Replication, Transcription and Translation

[LuisP]

This is a extensive post. If you don’t have at least 10 minutes to read and another 5 to think … then maybe best you stop here.

That said,
If already familiar with basics about DNA/RNA, scroll down to (c) The “Central Dogma” of molecular biology.

That’s where it gets juicy.

If not, best read on ... and grind it.

All modern life on Earth (let’s leave at that for now, I’ll get to it in the end) uses three different types of biological molecules that, each, serve critical functions in the cell. (i) Proteins are the workhorse of the cell and carry out diverse catalytic and structural roles, while the nucleic acids,(ii) DNA and (iii) RNA, carry the genetic information that can be inherited from one generation to the next.

RNA, which stands for ribonucleic acid, is a polymeric molecule made up of one or more nucleotides. A strand of RNA can be thought of as a chain with a nucleotide at each chain link. A nucleotide is made up of a base (adenine, cytosine, guanine, and uracil, typically abbreviated as A, C, G and U), a ribose sugar, and a phosphate.

But that’s not important in this context, just science tags on minutiae.

(a) Differences between DNA and RNA :
1 - The main difference is that the ribose sugar backbone in RNA has a hydroxyl (-OH) group that DNA does not.
2 – A major difference is that DNA is usually found in a double-stranded form in cells, while RNA is typically found in a single-stranded form. This lack of a paired strand allows RNA to fold into complex, three-dimensional structures.
RNA folding is typically mediated by the same type of base-base interactions that are found in DNA, with the difference being that bonds are formed within a single strand in the case of RNA, rather than between two strands, in the case of DNA.
3 – Another and minor difference, is that DNA uses the base thymine (T) in place of uracil (U).

(b) The role of RNA :
Despite great structural similarities, DNA and RNA play very different roles from one another in modern cells.
RNA plays a central role in the pathway from DNA to proteins, known as the "Central Dogma" of molecular biology. An organism's genetic information is encoded as a linear sequence of bases in the cell's DNA. During the process known as transcription, a RNA copy of a segment of DNA, or messenger RNA (mRNA), is made. This strand of RNA can then be read by a ribosome to form a protein.
RNAs also play important roles in protein synthesis, as well as in gene regulation.

(c) The “Central Dogma” of molecular biology :
Simply put, this is an explanation of the flow of genetic information within a biological system, or a bit more exactly, with the “detailed residue-by-residue transfer of sequential information”.

It states that “such (sequential) information cannot be transferred back from protein to either protein or nucleic acid”. It is then a one-way circuit. Again, to put it simply, it can be described as a process whereby "DNA makes RNA makes protein".

This dogma (not to be confused with the linguist meaning of this word) is then a framework for understanding the transfer of sequence information between sequential information-carrying biopolymers, generally meaning, inside living organisms.

There are 3 major classes of such biopolymers: DNA and RNA (both nucleic acids), and protein.
There are 3×3 = 9 conceivable direct transfers of information that can occur between these. The dogma classes these into 3 groups of 3:
- 3 general transfers (believed to occur normally in most cells),
- 3 special transfers (known to occur, but only under specific conditions in case of some viruses or in a laboratory), and
- 3 unknown transfers (believed never to occur).

The “general transfers” describe the normal flow of biological information: DNA can be copied to DNA (replication), DNA information can be copied into mRNA (transcription), and proteins can be synthesized using the information in mRNA as a template (translation).

This is the normal process.

However,
this Central Dogma does not preclude the reverse flow of information from RNA to DNA, but only the reverse flow from protein to RNA or DNA.
Remember, to put it simply, it can be described as a process whereby "DNA makes RNA makes protein" and now also where “RNA makes DNA but where protein cannot make DNA”.

Meaning, the Monster inhabits the flow of relations between the “DNA/RNA” dynamic duet, so to speak. (relations … funny word, “relations” is. What does it mean ?).

Because a “Reverse Transcription” can occasionally occur (yet to be explained by science), meaning, the normal “circuit” gets inverted (yet to be explained by science) and “information” then flows from RNA … back into DNA.

And what happens, when this “Special Transfer” happens ?
Alien things happen …

For it then gives birth to Retroviruses, such as HIV. Or it generates Retrotransposons, which can induce mutations. Or it allows for Telomere Synthesis, meaning, a telomere-shortening mechanism that limits cells to a fixed number of divisions and is responsible for aging on the cellular level and sets a limit on any lifespan.

See what I mean ?
No ?
Well, no surprise there. No one sees. Some, among the best of us, “suspect”. And that is all there is.

Now take what follows, hope you can keep pace and trot along,

(d) Eukaryotes, or Modern Life on Earth
The defining membrane-bound structure that sets Eukaryotic cells are set apart from other cells (generally called Prokaryotes) by a specific membrane-bound structure called “the nucleus”, or nuclear envelope, within which the genetic material is carried.

For those into semantics, the name comes from the Greek ευ (eu, "well") and κάρυον (karyon, "nut" or "kernel"). I could summarize it in plain English as “wellness cells”, and no improper innuendo in it ! )

Cell division in eukaryotes is different from that in organisms without a nucleus (Prokaryote). There are two types of division processes :

- In mitosis, one cell divides to produce two genetically identical cells, with no sexual “intercourse” being required. Cancer cells do it, for instance.
- In meiosis, which is required in sexual reproduction, one diploid cell (having two instances of each chromosome, one from each parent) undergoes recombination of each pair of parental chromosomes, and then two stages of cell division, resulting in four haploid cells (gametes).
Each gamete, in turn, has just one complement of chromosomes, each a unique mix of the corresponding pair of parental chromosomes.

Of the 3 “domains of Life”, Eukaryota appears to be monophyletic, meaning, “descendants of one (hypothetical) common ancestor” even if “assuming that it would be one individual or mating pair, is unrealistic, for sexually reproducing species are “by definition” interbreeding populations.

Regardless, it is but one of the three domains of life. The two other domains, Bacteria and Achaean, are prokaryotes and have none of the above features.

Thing is (another one !) Eukaryotes represent a tiny minority of all living things !

However … however,
Eukaryotes first developed approximately 1.6–2.1 billion years ago. And if sexual reproduction is widespread among present day eukaryotes, evidence suggests that only facultative sex was present in the common ancestor of all eukaryotes.

That is … it was not required, back then. Only “optional”, so to speak (ahem).

Do eukaryotes feel “pleasure”, I ask ? Or do they “induce” it ? How come a non-essential prerogative became a “widespread” one ? More,

More, what about if one knows that many extant protists (for the illiterate like me, a type of microorganisms) usually reproduce asexually under favorable conditions, but tend to reproduce sexually … only under “stressful conditions”, such as
- nutritional limitation and heat shock.
- oxidative stress, that is, oxygen excess

Is that not, say, strange ? Is our present "environment" then not the best "favorable conditions" for Life ... before ? Who are these protists, and what are they telling us ?

So, before that “characteristic” oxygen of our atmosphere was present in abundance, they didn’t need sex to reproduce ! And btw, reactive oxygen leads to DNA “damage”. Which “damage”, one may ask ? Telomerase-synthesis, for instance ? Sure, precisely.

Fascinating stuff … !

(e) Food for Thought
We now know that 80% of the human genome is transcribed even though only 1% codes for proteins. What happens to “the rest” ? Is it “stored” ? is it “used” on “backups” through RNA ? Yet to be understood.
We already know that RNA is just a single-stranded form that lacks a paired strand (like DNA), and that this allows RNA to fold into complex, three-dimensional structures.
We also already know that RNA plays a central role in the pathway from DNA to proteins. Central, and nowadays, in “modern Earth life”, the “normal” path.

But now comes the gut-wrenching punch,
The central role for many proteins in a cell is to catalyze (accelerate) chemical reactions that are essential for the cell's survival. These proteins are known as enzymes.

Until relatively recently, it was thought that proteins were the only biological molecules capable of catalysis (that is, able to enable the rate increase of a chemical reaction), but in the early 1980s, however, research groups found that RNAs can also act as catalysts for chemical reactions !

This class of catalytic RNAs are known as ribozymes, and the finding earned Altman and Cech the 1989 Nobel Prize in Chemistry.

And what do these ancient, billion year old ancestral “ribozymes” do ?

They cut a single longer strand of RNA into …. two smaller segments ! Meaning, we now have a “paired strand form” originating … not from DNA, but from RNA only !! Asexual reproduction, so to speak, of the Life Code.
Millennia before DNA.

And why is this important ?

Well, because the discovery of ribozymes supported a hypothesis, known as the “RNA World Hypothesis”, that earlier forms of life on Earth (Pre-Modern Life) may have relied solely on RNA to store genetic information, to catalyze chemical reactions and to pass along “the code”.

Meaning, this suggests that the use of RNA by early lifeforms to carry out chemical reactions …. preceded the – complete - use of proteins !

According to this Theory, Life later evolved to use DNA and proteins due to RNA's “relative instability and poorer catalytic properties”, and gradually, "ribozymes became increasingly phased out."

Sure …
For behold !, in that process we got rewarded …. with Sex, which became "widespread". Which is great (ahem), were it not for its Price !
Because that “phase out” of RNA and the “supremacy” of DNA brought along with it not only sex … but also Retroviruses, Retrotransposons and Telomere Synthesis, which is to say, AIDS, gene Mutations and Limited Life Spans.

Now,
Was all of this, random ? “nature” played dice until a “correct ultimate formula” was reached ? Like, say, can a monkey pressing keyboard keys for Eternity be able to duplicate Tolstoy’s “War and Peace” ?

Really ?

Enter instead Peter Gariaev. Look up my “Wave Genetics” topic, and think again.

Credits
Myself, for being this loony
http://exploringorigins.org/rna.html
http://exploringorigins.org/ribozymes.html
http://en.wikipedia.org/wiki/Central_do ... ar_biology
http://en.wikipedia.org/wiki/Retrotransposon
http://en.wikipedia.org/wiki/Telomere
http://en.wikipedia.org/wiki/Eukaryote
http://en.wikipedia.org/wiki/Monophyly
http://en.wikipedia.org/wiki/Protist

[Mikado14]

Thought you might like to know Luis. You are causing quite a stir. Your thread here has had hits from the UK, fruitbat and wags who I never would have imagined would come here. Linda keeps coming here to read and is obsessed with certain threads but she apparently has copied this thread link to her site for there are quite a bit of entries from a link at the token.

I find it curious. Someone who was banned because of what you posted, they certainly can't stop reading what you post. Hypocrites all. They wouldn't discuss what you wrote to your face but choose to hide behind Linda and talk up a storm. But then, I could be wrong for I don't go there to read but by the number of entries from links at the Token, well, someone is certainly copying and pasting and to me, that is interest in what you have to say, even if they don't agree for even bad publicity is still publicity and that leads to the question....if they didn't like what you wrote...oh yeah, the hypocrite thing.

Keep up the good posts.

Mikado

[LuisP]

Oh well, don’t take it as too meaningful. I have already talked about some of this inside Kim’s thread viewtopic.php?f=37&t=1083&start=30#p32093 so I will excuse myself from repeating it here, except to say that I am not a “composite” person nor do I front run a “team” or whatever it is that nowadays fancies some guys imagination about my humble self.

From a certain distorted point of view, I should, I guess, be proud of such insinuations made by others about my single labours around these posts. As it is, I only laugh at it, pat my dog and light a Camel.

As everyone knows, there in the latitudes I started - but that no one, there, seems to believe, I may add - I am a family guy who works in a bank that “awoke” to certain worries a few months ago.

So thanks, Mikado, for your support. I will indeed keep on trying to post stuff along my line of thought and worries. May it keep on meeting your approval, and others interest.

Most meaningfully, and to the point of what I tried to convey above on the opening post, I really think it could help if I clarify it some more :

1 - This “Central Dogma” concept was made in 1970 by Francis Harry Compton Crick, OM, FRS (8 June 1916 – 28 July 2004) who, besides being a molecular biologist, biophysicist, and neuroscientist, was most noted – imagine that ! - for being, no more no less, the co-discoverer of the structure of the DNA molecule itself in 1953 !
2 - Besides that insignificant feat, he also has the ridicule credential of being a winner (co-winner, more exactly) of the 1962 Nobel prize for Physiology or Medicine "for discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".
3 - Now, this guy was a scientist, not a semantics scholar. And therefore coined the concept with the term “Dogma” and this was, and is - most eloquently by those who are always more adept at crying Horror than at discovering it – what the Torquemadas on duty noticed. Not the concept, and much less its meanings.
4 - Even if the Man himself explained abundantly that “I just didn't know what dogma meant. And I could just as well have called it the 'Central Hypothesis,' or — you know. Which is what I meant to say. Dogma was just a catch phrase ... I had already used the obvious word “hypothesis” in the sequence hypothesis, and in addition I wanted to suggest that this new assumption was more central and more powerful. ... As it turned out, the use of the word dogma caused almost more trouble than it was worth”.
5 – Fortunately, people that matter do not listen to those Torquemada wannabes. Scientific journals of the first category like Nature and world affairs like “The Economist”, top rate Universities like MIT and Princeton, and several other countless scientific publications like the “Molecular Biology Review” or the “DNA Learning Center” ... think otherwise. And discuss, analyze and probe it deeper. Who knows what they’ll find. I, for one, am looking.

All this to say that, yes, in some quarters what is valued – by some - is never what is ... worthy. Just what “can make a storm”. It is known since Antiquity. They called it “Panem et Circenses”. There has never been a shortage of clowns since then and bread is still a cheap commodity, so no big deal, really, when I see it.

That said,
I must finish with the fact that I did appreciate the company of most of that crew, most notably Hobbit, who taught me a lot and whom I respect deeply to the point of not only missing him and his unique perspectives and knowledge, but also his friendly orientation and advice. A good man. And that says it all.

But life moves on.

Below follows some links (there are countless available) if you are interested in deepening the “Central Dogma Concept”.

Nature magazine paper
http://profiles.nlm.nih.gov/ps/access/SCBCCH.pdf
MIT
http://ocw.mit.edu/courses/chemical-eng ... 2007_w.pdf
Princeton Univeristy
http://www.princeton.edu/~achaney/tmve/ ... ology.html
Molecular Biology Review
http://www.ncbi.nlm.nih.gov/Class/MLACo ... dogma.html
DNA Learning Center
http://www.dnalc.org/resources/3d/central-dogma.html
The Economist
http://www.economist.com/node/9333471

[LuisP]

Food for very deep thoughts :

The distinction between prokaryotes and eukaryotes is considered to be the most important distinction among groups of organisms.

Prokaryotes were the only form of life on Earth for millions of years until the more complicated Eukaryotic cells came into being through the “process of evolution”.

Prokaryotic Cell

Or so Science explains it, because to me, this so called “process of evolution” is the biggest Veil ever thrown around our eyes. When you don’t know how something happened and even less how to explain it … it “evolved”.

Right. Sure.

But continuing,
Also, prokaryotes have just 1 chromosome (which is not even a “proper” chromosome, just a Plasmid). Eukaryotes, always have more than 1.

Man, the Supreme Eukaryotic Organism, has 46 chromosomes.

Also - check this ! - Eukaryotes are responsible for every one, every one of the present day Animals and Plants !

Eukaryotic Cell (of a plant)

But prokaryotes endure still.

They are everywhere, actually. For they are the Bacteria and its cousin, the Archaea (meaning, Ancient, Archaic), a form of ancestral bacteria so “alien” that some can thrive in 113 C (235 F) environments, others so acid-tolerant that grow at around pH 0 and others still that are even totally anaerobic, meaning, not requiring any Oxygen to live.

Since these - go figure – have nothing to have “evolved” from, well, Science just “states” they exist and does not even try to explain their existence.

If religions have them, Dogmas, and are ridiculed by some and “unbelieved” in by many because of it, Science - go figure - is not devoid of them. You believe, then, what you believe. For everything requires a “belief” in something.

That is why the more Science discovers, the more evident it is what you should believe in. But whatever ...

Continuing,
We, the Supreme Eukaryotics, could not sustain life without the lowly Prokaryotic bacteria. For billions upon billions of Bacteria live inside Us and use our bodies as their home and sustenance, regulating our “processes” and “functions” in general, a work without which we simply could not “live”.

Also, just imagine !, we would not have Wine and Cheese (just to select these two, to me, very dear examples from thousands available) if Bacteria did not exist.

Thing is, they are also some of the Perfect Assassins. We, the mighty Eukaryotes, have fell – and continue to fall - by the millions at the hands of this last remain of the Prokaryotes, the Bacteria. For some of the worst diseases known to Man are of their make.

And there’s nothing we have come up with till today that will defeat some of them.

Most notorious of all, the terrifying “Methicillin-Resistant Staphylococcus Aureus” (MRSA).

A microscopic, so to speak, Hand of Death.

MRSA around blood cells

Science has thrown everything it knows at it.

To no avail.

And this “Aureus” is not alone. According to a report released by the CDC in September 2013, more than 2 million Americans get drug-resistant infections each year. And about 23,000 die from these diseases that are increasingly resistant to the strongest antibiotics that doctors use to fight the infections.

Yes, prokaryotes and eukaryotes are partners in Life.

But when they fight, yes, the guy that No One Can Explain From Where It Evolved keeps winning.



Yes, you go figure.
And if you find an answer, please tell me.



Credits :
Myself, for being an Unbeliever
http://www.diffen.com/difference/Eukary ... yotic_Cell
http://www.britannica.com/EBchecked/topic/32547/archaea
http://atlanta.cbslocal.com/2014/04/22/ ... -us-homes/

[re-rose]

earlier:

(relations … funny word, “relations” is. What does it mean ?).

"Aho, all my relations" is the prayer we give as we enter the inipi for a sweat ceremony. It means much much more than flesh and blood and genetic connections to me.

rose

[StarCat]

MRSA is the tip of the iceberg unfortunately. We also hhave VRE, c-diff, strep-B and a newer one whose name escapes me right now. University Hospital had an outbreak of it last year. And of course we have the viruses. Noro virus, hepatitis A, B, and C, influenza in its various incarnations, herpes in its various incarnations. And that doesn't even cover the major players.

And then there's this damn sinus infection that I'm still trying to get rid of. Aarghh!

Cat

[LuisP]

Well Cat, my “tip of the iceberg” is this :

1- Eukaryotic organisms
(a) are relatively recent Earthling cells, having “evolved” from other, ancient ones which predates them by millennia.
(b) a tiny minority of all living things,
(c) which, paradoxically, are responsible for every one of the Animals and Plants inhabiting Planet Earth.

Since this is a perfectly reasonable thing to happen, no need to explain it, I guess.

Further,
2 - Eukaryotic organisms have two primary cell types - germ and somatic.
Mutations can occur in either cell type.

If a gene is altered in a germ cell, the mutation is termed a Germinal mutation. And it will be passed on to the next generation when the individual successfully mates, meaning, has sex and procreates.

On the other hand, regarding mutations in Somatic cells, one strange, extremely strange thing, happens :
- Those mutations will not be passed on to the mutated individual’s children. Why ? Because man’s sperm and women’s eggs are Germ cells, and will not be touched by it.

Another perfectly reasonable thing to have happened, and therefore exempt from required explanation.
It simply is, because it is.

Further,
3 - Germ cells are unique to sperm and eggs. All other cells are Somatic. First ones only have 23 chromosomes, are destined exclusively to procreation and to “mate” itselves with another so as to get the other 23 required to form a “Life” cell with 46 chromosomes.

All the other Trillion upon Trillion of cells in our bodies (some estimates say 200 million trillion) are Somatic. They divide by themselves and always with those 46 C’s.

Perfectly reasonable too, this is. Since it ... just is, like this.

Thing is,
A cancer cell is a Somatic cell. And … it passes its mutations to its “progeny”, each divided cell carrying the original mutation of its predecessor one. Not only that, but they, contrary to other somatic cells, replicate exactly and therefore never “age” or “die”.

A unique case, amongst ALL somatic cells.

Now, that’s unreasonable.
Very.

Because we should just die.
Even if Life doesn’t.

Perfectly reasonable, that is, isn’t it ?
That’s why it is unexplained, I guess.