The Origin of the Nucleus

I just read a fascinating "hypothesis" in the latest issue of Nature entitled Introns and the origin of nucleus cytosol compartmentalization.

The greatest divide in the living world exists between prokaryotes and eukaryotes (yes I know, there are viruses ... but lets not get off topic!).

Generally, prokaryotes are devoid of membrane-bound organelles (including the nucleus, mitochondria, the endoplasmic reticulum), and their cytoskeletal systems are quite simple. These critters' genes do not have introns (aka junk DNA) and their genome does not undergo much recombination. If prokaryotes had a strategy, it would be "multiply faster than your neighbors". We call these critters bacteria and divide them into two groups: archeabacteria (includes many extreme bacteria) and eubacteria (common bacteria).

Eukaryotes on the other hand are complicated machines. They have many organelles that are each specialized to perfom a subset of the cellular functions. In addition most eukaryotes share the same extensive cytoskeletal toolkit. Eukaryotic genes have introns, which must be spliced out before transcribed RNA can be translated into protein. And yes, the genomes of eukaryotic cells swap genes (aka sexual recombination).

Eukaryotes are the result of an ancestral archaebacterium that swallowed up a eubacterium (see pic step #1). The "archaea" gave rise to the nuclear genome the eubacterium gave rise to mitochondria. If eukaryotes had a moto it would be "you don't have to out-race the competition, when you can eat them".
In the article, William Martin from the University of Dusseldorf and Eugene V. Koonin from the NIH propose that the nucleus evolved to physically segregate the production and processing of RNA from the act of translating the RNA into proteins.

So why was this necessary?

They contend that the mitochondrial ancestor must have carried parasitic genes that can copy and paste themselves within the mitochondrion genome. Similar genes, or disarticulate group II introns, have been found in some modern eubacteria. Fortunately these parasites when in their RNA form, can splice themselves out of any RNA transcripts. (RNA + catalytic power = Ribozymes!) OK lets get back to the story ... after being swallowed, mitos replicated and some inevitably died (step#2). The genomes of the dead mitos were then absorbed into the what was the archeabacterial genome (step#3). But now comes the crunch ... mito based parasitic DNA could spread into the archea based genome. Sometimes the junk would mutate and lose the ability to self-splice, however these could still be spliced out by other functional parasitic junk. Apparently there is data that functional group II introns can splice out other introns that have lost the ability to self-splice. These catalytic RNAs became essential and gave rise to the eukaryotic splicing machinery ... aka the snRNAs. The last problem faced was that RNA splicing is much slower than RNA translation. To prevent translation from occurring on unspliced RNAs, the two machineries were segregated into separate compartments: RNA processing in the nucleus and RNA translation in the extra-nuclear, or cytoplasmic, space (step#4).

But there's more!

In eukaryotes, sheets derived from the endoplasmic reticulum (ER) form the bilayered nuclear membrane. Entry and exit from the nucleus is controlled by nuclear pores. According to the authors (although I'll have to check this out) the major components of the ER are derived from archeabacterial genes. This would indicate that the ER was already present in our archaea-anscestor before it swallowed mitos. If we look at nuclear pore components, or nuclear specific proteins, some are derived from archeabacteria genes and some from eubacteria ... thus the nucleus was pieced together using genes from both the host and mito genome ... (drum roll) ... and thus the nucleus arose AFTER mitos arrived.

Great story! Let's see if it holds up.

Ref: William Martin and Eugene V. Koonin, Introns and the origin of nucleusâcytosol compartmentalization. Nature (2006) 440:41-45

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Cool story. One of your neighbors, Jack Szostak, gives a really cool talk about compartmentalizaton in the context of the orgin of life. I especially enjoyed the discussion on whether (if?) the inadvertant or spontaneous compartments drive complexity in the transition from ribozyme/riboswitch soup to organism or whether they (compartments) were actively built from very simple micelles by the RNA machinery which then allowed each organism to evolve.

>eukaryotes had a moto it would be "you don't have to out-race the competition,
>when you can eat them"

Now, that's the intelligent way to design a complex cell ;)

By Gerardo Camilo (not verified) on 03 Mar 2006 #permalink

The prok and euk motos remind me of this great but dense book by John Maynard Smith - The Origins of Life : From the Birth of Life to the Origin of Language.

Basic idea DNA = information

For prokes, DNA = informtion for swamping the competion with copies of yourself

For euks, DNA = complex information (due to sex and gene selection) for destroying the competition

By Acme Scientist (not verified) on 03 Mar 2006 #permalink

...propose that the nucleus evolved to physically segregate the production and processing of RNA from the act of translating the RNA into introns.

Slight correction here. I think you meant "proteins", not introns in that last part.

Bacteria can use their flagella either for fleeing from or holding onto and poisoning and eating euks.

By Pete Dunkelberg (not verified) on 03 Mar 2006 #permalink

Excellent summary of an idea about a question that has been bothering me for a long time. I'm certainly glad that you didn't mislabel it a 'theory'!

One (very common, unfortunately) error that I note yet again: I understand the necessity of being concise, but I must must rail against use of such teleological phrases as ...the nucleus evolved to physically segregate...

We biologists all understand that evolution does not occur TO DO anything; it occurs BECAUSE of something. Saying TO DO implies that evolution is a conscious process in which the DNA gets (or the organisms get) together to decide (INTELLIGENT) how to change to improve the phenotype (DESIGN). Since sloppy shorthand phraseology like this is so common, it's not surprising that non-biologists misunderstand evolution and why ID gets such traction.

Evolution is a response to selection acting on variation (among other mechanisms). It's much less misleading to say: the nucleus evolved because bearers of the trait (and its incipient stages) had an advantage over those which didn't, because it physically segregated..." It's certanly less concise, but also more PREcise.

To all readers, especially those who write for lay audiences: PUHLEEEZ don't ever say "evolved to" when discoursing about evolution. Spend the extra few words to be correct.


Thanks I missed that - I'll change it.

This language is used often among biologists to imply an advantage (in contrast a design), and it's tedious to restate the mechanisms implied in "evolution" with every mention of the term. However I agree, the wording is important - and I'll try to be more precise in the future.

I've made the same mistake, and been slapped down for it.

I understand the need for shorthand ways of expressing terms. Hence the immense bank of scientific jargon, something for which scientists have earned a reputation for being incomprehensible to non-scientists. We must understand that non-scientists use some of the same words differently than we do.

My suggestion is that we stop referring to evolution as a "process" (a word which also has teleological implications) and instead refer to it as a "consequence".

One suggested phraseology: "the trait evolved as a consequence of its ..."

p.s. i think that it is a great presentation otherwise.

Nice post, but I cringed just a little when I read,

Eukaryotes on the other hand are complicated machines.

Let the quotemining begin!

"Bacteria can use their flagella either for fleeing from or holding onto and poisoning and eating euks."

Well the whole "eat" buisness is not absolute - and I must add that usually euks eat other euks.

By Acme Scientist (not verified) on 04 Mar 2006 #permalink

"Well the whole "eat" business is not absolute - and I must add that usually euks eat other euks.

Yes I would say that this is closer to what I meant. And although some (or many) bacteria may feed on eukaryotes, the largest part of the bacterial strategy involves out-multiplying your fellow bacteria.

Eukaryotes have given up this "speed" strategy altogether and instead rely mostly on "advanced technology". And it's all due to sexual recombination.

By promoting gene exchange, sex increases an organism's evolvability. In other words eukaryotes have the ability to change faster than bacteria (by natural selection). Additionally sex increases the number of genes that an organism can have in a stable genome. So although some bacteria have nifty tools, eukaryotes have many more tools per genome. (Although if you compared the tools used throughout the prokaryotic kingdom, it probably dwarfs the total developments found in the entire eukaryotic kingdom).

I must say that certain eukaryotes, such as yeast, have gone back to the strategy of multiplying as fast as possible. Think of yeast as a "back to the earth" movement of the eukaryotic kingdom. They have fewer genes, smaller genomes, and they revert to sexual reproduction only when they run out of food.

Alex, I'm glad you put "hypothesis" in quotes as I can envision no way to test or falsify this nuclear evolution narrative.

By the way, introns aren't junk. Transcription editing is how the human genome codes for 90,000 proteins with only 25,000 coding genes.

Prokayotes have organelles too. There's even one known (God only knows how many there actually are as we've only examined a miniscule fraction of all prokaryote species) membrane-bound organelle, the magnetosome. Not to mention unbound organelles such as ribosomes and flagella.

There's even one known (God only knows how many there actually are as we've only examined a miniscule fraction of all prokaryote species) membrane-bound organelle, the magnetosome.

Yes I stand corrected yet again! I should really change that. It's funny I was thinking of writing something up on the paper in Science that found that magnetosomes are aligned by the MreB homologue. I believe that this is the first example of how the bacterial cytoskeleton ligns up organelles.

As for the introns as junk - just my attempt to dumb it down. The importance of introns is highly controversial. Yes there is alternative splicing, and this is aided by some intronic sequences ... but whether introns have to be so damn long is another story. (I'm actualy studying this question ... hope you can read my paper in a couple of months ...)

Could it be the other way around? Meaning could it be that proks are "devolved" from euks? For example could some proks be ancestors of the mitochondrial remains of some (ancient) euk?

Is there any data that would demonstrate that bacteria to bacteria endosymbiosis is possible? I know we have euks engulfing bacteria and forming a symbiotic relationship. But we also know that euks are complicated machines compared to proks.

Interesting idea. I guess you would call it the mito that got away model. Sadly the weight of evidence goes against this idea.

Mitos are missing too many genes. Most of the important ?mito? genes are actually found in the nucleus and the gene products (i.e. proteins) are reimported into the mito. There are explanations of how mitos lost genes, and why certain genes stayed in mitos and others got absorbed into the nuclear genome, but no feasible explanation (yet) of how or why the reverse process would occur.

Mito genomes are highly relateded across many organisms, and this diversity represents a sliver of the diversity found in the prokaryotic world. If prokaryotes all derived from one mito, you would expect that mitos would be more diverse. It?s the founder effect.

So my answer again is - too much evidence points the other way (gene lineage, fossils of microbes). And the term "devolved" does not make any sense. It would be like saying "deshaved".

In anycase if you want to make advances in this topic, read up on all the data (examples: what are genes in mitos, what genes are in eubacteria, when did eubacteria and eukaryotes appear in the fossil record, how they date fossils ...) and submit an article to a peer-reviewed journal where you propose a feasible model. Your proposal should not only explain all (or most) observations (i.e. data, see above) but makes some testable predictions.

As for falsification, read this excellent article by Mike the Mad Biologist. Likelihood statistics is the goal not falsification.…

As to debating this idea - just keep the comments limited to the scope of the post.

can u pl tell me: if i can see the transcript of a particualr gene ( RT-PCR)but there is no transcription (Western blot)at all what one could conclude? and how to verify this result.

but there is no transcription (Western blot)

You mean translation (I think). Also, from your question, I gather that the message has an open reading frame. Furthermore I'm guessing that antibodies were generated against the encoded protein, or aginst a peptide of the putative protein (for the western).

Well I guess there are three possible answers. 1) At steady state, your protein is at very low levels (below your detection limit). This could be caused (for example) by rapid protein turnover. You can try loading more lysate. 2) Translation of your mRNA is inhibited. Many genes are regulated at the level of translation, perhaps this is the case for your gene of interest. 3) Somethng is wrong with your western blot. Did you load a possitive control to check whether your antibody can recognize protein on a western? You can generate protein in bacteria or in a mammalian cell line (like 293T) and load the positive control in a separate lane.

If your positive control is detectable, and if you can quantify the amount of your protein, this may indicate that your test sample does not have much protein. If the low level of endogenous protein is due to transcription inhibition and you can document how that happens (maybe find the RNA element???) that would be a cool story.

Characterizing introns as junk is probably pretty accurate, in a relative sense, since alternative splicing came after introns. Bacteria and yeast both have some introns, but at low levels, and they're almost always consitutively spliced. On the other hand, eukaryotes probably evolved complicated splicing machinery to deal with mutations in splice sites, and then this in turn allowed for alternative splicing.

By UndergradChemist (not verified) on 10 Jan 2007 #permalink