The Nature of Science

Showing posts with label organelle. Show all posts

Cellular Self-Sacrifice

Biology Concepts – apoptosis, synthaesthesia, mitochondria

We often ascribe human traits to objects that do not have thoughts or feelings of their own. This is called anthropomorphism, and it is hard to go through a day without committing this faux pas.

Anthropomorphism is difficult thing to avoid. We are thinking

beings, and we look at other organisms as if we were them –

so we assign our thoughts to them. A typical example would be

the belief that bacteria and viruses MEAN to do us harm, they

have an evil intent when the infect us. It’s just not so……. except

for athlete’s foot fungus. If you have had it before, you know that

it means to make your life miserable.

It is especially difficult to avoid in biology, even scientists will say that an organism “decides” to do this or an enzyme interacts with a substrate “in order to” accomplish that – the enzyme doesn’t have an agenda, it is just chemistry and physics. Assigning feelings or motives to biological entities is often a way to help explain a concept. As long as everyone agrees that it is just a technique, I think it’s fine. The problem arises when not everyone understands that its just a verbal crutch and they start to internalize it.

I can think of one case in particular where individual cells of a multicellular organism seem to be acting with a purpose, even a sense of altruism. It is called apoptosis or programmed cell death. In apoptosis (from Greek meaning, “falling off”) a cell will die “in order to” contribute to the overall health of the organism. It happens all the time. Autumn is full of apoptosis, as this is the mechanism of leaves falling, and is where the original word came from.

You just had about 1 million of your cells die as a result of apoptosis! … There! It just happened again! About a million cells/sec “commit suicide” (there’s some more anthropomorphism) so that you can live. If they didn’t die, you would.

It starts early, when you were in your embryonic stage. Your hands and feet started as single masses, with the bones growing in the appropriate places, at 48 days the skin covering is them all was one unit, more of a mitten than a glove.

In utero, your hands develop with individual fingers, but covered

by tissue all over, then apoptosis divides them into individual

fingers. The same thing happens with your toes…. Unless it doesn’t

work as it should. If it doesn’t, you end up with syndactyly, or fused

digits.

Then some of the skin cells between the digits began to die, and your fingers and toes started to become apparent. Sometimes the process doesn’t work completely, and people will have webs between their fingers or toes, or two digits will be fused together completely (syndactyly, syn = same and dactyl = digit). In the normal case, these skin cells are programmed to die. Why have the cell in the first place if it just going to die?

In terms of fetal formation, the cells do serve a purpose when they are formed, but that purpose is only temporary. However, this is not unlike many of your adult cells. The cells dying inside you right now probably had a “job to do,” but now they are worn out and replacements have been made for them. In essence, most of our cells are temporary.

Apoptosis is a group of complex mechanisms that allow cells to die well. We all know about cells that do not die well. If you hit your thumb with a hammer, you kill a few thousand cells. They tear open and dump their cellular contents into the tissue around them. This signals a reaction called inflammation and perhaps a sort of immune response. Inflammation and immune responses are good at cleaning up the damage, but they can cause damage in the process. With a million cells dying every second by apoptosis, you would never survive if every death brought an inflammatory response.

Necrosis is the cell death with inflammation and tissue

destruction. This is what happens in frostbite. Can you

imagine if you had this sort of reaction when undergoing

apoptosis to make your individual fingers in utero?

Dying well means cell death without inflammation. In apoptosis, the mechanisms work to shrink the cell away from its neighbors but keeps the cell membrane intact for most of the time it is dying. This prevents the inflammatory response from being jump started.

Signals from outside the cell can stimulate apoptosis, including hormones, damaging chemicals, or a loss of innervation. Sometimes it can be as little as a cell migrating from where it should be; the lack of the proper neighboring cells triggers the out of place cell to die. These are examples of extrinsic apoptosis.

But the signal could be intrinsicas well. Signals that come from inside the cell could be DNA damage, too many oxygen radicals causing damage to proteins, or even that the cell senses it has been infected by a virus. Viruses turn the cell into a virus factory, then the cell bursts to release the new viral particles and they go on to infect more cells. By initiating programmed cell death, no new viruses are made, so no additional cells will be infected and killed. As Spock would say, "They good of the many outweighs the good of the few, or the one."

The exceptional part about this process is that the mitochondrion is a crucial instigator in apoptosis. This organelle that is so crucial for life and so important for giving the cell its energy to carry out its functions, is one of the main checkpoints and instruments of programmed cell death.

If the signal for apoptosis comes from within the cell, it results in a change in the membrane of the mitochondrion, with leakage of a protein called cytochrome c out into the cytoplasm. Cytochrome c is usually held within the mitochondrion, so that the apoptosis process is held in check. Once released, this protein complexes with other proteins to form an apoptosome, and this starts a cascade toward death.

If the signal comes from outside the cell, many different receptors and pathways can be involved, but some of these will also affect the mitochondria. There are competing sets of factors in the cytoplasm, some always pushing toward cell death while others apoptosis from proceeding. The delicate balance of the factors that want to disrupt the mitochondrion and those that want to protect it allows the cell to live in harmony with itself until there is a reason to die.

This cartoon is a little detailed, but the take home message

is that many insults can lead to mitochondrial damage

(top arrows) and the damage can lead to several signals

for cell suicide – apotposis (bottom arrows).

The extrinsic signals can cause the balance to shift toward mitochondrial leak of cytochrome c. This leads to apoptosome formation, and this activates caspases and other executioner protein enzymes that will start to destroy the cell from within. Some enzymes cut up the DNA into small pieces so that it is no longer functional. Others force the chromatin and nucleus to condense and shrink (become pyknotic) and stop making ribosomes. Some digest important proteins in the cytoplasm. The sum total of their actions is a non-functional cell, but one that is still intact. Over time, the shrunken and dying cell is recognized by macrophages or other cells that quietly break it up and digest it, all without causing any inflammation.

Apoptosis isn’t just for your looks, as in giving you individual fingers and toes. It plays a role in every system of your body, in other animals, and even in plants. Plant cells undergo a programmed cell death, but it is a little different than animal apoptosis because they also have a cell wall to deal with and they don’t have an immune system to ingest all the dying cells. And the metamorphosis of caterpillars turning into butterflies and tadpoles becoming frogs… that couldn’t happen without a lot of apoptosis.

Your embryonic and juvenile nervous system has millions of neurons it does not need. The connections between some neurons may not be in accordance with how humans process signals, and some dying back of processes and cells is expected (called neural pruning).

Misplaced connections that do not die from apoptosis can lead to some interesting results. Synaesthesiais a group of conditions where sensory input is interpreted in more than one area. For example, if connections between taste and other parts of the brain are not pruned by apoptosis, some people will taste colors, or names will have a certain taste. Many synaesthetes (people with synaesthesia) will see number in their brains as having certain shape or texture. It is believed that most children have near photographic memories and cross innervations among the senses, but that the connections for these abilities die back in order to prevent sensory or memory overload.

It is unfortunate that there aren’t very descriptive pictures

that could show what it is like to have synthaesthesia – sure

you can show a colored word or set of letters, but you don’t

get the idea of what it is to see it in your head when your

hear a letter or word. This chart shows a little of how the

senses can be combine, each combination has a name, but I like

how Dr. Hugo Heyrman sums it up – Synesthesia is a love story

between the senses.

But this is not the only use of apoptosis in the brain. You have heard the expression, “use it or lose it?” This applies to your brain as well. Neural connections in the brain that are stimulated by experiences or thoughts get reinforced, and are less likely to undergo programmed cell death. Those connections that are not used when young are not kept; it would be a waste of energy.

Your immune system also relies on apoptosis. You have T lymphocytes that are designed to recognize a certain molecule that shouldn’t be in your body. Each population of T cells recognizes a different potential problem guest – millions of them in all. But some of the T cells that are made recognize a particle that looks a lot like one of your own molecules. You don’t want that.

In your thymus and other places in your body, your T cells go through a testing process. If they recognize a protein or molecule that isn’t you, they are allowed to mature and then go out in to the body and patrol for their particular target. But if they are programmed to recognize something that is “self” then they are signaled to undergo apoptosis.

It is a great system and works most of the time, but there are exceptions. Some “non-self” proteins can mimic “self” proteins, and if you start to develop an immune response to them, there may be some cross-reaction with your own cells. Or perhaps some T cells that recognize a “self” protein don’t undergo apoptosis when they should. These issues can result in autoimmune diseases – your immune system is attacking you.

Cancer is a loss of cell cycle control, including the idea that

cells are meant to die at an appropriate time. The problem

is that there are many ways that a cell can circumvent the

apoptosis signals, so you can’t induce apoptosis in all cancer

cells by using just one medicine. Plus, how do you tell the

cancer cells to undergo programmed cell death,
but tell the normal cells to stay alive?

So - too little apoptosis can be a bad thing. One other big example of this is cancer. Most cells have a life span, they should die at some point. But in some types of cancer, the mutations can tip the balance in the cell and mitochondria toward the survival end; they keep living and dividing and piling up; this is a tumor.

Death is a part of life, and we should be thankful for it.

For the summer months I will be posting shorter stories. I will talk about questions I have about biology that could also stimulate interesting discussion. I will also look into different experiments that any individual or group can perform and which can help to open our eyes to the wonders of how biology works. In the fall, more exceptional stories should be ready to help us understand the big ideas in biology.

For more information or classroom activities on apoptosis and synthaesthesia, see:

Apoptosis –

http://www.woodrow.org/teachers/bi/1997/apotosis/

http://www.lessoncorner.com/Science/Biology/Cell_Biology/Apoptosis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC256977/

http://www.ehow.com/how-does_5172524_steps-apoptosis.html

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Apoptosis.html

http://www.youtube.com/watch?v=wREkXDiTkPs&feature=fvwrel

http://www.cellsalive.com/apop.htm

http://www.celldeath-apoptosis.org/

http://www.promega.com/resources/product-guides-and-selectors/protocols-and-applications-guide/apoptosis/

www.roche-applied-science.com/PROD.../apoptosis_003_004.pdf

http://abstracts.aspb.org/pb1997/public/P64/0400.shtml

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CHYQFjAA&url=http%3A%2F%2Fjcmb.halic.edu.tr%2Fpdf%2F4-1%2FProgrammed.pdf&ei=9R7eT5ebCoim8gSK-pj3Cg&usg=AFQjCNEscW4eeiFGAzLuSE-mQAhR_xF3lw

www.plantsciences.ucdavis.edu/faculty/durzan/146.pdf

Synaesthesia –

http://faculty.washington.edu/chudler/syne.html

http://web.mit.edu/synesthesia/www/

http://synesthete.org/

http://www.mixsig.net/

http://nookkin.com/content/synesthesia.php

http://www.quibblo.com/quiz/1fOzV6O/Do-You-Have-Synesthesia

http://matthewjamestaylor.com/blog/synesthesia-associating-colours-to-letters

http://www.enotes.com/documents/synesthesia-worksheet-1139

http://www.psychologyinaction.org/2011/01/28/synesthesia-when-ordinary-activities-trigger-extraordinary-sensations/

http://www.awaytoteach.net/?q=node/5128&quicktabs_2529=0&quicktabs_2530=3

https://sites.google.com/site/synesthesiaresearchteam/

Biological Fusion Energy

Biology Concepts – mitochondrial dynamics

Stars are the largest fusion reactors around, and organisms do use

some of the energy our Sun produces by joining two hydrogen atoms

into a helium atom - remember photosynthesis? Fission reactors are

closer to home, but are much less efficient -- and can melt down

and kill us all. Cellular fission and fusion are about joining and

splitting things as well, just without the release of energy.

In the typical picture of a working cell, you would see millions of vacuoles traveling around, joining together and splitting off from organelles. The general proposition is that a bag of stuff fuses(joins) or fissions (separates) from another bag of stuff.

In physics, fission and fusion can be sources of great energy, but in cells they usually require an input of energy. If the processes were the same, we could run the world’s electronics on biology power – a true cell phone!

Fusing and fissioning are easy for vacuoles, they have one membrane. But the mitochondria and chloroplasts we have been looking at for the past few posts have very specific, double membrane structures. The outer membrane and inner membranes form a intermembrane space that is crucial for their function, and the inner membranes have specific forms and structures that are necessary to make carbohydrate or ATP.

Wouldn’t fusing or splitting these organelles destroy the membrane structures needed to maintain their functions? Indeed, the typical cartoon of the cell shows individual mitochondria or chloroplasts floating around in the cell, doing their jobs, but not interacting with the other organelles or with each other.

The structure pictured in green is, believe, it or not, the

mitochondrion of a fibroblast (fibro = fiber and blast =

sprout) cell, one that makes connective tissue. This doesn’t

look much like the mitochondrion in the biology books,

does it? The different strands join together and separate

constantly.

For mitochondria at least, this picture is misleading. In many cells, the mitochondria do not look like independent structures floating within the cell. They look more like strands of spaghetti on your plate. Mitochondria can also move around, they fuse together and break apart, they are recruited to different subcellular areas based on energy need, and they can exchange organellar content.

All these features (shape, communication, movement, fusion, fission, and exchange) are dynamic, meaning that they change with time and are regulated. First recognized as a regulated process about 10 years ago, this has spawned a new line of research called mitochondrial dynamics.

Changes in morphology are also involved in progression through the cell cycle. A 2009 study showed that in cultured cells, the mitochondria must fuse together into branched networks in order for the cell to enter the phase when it replicates its DNA. Now it appears that this changing mitochondrial morphology is important for other shifts in cell fate. The same group that conducted the 2009 study above showed in May 2012 that mitochondrial fusion and fission are important for oogenesis differentiation (the changes an egg goes through to become different types of cells) in fruit fly egg chambers, implying their importance in differentiation of other cells too.

It appears that fusion and fission help to maintain the correct number of mitochondria, but also work in the preservation of mitochondrial function. Defective proteins can be kicked out if there are normal proteins to replace them. Fusion of mitochondria can provide these normal proteins. In other instances, low oxygen or low carbohydrate concentrations can bring fission and fusion so that the mitochondria can share nutrients and prevent their own degradation.

Most importantly, defective mitochondrial DNA (mtDNA) can be minimized by combining or being replaced it with normal DNA from functioning mitochondria. In most cases, recombination of DNA serves to increase genetic diversity, but with mtDNA it seems the opposite effect is desired. Recombining and exchanging DNA serves to maintain a single uniform genome for all the mitochondria; fusion can preserve the integrity of the mitochondrial genome. Mutations or defects in either exchange, fission, or fusion systems result in poor mitochondrial function and identifiable diseases.

People with Charcot-Marie Tooth have very high

arches, and are most often double jointed. Would

you enjoy having your knees bend the other

direction? I can tell you from personal experience,

that double jointed people are very hard to wrestle

against. They can slip out of whatever hold you try

on them.

If the fusion of mitochondria is defective, a disease called Charcot-Marie-Tooth type 2a may result. This is a neuronal degenerative disease that usually affects the lower extremities more than the arms. Most cases are caused by defects in the cells that surround the neural axon (the long projection between the cell body and the connection point to other neurons), but in type 2a, the defect is in the axon, specifically the inability of mitochondria to fuse. Therefore, fusion must be important.

In Huntington’s disease, there is too much mitochondrial fission. Huntington’s chorea (chorea = dance, patients with this disease develop large uncontrollable movements that make it look like they are dancing). The cause is an expansion in the huntingtin gene (yes, I spelled it right); a three DNA base repeat (CAG) is mutated and becomes repeated too many times. This affects the function of the huntingtin protein. The age of onset and speed of progression are related to how expanded the triplet repeat is. As of today, this autosomal dominant genetic disease (only need to inherit one mutant gene for it to occur) is untreatable and fatal.

However, the mechanism by which this mutation causes neuron degeneration is just becoming clear. A 2010 study indicated that the mutant huntingtin protein interacts with the proteins that control mitochondrial fission and makes them overactive. Too much fission disrupts mitochondrial functions and the neurons become defective and then die.

Even more important, in terms of numbers of people affected, is the link between reduced mitochondrial fission and Alzheimer’s disease. Scientists know that it was the build up of amyloid protein that promotes neuron degeneration, but until recently, they didn’t know how it was occurring. It turns out that the plaque proteins can stimulate nitric oxide production, which then damages the fission proteins of the mitochondria.

DRP1 proteins are important for the fission of a

mitochondrion into two mitochondria. They oligomerize

(join together in groups) and pinch the mitochondria

apart. Nitric oxide can damage the DRP1 proteins – so

no mitochondrial fission.

This is huge news because preventing this nitric oxide damage might be a way to slow or stop Alzheimer’s progression. This is a difficult area of research, since nitric oxide is important in many biochemical pathways; just shutting down nitric oxide production everywhere in the body would lead to defective hair growth, blood vessel pressure control, abnormal blood clotting and atherosclerosis, ……oh, and Viagra wouldn’t work either.

The movement of mitochondria within cells is also crucial for their function. The longest cells in your body are your motor neurons. A single cell can be several feet long. Your mitochondria must get to where they are needed along the axon of the neuron, and this requires regulated transport and communication.

Defective transport is one outcome during Charcot-Marie-Tooth type 2a defective mitochondrial fusion and in overstimulation of mitochondrial fission in Huntington’s disease. In addition, defective axonal transport of mitochondria may turn out to be an important early defect in Alzheimer’s disease. In fact, defective transport of mitochondria may play a role in Parkinson’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease) and other neurodegenerative diseases that involve defective mitochondrial fusion and fission.

Why might this be….. I’m not sure, but here is a guess. Defective fusion or fission leads to defective function – defective function leads to reduced ATP formation – reduced ATP results in defective energy-requiring functions of the cell, like transport of mitochondria from one place to another. I have no evidence for this, but it is a logical, testable hypothesis. It could be that defective transport is an effect, not a cause, of these diseases -at least in part.

Two of our more famous Parkinson’s patients;

Muhammed Ali and Michael J. Fox. Float like Marty
McFly and sting like a bee?

For Parkinson’s disease, a 2009 study showed that defective mitochondrial transport occurred due to dysfunction in the fusion/fission system, independent of changes in the ATP level. However, ATP production is not the only function of mitochondria. They also work in regulating the amount of calcium in the cell, and altered calcium levels can lead to disruption of the cytoskeletal transport mechanisms. Maybe I need to tweek my hypothesis; it is fusion/fission-mediated defects in several mitochondrial functions that then cause axonal transport changes that are noted in many neurodegenerative disorders. Now design an experiment to test it - this is how scientists go about their work.

So we see that the mitochondria are not static, they are changing all the time and that these changes are crucial for their function and integrity. Here is our exception in the similarities of chloroplasts and mitochondria. It would seem, at least based on current evidence, chloroplasts are relative loners.

This is not to say that can’t be dynamic. We have seen that chloroplasts have a definitive inheritance pattern, either maternal or paternal, and they will fight to maintain this pattern. Chloroplast fusion has been most often described in the zygote(initial cell formed by fusion of the gametes during fertilization, from Greek zygota = joined or yoked together) of algae. In these cases, which are still rare, the chloroplast genome of one of the two fused organelles will be degraded. Fusion of other chloroplasts, as in mature plant cells, either does not occur or has not been studied, because I can’t find any publications describing it.

These are examples of the dynamic activities of chloroplasts.

Stromuleconnections can be formed between chloroplasts for

the passage of organelle contents. They are usually 0.5 microns

in diameter (1/500,000 of a meter) and can be found in all types

of plastids. Their function – not completely known yet.

On theother hand, chloroplasts aren’t complete loners either. As far back as the 1960’s there were reports saying that chloroplasts might have certain connections at certain times. More recent studies indicate that small connections can be formed between chloroplasts, often called tubular connections or stromules. It is interesting that stromules can be formed between chloroplasts and mitochondria. It is believed that this is one way the plant cell keeps these two organelles close to one another, since their functions, products, and by-products are so interrelated.

You might ask why the mitochondria and chloroplasts that have so much in common differ in their relative dynamic properties. They were both once free organisms that had to have lots of interactions with other members of their species, but only the mitochondria seemed to have preserved it. Next week, we will look into how this mitochondrial dynamism is even more crucial organism survival – by regulating cell death. Believe it or not, cells have to know how to die well.

Kasturi Mitra, Richa Rikhy, Mary Lilly, and Jennifer Lippincott-Schwartz (2012). DRP1-dependent mitochondrial fission initiates follicle cell differentiation during Drosophila oogenesis J Cell Biol DOI: 10.1083/jcb.201110058

For more information or classroom activities on mitochondrial dynamics or cellular differentiation, see:

Mitochondrial dynamics –

http://mitodyn2011.azuleon.org/

http://www.its.caltech.edu/~chanlab/main%20pages/research.html

http://www.youtube.com/watch?v=0NmBaw3grr4

http://www.plantmitochondria.net/Plant_Mitochondria/Movies.html

http://www.nature.com/scitable/topicpage/mitochondrial-fusion-and-division-14264007

http://biology.about.com/b/2010/04/23/mitochondrial-fusion.htm

http://www.sciencedaily.com/releases/2010/04/100415125942.htm

http://www.sciencedaily.com/releases/2011/01/110124162712.htm

http://www.ellisonfoundation.org/content/does-mitochondrial-fusion-protect-against-mitochondrial-dna-mutations-during-aging

www.its.caltech.edu/~chanlab/PDFs/Griffin_et_al_BBA_2006.pdf

https://research.uiowa.edu/arra/project/176

The Evolution Of Cooperation

Biology concepts – biological timeline, serial endosymbiosis, endocystosis, evolution

Taxonomy, the placing of species in different

groups based on their characteristics, changes

everyday – literally everyday – organisms are

placed in different groups and groups are created

and eliminated. That better be a temporary tattoo!

If we look at the 3.5 billion year history of life on Earth, we see that out planet was lifeless for almost a quarter of its span, and animals have been around just a short blip of time, a mere 760 million years. Often, it seems that the big numbers to get in the way of understanding the time line as a whole.

If we treat the entire history of earth as one year, we might get a clearer picture. Earth coalesces from space dust on January 1^st, but it isn’t until March 22nd that we find the first evidence of life. These most primitive fossils are of the prokaryotes called Archaea (Greek for “ancient”). Not long after this, maybe a week or so, the eubacteria and Archaea separate from one another.

Then we have to wait until August 7^th to find a big change; the first eukaryotic organisms are seen. These represent a fundamental change in the organisms, having nuclei and membrane bound organelles. It's amazing that we must travel 3/4 through our one year time line before we see a cell that looks somewhat like ours!

Here is one of the Namibia sponge fossils recently

discovered in Africa. It represents the oldest animal

in the fossil record. Just how that was recognized as a

fossil is beyond me – I think I have six of those in my

garden!

Later in the year, around October 30^th at noon, we see the first animals. Fossils of Namibia sponges in Africa were first reported in February of 2012. This fossils are 100 million years older than the previously oldest animal remains, so our new data means that animals have been around for an additional week in our time line of a year.

Insects appear about Nov. 26^th, while mammals first show up around Dec. 8^th. The dinosaurs became extinct sometime in the afternoon of Dec. 26^th, so they had very little time to play with their Christmas presents. Homo sapiens (us) didn’t appear on the doorstep looking for holiday cheer until 11:40 pm on New Years Eve, Dec. 31^st!

Our time line analogy shows us that prokaryotes are the wise old ancestors; we aren’t even old enough to be rebellious teenagers, although we still think we know everything. The key question is: how did we progress to analogy-makers from single celled Archaea? If we put together several of the topics we have been discussing in the past three weeks, we may come up with an interesting step in the process. Our clues include:

1) Microcompartments exist in bacteria, like organelles, and they also exist in eukaryotic cells, especially in nucleus' function. This links eukaryotes to prokaryotes.

2) Sometimes cells will engulf objects, parts of other cells, or other cells. Depending on the size of the particle or cell, we may call this endocytosis or phagocytosis, and is similar to how we saw keratinocytes take up melanosomes.

3) Three eukaryotic organelles, the nucleus, the mitochondria, and the chloroplast have double membranes, and they each have their own DNA.

4) There are two different types of prokaryotes, archaea and bacteria.

Bacterial microcompartments give prokaryotes some compartmentalization in order to carry out necessary chemical reactions. Eukaryotes also have some prokaryotic microcompartment remnants, like the nuclear vault complex. This shows crossover between prokaryotes and eukaryotes, and gives us clues about eukaryotic origins. In fact, the currently accepted theory about the evolution of organelles - the very thing that makes cells eukaryotic - has to do with both types of prokaryotes - archaea and bacteria.

There are three types of endocytosis (with exceptions).

Endocystosis of large objects and cells is called phagocytosis.

Internalization of very small molecules and fluid is called

pinocytosis. Other molecules of various sizes have specific

receptors that recognize them on the cell surface. They are

brought in by receptor-mediated endocytosis. Notice that no

matter what method is used, the internalized particle ends up

surrounded by part of the cell membrane.

The key to their interrelationship has to do with endocytosis (endo = into, cyto = cell). Most prokaryotic and eukaryotic cells eat other cells; they do it all the time – it is how heterotrophic organisms (those that can't make their own carbohydrates, ie. non-plants) gain their nutrients. We do it too, just on a larger scale; we eat millions of cells at a time; often these millions of cells can take the shape of a steak or a carrot.

When a cell, protein, other molecule is engulfed by another cell, it is wrapped in a portion of the aggressor cell’s membrane. The naked molecule is now contained in a vesicle, a membrane bound sac, like the melanosome. If the endocytosed material is an entire cell, something that has its own membrane, then it ends up with two membranes, just like the mitochondrion, chloroplast, and nucleus.

Most often, when one prokaryote phagocytoses another, the story is over….gulp, yum, digest. But scientists believe that long ago (sometime in the first week of August in our time line) an endocytosed cell did not go gentle into that good night. Instead, it took up residence in the cell that ate it. In this rare case, it turned out that both cells gained from the situation.

The endocytosed cell was protected from other predators and had a ready supply of nutrients from the parent cell. The captured cell made lots of ATP, but it didn’t need much because it was being supplied with everything it needed; it didn't need to make energy to move or hunt or escape. Most of its ATP production went unused. Perhaps it moved this excess ATP out into the parent cell. So the parent cell gained a source of ATP production. This was mutualism, a type of symbiosis in which both parties benefit.

Clownfish clean the sea anemone and keep it

parasite free. The poisonous anemone provides

a safe environment for the clown fish; no

unwanted house guests! This is a good example of

mutualistic symbiosis. Bet you didn’t know you

learned things from Finding Nemo.

Imagine if the same thing happened with a cyanobacterium, a cell that could perform photosynthesis. The same sort of symbiosis might be set up, with the endocystosed cell providing carbohydrates and the parent cell providing protection.

Now imagine that these captured cells, the photosynthesizer and the ATP maker, replicated themselves inside their parent cells just as they would if they were outside, living on their own. They could easily do this since they still retained their own DNA and cell division mechanisms.

This is in fact what scientists believe happened. The endocytosed cells that produced extra ATP evolved into our mitochondria. Endocytosed cells that could do photosynthesis became the chloroplasts of plants. Not all cells are plants because not all cells with an ancestral mitochondria also ate a cyanobacterium. The fact that plants cells have mitochondria as well as chloroplasts tells us that plant cells developed AFTER cells with mitochondrial ancestors.

But the nucleus may be a tougher nut to crack. It may be that an endocytosed cell good at keeping DNA safe and producing ribosomes became the nucleus, by endocytosis. The data suggests that our DNA is closer to archaeal DNA than bacterial DNA, so it would have been a eubacteria endocytosing an archaea. Or perhaps the archaea invaded the bacterium rather than being endocytosed. The nucleus does have a double membrane and uses some prokaryotic microcompartments to this day, so this could make sense.

But other theories also exist, including one that says an intermediate eukaryotic cell, theoretically called a chronocyte, had developed some organelles on its own or by endocytosis, including a cytoskeleton. This internal structure allowed the cell become bigger, and engulf a cell large enough to evolve into the nucleus.

Another theory uses an evolutionary exception as its basis. Some aquatic bacteria, called planctomycetes (planktos = drifting and mycete = fungus-like), have an organized interior, with something that looks like a nucleus with pores, called a nucleoid. In fact, when they were first discovered, planctomycetes were mistaken for small fungal cells. However, we know they are prokaryotes by DNA sequencing. I thought prokaryotes didn’t have nuclei! Remember that in biology, there is almost always an exception. The planctomycete nucleoid structure suggests that the nucleus may have evolved on its own, without endocytosis.

The planctomycete species, Pirellula (latin for small pear),

is an exceptional bacterium. It has a primitive nucleus

and a stalk that makes it look like a eukaryotic

fungal cell. It was misidentified for a long time, and is

a prime example of why the tattoo above was a bad

idea!

Finally, another theory posits that the nucleus originated from a virus infecting a primitive prokaryote, and this internalized virus forming a nucleus or causing the cell to be predated by another cell. Even though there are different theories for the nucleus, we can see that the three organelles that have double membranes look like they could have been endocytosed cells, that then evolved into the organelles we see today. Endocytosis resulted in symbiosis, so the theory of organelle development is called endosymbiosis.

Endosymbiosis is a cool idea and has lots of support. Besides the double membrane evidence, lets look at how dividing cells get more mitochondria and chloroplasts. These organelles replicate on their own by binary fission, just like bacteria. They can replicate on their own because they have their own DNA. Mitochondrial DNA (mtDNA) and chloroplast DNA (chDNA) are smaller pieces of DNA than nuclear chromosomes, mtDNA and chDNA look much like the small genomes of bacteria. They are also circular pieces of DNA, not linear like our nuclear chromosomes.

By replicating through binary fission, they can be portioned in the dividing cell so that each daughter gets some of these crucial organelles. But it isn’t as if mitochondria and chloroplasts of today look just like the engulfed ancestors. Mitochondrial and chloroplast genomes are greatly reduced from what they used to be.

Serial endocytosis is also called secondary (2˚) endocytosis.

This refers to the movement of DNA from internalized

cells to the nucleus of the endocytosing cell by lateral

gene transfer. This strengthens the symbiotic relationship

between the two organisms until they can be considered

one total organism.

The mitochondria only codes for about thirteen proteins, just enough for it to replicate on its own. The DNA that codes for the rest of the 1500 or so proteins needed for mitochondrial function have been transferred to the nucleus over time. For a discussion of the chloroplast and its horizontal gene transfer to the nucleus, see the posts on C. litorea, the photosynthetic sea slug.

We know that these gene transfers were actual events based on the structure and nucleotide ordering of the mitochondrial and photosynthetic sequences in the eukaryotic chromosomes; they are structured and coded in ways that are typically bacterial. Because of this slow transfer of DNA to the nucleus, endosymbiosis has evolved over time, changing again and again until we got today’s organelles. Therefore, our idea of organelle development is sometimes called serial endosymbiosis theory (SET), because it must have had several different changes through evolution.

Now that we have laid out the evidence and sense for the serial endosymbiosis theory, next week we can talk about some exceptions that show us that that some organisms just can't stick with something that seems to work. Some life just has to take the road less traveled.

For more information or classroom activities on history of life time lines, endocytosis, serial endosymbiosis theory, evolution of eukaryotes, or planctomycetes, see:

History of life on Earth timelines -

http://exploringorigins.org/timeline.html

http://www.bbc.co.uk/nature/history_of_the_earth

http://www.scientificpsychic.com/etc/timeline/timeline.html

http://www.lifethroughtime.com/experience.html

http://dsc.discovery.com/earth/wide-angle/mass-extinctions-timeline.html

http://www.acad.carleton.edu/curricular/BIOL/classes/bio302/pages/IntTimeline.html

http://serc.carleton.edu/quantskills/activities/calculatortape.html

http://www.mysciencebox.org/timelines

www.saskschools.ca/.../timeline/biologicaltimeline/teachernotes.rtf

www.jessb.org/blog/.../Timeline%20description%20and%20setup.pd

http://www.nclark.net/HistoryLife