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Mitonuclear match.

Started by Kai, October 17, 2011, 05:42:26 PM

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Kai

This is perhaps the most deceptively simple and important biological insight of this decade. As Huxley said of natural selection, "How extremely stupid not to have thought of that!"

http://blogs.discovermagazine.com/notrocketscience/2011/10/17/the-two-genome-waltz-how-the-threat-of-mismatched-partners-shapes-complex-life

QuoteVirtually all complex cells – better known as  eukaryotes – have at least two separate genomes. The main one sits in the central nucleus. There's also a smaller one in tiny bean-shaped structures called mitochondria,  little batteries that provide the cell with energy. Both sets of genes must work together.  Neither functions properly without the other.

Mitochondria came from a free-living bacterium that was engulfed by a larger cell a few billion years ago. The two eventually became one. Their fateful partnership revolutionised life on this planet, giving it a surge of power that allowed it to become complex and big (see here for the full story). But the alliance between mitochondria and their host cells is a delicate one.

Both genomes evolve in very different ways. Mitochondrial genes are only passed down from mother to child, whereas the nuclear genome is a fusion of both mum's and dad's genes. This means that mitochondria genes evolve much faster than nuclear ones – around 10 to 30 times faster in animals and up to a hundred thousand times faster in some fungi. These dance partners are naturally drawn to different rhythms.

This is a big and underappreciated problem because the nuclear and mitochondrial genomes cannot afford to clash. In a new paper, Nick Lane, a biochemist at University College London, argues that some of the most fundamental aspects of eukaryotic life are driven by the need to keep these two genomes dancing in time. The pressure to maintain this "mitonuclear match" influences why species stay separate, why we typically have two sexes, how many offspring we produce, and how we age.

The original essay is here: http://onlinelibrary.wiley.com/doi/10.1002/bies.201100051/abstract;jsessionid=38BD914A6F8A6CC1CEDA0BB17A6F51BF.d02t04

The mitochondrial-nuclear relationship is one of the oldest and most important aspects of eukaryote biology. The mitochondria, at one time free living bacteria, are internal obligate symbiotes of the eukaryotic cell. Not only that, but their bacterial genome is parsed down from thousands to thirteen; the rest of the management genes have been transferred to the nucleus, but are still necessary to make the electron transport chain work well and not leak free radicals all over the place. Therefore, there is heavy selection for the nuclear and mitochondrial genomes to be compatible, since free radicals (electrons without a nucleus) are high energy and dangerous to life. They cut through tissues, mutate DNA and generally wreck havock. When a mitochondria stops working correctly, it either kills it's host cell (general cell death), or turns off the self kill ability (cancers). This and telomere length on nuclear chromosomes are probably what causes aging, as the telomeres shorten, allowing more copy errors, and mutations and copy errors accrue in the mitochondrial genome. And this accelerates as the electron leak worsens, in a feedback cycle. Which would explain the quick degeneration rate of people with end life diseases. And since this relationship is directly related to longevity, fecundity, and gene compatibility, it's no wonder that evolution has selected very widely used reproductive aspect of two sexes (with mitos passed down by only one), because multiple lineages of mitochondria in a single cell would decrease the total compatibility. It also explains why organisms with high energy lifestyles, like bats and birds, have low fecundity, because only embryos with highly compatible mitonuclear matches would survive development; the leak threshold is lower, the efficiency necessarily higher. Conversely, rats have lower energy efficiency needs, so they have higher fecundity. This also brings up another point, that species with lower leak levels have longer lives; pigeons, for example, live much longer than rats.

These are all, I think, majorly important ideas and routes for research, especially when it comes to aging and life extension.
If there is magic on this planet, it is contained in water. --Loren Eisley, The Immense Journey

Her Royal Majesty's Chief of Insect Genitalia Dissection
Grand Visser of the Six Legged Class
Chanticleer of the Holometabola Clade Church, Diptera Parish

Freeky

Interesting brain chew, Kai.  Thanks. :)

Don Coyote


Cramulus

This is all really interesting - I didn't realize that the mitochondrial DNA evolve faster.. and I'm not sure I entirely understand why.

I would have guessed nuclear DNA evolves faster because it has more variance?

What does it mean that "nuclear and mitochondrial genomes cannot afford to clash"? in what ways do they clash?

Don Coyote

Quote from: Cramulus on October 17, 2011, 09:43:29 PM
This is all really interesting - I didn't realize that the mitochondrial DNA evolve faster.. and I'm not sure I entirely understand why.

I would have guessed nuclear DNA evolves faster because it has more variance?

What does it mean that "nuclear and mitochondrial genomes cannot afford to clash"? in what ways do they clash?

To add to that, wouldn't sharing and mixing genetic material from two(or more) parents increase the likely-hood of new variations showing up, or does that restrict it by preventing genetic material that is too variant from creating a viable cell?

Do mitochondria reproduce within cells during the cell's lifespan?

Cramulus

Quote from: Cramulus on October 17, 2011, 09:43:29 PM
This is all really interesting - I didn't realize that the mitochondrial DNA evolve faster.. and I'm not sure I entirely understand why.

I think I figured it out. Mitochondria reproduce multiple times during an organisms life, whereas nuclear DNA only makes it out of the barn during reproduction.

GOT IT NOW!

Kai

That's right, Cram, but remember it's only the mitochondria in the germ tissue that gets passed to the mother's offspring. So not a massive amount of times, but still more than nuclear DNA.
If there is magic on this planet, it is contained in water. --Loren Eisley, The Immense Journey

Her Royal Majesty's Chief of Insect Genitalia Dissection
Grand Visser of the Six Legged Class
Chanticleer of the Holometabola Clade Church, Diptera Parish

Cramulus

In what ways can they clash with the nuclear DNA?

Kai

#8
Quote from: Donald Coyote on October 17, 2011, 09:56:34 PM
Quote from: Cramulus on October 17, 2011, 09:43:29 PM
This is all really interesting - I didn't realize that the mitochondrial DNA evolve faster.. and I'm not sure I entirely understand why.

I would have guessed nuclear DNA evolves faster because it has more variance?

What does it mean that "nuclear and mitochondrial genomes cannot afford to clash"? in what ways do they clash?

To add to that, wouldn't sharing and mixing genetic material from two(or more) parents increase the likely-hood of new variations showing up, or does that restrict it by preventing genetic material that is too variant from creating a viable cell?

Do mitochondria reproduce within cells during the cell's lifespan?

To answer your questions:

1. Nuclear and mitochondrial genes cannot afford to clash because this leads to mitochondrial innefficiency, which leads to leaky electrons, which leads to cell damage and mutation. The electron transport chain within the cristae walls of a mitochondrion is a finely tuned process. If you are familiar with cellular respiration, you'll know that organism that do not use oxygen in the synthesis of ATP (the molecule used to convey energy in cellular processes in just about every organism) have to do so by anoxic fermentation, and they get very little ATP from this process. This is in comparison to aerobic respiration, which from every glucose molecule not only generates two ATP from the anerobic glycolysis, but also 10 molecules of NADH+, which can generate ATP through the electron transport chain. This is nearly a 10-fold increase in efficiency.
The way the electron transport chain works  is the electron from the NADH+ is passed intermembraineously through a series of protein gated channels that direct hydrogen ions out of the inner area of the mitochondrion. For every one NADH+, three hydrogen ions are directed out. (Note: after the electron is done passing it's energy off to the gated channels, it is donated to an oxygen (which causes a water molecule to be created), just to keep a free electron from making trouble). Now, this causes a hydrogen osmotic gradient; there are now more hydrogen molecules outside the inner area than within. This hydrogen gradient moving downslope through the cristae walls back into the inner area of the mitochondrion is what drives the major production of ATP from ADP.

Interestingly, mitochondria have not retained all the genes to make this process work. They have some of the genes in the Electron Transport Chain, and all of the necessary bacterial tRNA genes, but none of the enzymes that run the citric acid cycle. Most of the necessary components have been, at some time in evolutionary history, donated to the nucleus of the cell; they are no longer stored in the mitochondrial genome. Therefore, to make aerobic respiration work, many of the components must be donated by the nuclear genome. You can see how important it is that these do not clash, then, as any component that lowers the efficiency will result in A) some lost energetic potential and B) a leaky electron transport chain which allows free radicals to escape. The components can clash in the sense that they are proteins, and proteins are folded structures of ammino acids, and if the folded structures do not fit together precisely, they do not work correctly on what ever purpose they are designed.

2. The hypothesis of mixing mitochondrial material being more inefficient, is because any one line of mitochondria isn't guaranteed to be a good match with every nuclear genome. Having only one mitochondrial lineage matched with one genome means that, if there is not a good match, that individual will not survive to maturity and will not reproduce, therefore that pairing will not continue in the population. If there are multiple lineages, then perhaps only one of those will be a good match, thus lowering the overall efficiency. Having only one mitochondrial lineage means that, if the pairing works, there aren't going to be problems of inefficiency from other involved pairings. Another reason could be that of aniosgamy, that is, that the gametes (egg and sperm generally) are significantly different in size. The sperm's mitochondria often doesn't even make it into the egg, and when they do, they are significantly outnumbered (1 million to several hundred) by the mitochondria of the egg, and are in a degraded state from the transfer.

3. Mitochondria do reproduce within cells over a lifetime; obviously copy errors in nuclear and mitochondrial DNA decrease respiratory efficiency over a lifetime. And while they reproduce generally at the same time as nuclear reproduction, they reproduce separately, the same way bacteria do, by fission. However, only the mitochondria in the germ layer tissue is passed to the offspring, and these generally reproduce only a small number of times compared to the rest of the tissues in an organism.

I should note, the other reason why mitochondrial DNA mutates faster is because it IS closer to the electron transport chain, and even in a high efficiency operation there will be some occasional leakage. mtDNA also doesn't have as robust repair mechanisms as nuclear DNA. The mitochondria can't even replicate or transcribe itself, because the genome doesn't retain a gene for DNApolymerase or DNAtranscriptase.

It's important to remember that when something works in biology, it tends to be conserved. Genetic diversity is all well and good if necessary to deal with a changing environment, but oxidative respiration was perfected a long time ago, and the cellular environment hasn't changed very much since then. Selection on pairings now is due to inefficiency that interferes with fecundity. Since diversity would just lower the efficiency in most cases, these things tend to be conserved. If it works, don't fix it (or break it, for that matter).
If there is magic on this planet, it is contained in water. --Loren Eisley, The Immense Journey

Her Royal Majesty's Chief of Insect Genitalia Dissection
Grand Visser of the Six Legged Class
Chanticleer of the Holometabola Clade Church, Diptera Parish

Kai

It's also interesting to think about how eukaryotic phototrophs (e.g. plants, algae) have to work well with not only mitochondria but also chloroplasts. And sometimes the chloroplasts have come to the lineage through secondary (organism 'eating' an alga that 'ate' a cyanobacteria) or even /tertiary endosymbiosis (organism 'eating' an alga that 'ate' an alga that 'ate' a cyanobacteria).
If there is magic on this planet, it is contained in water. --Loren Eisley, The Immense Journey

Her Royal Majesty's Chief of Insect Genitalia Dissection
Grand Visser of the Six Legged Class
Chanticleer of the Holometabola Clade Church, Diptera Parish

Kurt Christ

So, I was taking a break from studying biochem to read PD.com- and ended up reading Kai summarizing what I was supposed to be studying anyway. Although not a suitable substitute, I found it a rather entertaining happenstance.
Formerly known as the Space Pope (then I was excommunicated), Father Kurt Christ (I was deemed unfit to raise children, spiritual or otherwise), and Vartox (the speedo was starting to chafe)

LMNO

Quote from: 'Kai' ZLB, M.S. on October 18, 2011, 05:50:43 PM
It's also interesting to think about how eukaryotic phototrophs (e.g. plants, algae) have to work well with not only mitochondria but also chloroplasts. And sometimes the chloroplasts have come to the lineage through secondary (organism 'eating' an alga that 'ate' a cyanobacteria) or even /tertiary endosymbiosis (organism 'eating' an alga that 'ate' an alga that 'ate' a cyanobacteria).

That's amazing.  It's so complex, it must have been designed by some higher power!







:asshat:

Kai

Quote from: LMNO, PhD (life continues) on October 18, 2011, 05:56:59 PM
Quote from: 'Kai' ZLB, M.S. on October 18, 2011, 05:50:43 PM
It's also interesting to think about how eukaryotic phototrophs (e.g. plants, algae) have to work well with not only mitochondria but also chloroplasts. And sometimes the chloroplasts have come to the lineage through secondary (organism 'eating' an alga that 'ate' a cyanobacteria) or even /tertiary endosymbiosis (organism 'eating' an alga that 'ate' an alga that 'ate' a cyanobacteria).

That's amazing.  It's so complex, it must have been designed by some higher power!







:asshat:

Hah. Actually, the way we know that secondary and tertiary endosymbiosis has happened is from the remnants of the earlier organisms: in the form of earlier cell walls and membranes, photosynthetic pigments, and DNA. We can trace the lineages back through those leftovers from a not-quite perfect endosymbiosis. This is especially clear in the glaucophytes, a type of Archaeplastida algae (algae being a sort of catch all term for non-vascular photosynthetic organisms, comprising everything from cyanobacteria to diatoms to dinoflagellates to the semivascular charawort; it is not a real or natural group of organisms, it is polyphyletic, but it is a sometimes useful term) which has something across between chloroplasts and cyanobacteria. These cyanelles, as they are called, are more or less cyanobacteria in a state of partial endosymbiosis with the glaucophyte host organisms.  Together with the Rhotophyta and the Viridiplantae (green algae plus land plants) they make up the Archeoplastida, which seem to all have gained their chloroplasts from a single endosymbiosis of a cyanobacteria over 1.5 bya. Though, there is some dispute whether this group is monophyletic or not. I tend to believe it is.

On a side note, I find the way the Eukarya tree is shaping out into 6 or 7 superkingdoms to be very interesting. These are:

  • Archaeplastida: As above.
  • Excavata: A group of unicellular flagellates, many of which have a excavation where the food cavity lies (classic example being Euglena
  • Amoebozoa: A group of mostly unicellular organisms characterized by lobelike, cytoplasmic flow. Classic examples are Amoeba and dog vomit slime mold
  • Rhizaria: A group of amoeboid unicellular organisms with filament or rod like pseudopods. There aren't really any classic laboratory examples of these; the Forameniferans are my favorite.
  • Opisthokonta: Multicellular and unicellular organisms that when flagellate posess a single posterior flagellum. Includes the metazoans (all multicellular animals), fungi, and related groups.
  • Chromalveolata: One or two groups, depending on who you ask, the Alveolates and the Stramenopiles or Heterokonts. The alveolates include cilliates (like Paramecium, dinoflagellates (like red tide), and Apicomplexa (like Plasmodium. The stramenopiles are several groups characterized by two, differently shaped, forward facing flagellae (a familiar but strange member of that group is diatoms). As stated above, these two are together or separate depending on who you ask.
If there is magic on this planet, it is contained in water. --Loren Eisley, The Immense Journey

Her Royal Majesty's Chief of Insect Genitalia Dissection
Grand Visser of the Six Legged Class
Chanticleer of the Holometabola Clade Church, Diptera Parish

Kai

Quote from: Kurt Christ on October 18, 2011, 05:52:04 PM
So, I was taking a break from studying biochem to read PD.com- and ended up reading Kai summarizing what I was supposed to be studying anyway. Although not a suitable substitute, I found it a rather entertaining happenstance.

Don't just trust everything I say, though. Same goes for your textbook, too. I've probably botched part of it.
If there is magic on this planet, it is contained in water. --Loren Eisley, The Immense Journey

Her Royal Majesty's Chief of Insect Genitalia Dissection
Grand Visser of the Six Legged Class
Chanticleer of the Holometabola Clade Church, Diptera Parish

LMNO

Dear Kai:

You are very kind not to end your last post with a "pwned" macro. However, you probably should have.