Wednesday, March 12, 2014

#5 of 5 short stories on the Origin of Life - To Catch a Predator


"We are made of Star-stuff"
The Origin of Life is filled with mysteries. As Neil DeGrasse Tyson says on his reboot of Cosmos "We are made of Star-stuff". Pretty cool, but how did that Star-stuff turn into the life we see today? Well, life today can be split along the cellular/acellular divide, with the smallest self-replicating bacterial cells on one side and viruses on the other. Even the recent excavation of a large 34,000 year old virus hasn't challenged this divide.

But there remains a cellular mystery, which is that all life on this planet relies on one of three basic cell architectures: the Bacterial cell, the Archaea cell and the Eukaryotic cell. But one of these things is not like the others. The Eukaryotic cell is weird. It's really, very, VERY strange. It's an energy-guzzling behemoth that somehow broke the rules of surface-to-volume efficiency and bioenergetics to become a success story on planet Earth. In this post, I'll discuss how the Eukaryotic cell came to be -- it's not about the delightful invention of the nucleus, or about benevolently engulfing a bacterium. It's about the pre-cellular network of life, and a predatory bacterium that invaded that network.

-->If you want the short version you can just watch the movie below, or get the full story by reading below.

Life, Getting Started
Before life could get going a couple pieces had to fall into place. There had to be a complex biochemical ecosystem, that included self-replicating macromolecules. There are now several lab examples of how this can occur such as RNA molecules that self-replicate. Recent efforts have shown that self-replicating macromolecules don't break the laws of thermodynamics, but they do bend them a little. It seems there are rules to how and when self-replication can occur, and self-replicating RNAs are just one example of this. In addition, all life today uses the same chemical language, in the form of ribosomes, that gave form to the chaos of that biochemical ecosystem on the early earth.

An origin for viruses
At this early point, isolated cells would only contain a fraction of this diversity and would have been a hindrance to evolution. Instead, there may have been a Woesian  pre-cellular network of life that connects nodes for processing information -- such as translating ribosomes -- with self-replicating RNAs that jump from node to node, exchanging information through horizontal gene transfer (HGT). Packing up some fraction of this ecosystem would lead to several possibilities. First, let's consider: (1) packages with no self-replicating elements.  These would have little to no impact, as they would transfer material but no information. (2) packages that contain self-replicating elements, let's call this kind of element a virus. Viruses carry information and can carry that information across great distances. This would spread information and bridge physical gaps in a pre-cellular network. If a viral package lands at a processing node, than the information can be amplified and spread further. It is worth noting that today, viruses are still prolific, outnumbering cells on our planet 100:1, so they may well pre-date cellular life as a mechanism of information exchange. Finally, we can consider possibility (3), a package that contains replicating elements (memory) and translating elements (language) would be very special, and have the potential for self-contained replication of the entire package, let's call this a cell.

A Special Package
An origin for bacteria cells
So these special packages, these simple cells, depart from the complexity of the network and start passing their information vertically, from parent to offspring instead of horizontally through the complicated HGT mechanisms of the network. This kind of event may have happened several times, but two lineages of the simplest cellular package survive today - the Bacteria and Archaea. These cells are small, but they are independent.  They evolve. They fill niche after niche across the planet, they learn to use sunlight for energy, learn to breath Oxygen and some of them even learn to hunt. When they hunt other bacteria we call them predatory, when they hunt us humans we call them pathogens. These early hunters became specialists at invading the membranes of other living things, stealing their nutrients before moving on to hunt again.

The Predator that crashed the network
Invasion of the host network
So imagine then, that one of these predatory bacteria tries to invade the pre-cellular network, the network that gave it life. And what if the network didn't want to die? Perhaps the network was invaded and plundered many times, but one time the predator was caught and a balance was struck. First nutrients and then information flow back and forth between predator and the host network. As the predator grows and divides it provides more and more energy to the network, let's call this hypothetical element a mitochondrion. The network provides stability, safety and utilizes the energy from the mitochondrion to build structures of greater and greater complexity. Eventually, something like the events that gave rise to the bacteria and archaea cell plans, gives rise to one additional cell plan. This cell plan is bigger, more complex, but still a self-replicating package. This scenario is one possible explanation for how the seeming impossible Eukarya lineage is born.



The Network that caught the predator
An origin for eukaryotic cells
So, why couldn't a eukaryotic cell arise first and then later engulf a bacterium? (1) Genomic evidence indicates that all eukaryotic organisms descend from a progenitor that had mitochondria. (2) The closest bacterial relative to the mitochondrion is Rickettsia, an obligate intracellular pathogen, that can not live on it's own, but must live inside of a host. So, the mitochondrion likely started with a bacterium invading, rather than a large eukaryotic cell engulfing. (3) Energy. This is the most critical issue. The idea that Eukaryotic cells swallowed a bacterium and then domesticated it is a bit like saying that the first American colonists started building houses with wires and light bulbs because they figured an American would discover electricity some day. Of course, the power source had to be available first. And the mitochondria are the power source of the Eukaryotic cell. So it's worth spending some time thinking about the energetics of the Eukarya cell plan.

Consider this: a typical eukaryotic cell needs 1,000 times more energy to replicate than a bacterial or archaeal cell. Specifically, it takes harvesting enough energy to yield 10 trillion ATP for a Yeast cell to make a brand new copy of itself, compared to a mere 10 billion ATP for an E. coli cell to do the same trick. This means that whenever resources are scarce, let's say only enough energy is available to make 9 trillion ATP in the cell, then the Yeast cell doesn't have enough energy to go from 1 cell to 2 cells, while the smaller bacterial (or archaeal) cell type not only goes from 1 cell to 2 cells, it has enough energy to make as many as 900 new cells. This energetic barrier is also (part of) what prevents bacterial and archaeal cell types from growing as large as Eukaryotes, the larger they get, the more inefficient the cells are at utilizing resources and the less they can reproduce.
    
The Origin of Life
An origin for life based on the Woesian tree
Is this origin story correct? It's hard to say with complete certainty what events exactly transpired across the vast expanse of time that led to life today. But we do have the ability to construct testable hypotheses, which have already led to the resounding proof that all life today descends from the same common ancestor, and that the Eukaryotic cell plan had mitochondria from the beginning. The energetics of the Eukaryotic cell, and the intimate symbiosis with mitochondria both imply that this special symbiosis may have developed before the first Eukaryotic cell left the pre-cellular network.

The Fate of the Network
And what became of this pre-cellular network? Was it permanently crashed by the predator that became the mitochondrion? Was it gobbled up later by all the large, multi-cellular organisms of the Eukarya lineage? Or is it still thriving in some nook or cranny of the Earth today? I'm not sure....what do you think?

3 comments:

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  2. This article makes sense but how would viruses be the key to informational exchange early in time when viruses can't survive without a host? What acted as their host since they do not contain enough genome to survive on their own?

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  3. The network hypothesis is completely new to me, but I really like what it implies. When you consider Pelagibacter ubique, which possesses the smallest known genome of any free-living organism at 1.3Mbp, as our baseline in terms of the "bare minimum" of information a cell needs make all of the gene products necessary for metabolism, replication, homeostasis, ect., the idea that if you took a bunch of organic molecules and throw them into a primordial soup and they just happen to arrange themselves into a cell that can perform the aforementioned tasks is just absurd. Maybe I could buy into it if this was an infinite universe with an infinite number of Earths, but all current evidence suggests that the universe is not infinite (albeit still pretty darn big). After all if the universe IS infinite, that means that somewhere out there is a planet identical to Earth, with the same life forms, and an exact clone of me sitting at his computer and commenting on his genetics professor's blog. And somewhere else is a monkey writing Shakespeare. Infinity is a big number.

    But since this is the only Earth we know of, we have to deal with what's in front of us. And anyone who has any knowledge of intricate regulatory mechanisms that even the simplest cellular life employs, would be hard pressed to say that a ~1Mbp nucleotide sequence came together inside a lipid bilayer in the precise order to allow for synthesis of all of the necessary gene products for it to be considered a cell isn't a bit far-fetched.

    But what I like about this network hypothesis is that not all of these processes (DNA replication, translation, ATP synthesis) had to arise simultaneously within a lipid bilayer. They could have arisen sequentially and carried out in an acellular environment long before the first cells compartmentalized a part of the network and became free living. In that sense, I like it much more than the "primordial soup" hypothesis.

    But there are a couple of things that I question about the network. As we all know, the biochemical reactions that take place inside of a cell are sensitive to temperature and pH (among other things), and therefore require a stable environment and mechanisms for maintaining it. Even the limited chemical activity that occurs within virus is contained by a protein capsule (and sometimes a lipid bilayer stolen from its host). So firstly, if the network was NOT contained (open to the environment), how was it able to accomplish the reactions that are prerequisite to cell formation? Secondly, if the network WAS contained within, say, a lipid mono/bilayer or a protein capsule, then then formation of the network seems just as unlikely as the formation of a cell from primordial soup.

    Still, the network hypothesis definitely has promise in my humble opinion. If it's already been shown that some nucleic acids can self replicate, and formation of amino acids and monosaccharides have been observed to form spontaneously from their organic constituents, then given the right conditions and millions and millions of years, some crazy stuff might pop up.

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