This is logically possible, and we can never say this design is entirely prohibited. But computationally this is not as elegant a solution than just genes in the DNA that code for a repressor protein for the ‘useless’ code when the right time has come, or by just using proteins to wrap around the sequences to render them unreadable.

Whether ‘non-functional ‘ DNA constitutes a waste

Not at all.