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How did the red blood cell in humans get to lose its nucleus (and other organelles)? Does the bone marrow just not put the nucleus in, or is it stripped out at some stage in the construction of the cell?

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Red blood cells are initially produced in the bone marrow with a nucleus. They then undergo a process known as enucleation in which their nucleus is removed. Enucleation occurs roughly when the cell has reached maturity. According to one research (Ji, et al., 2008), the way this occurs in mice is that a ring of actin filaments surrounds the cell, and then contracts. This cuts off a segment of the cell containing the nucleus, which is then swallowed by a macrophage. Enucleation in humans most likely follows a very similar mechanism.

The absence of a nucleus is an adaptation of the red blood cell for its role. It allows the red blood cell to contain more hemoglobin and, therefore, carry more oxygen molecules. It also allows the cell to have its distinctive bi-concave shape which aids diffusion. This shape would not be possible if the cell had a nucleus in the way. Because of the advantages it gives, it is easy to see why evolution would cause this to occur. However, since little is known about the genes the control enucleation, it is still not a fully understood process.

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Are there references for the second paragraph? –  kmm Feb 14 '12 at 16:37
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I can't find any references to journal articles, but the facts mentioned are often stated in text books or lecture notes. For example: faculty.ucc.edu/biology-atsma/misc/blood.htm –  EdoDodo Feb 14 '12 at 17:32
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It's too bad they don't have citations. It would be nice to get away from just so stories and have a real evolutionary answer. –  kmm Feb 15 '12 at 1:12
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I don't have access to the full text, but this article proposes resistance to oxidative stress as a reason for enucleation: Red blood cell extrudes nucleus and mitochondria against oxidative stress –  nico May 8 '13 at 12:15
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It's a matter of geometry and physics. The nucleus is a huge volume of the red blood cell. Without the nucleus, its tissue-specific cytoskeleton arrangement allows it to form a bi-concave disc morphology. This disc shape also maximizes its surface area to volume ratio for maximized gas exchange, as well as affording the immense flexibility when squeezing and pinching through capillaries. –  leonardo Jun 26 '13 at 1:58
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The only function of the red blood cell is to transport oxygen, nothing else. It's concave shape is to increase its surface area, so more oxygen can be transported per cell. The absence of a nucleus means it can be significantly more concave than an other cell of analogous size, meaning it can carry more oxygen.

Other answers are more detailed, but this is the main reason that there is an absence of a nucleus.

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just to add on to the previous reply...

Shown to be in mice & rats (and sick humans), the cell-cell interaction between a macrophage (this is a big engulfing cell required for immunity) and young red blood cells (RBC), is known as the erythroblastic island (commonly known as EBI). If u googled it, there is a scientific review in 2008 that describes this structure.

At the embryonic stage (in humans), we still retain our RBC nuclei. But as we developed into fetus and adult, we no longer have RBC nuclei. This is thought to be related to the EBI present (in the fetal liver and adult bone marrow respectively). Currently, there is a lack of information of the EBI in other mammals. The only proven ones are mice, rats and sick humans. It is widely assumed (not proven) that mammals have EBIs. Besides mammals, some other animals (e.g. birds) have enucleated RBC, and some dont. It is unclear why is it so. Our lab thinks that it might be related to the formation of the EBI.

In addition to engulfing the RBC nuclei, it is believed that the macrophage acts as a "nurse" cell as proposed in the 50s. In other words, possibly providing iron, and possibly providing some proteins required for young RBC to mature. In early 2013, for the first time, it was showed that these macrophages are important in animal models(published by 2 research groups in nature medicine journal).

As for enucleation (the removal of erythroid nuclei), the exact mechanisms are unknown. But cytoskeleton proteins are important players in enucleation. However, there isnt enough information, as these proteins are essential for other important cellular activities as well. For example, bringing in nutrients, development and cellular migration. Most animal models that lack these proteins are unavailable for studies, and these animals usually die at the embryonic stage.

The research mentioned by EdoDodo is a proposed model on how enucleation takes place, and is a widely accepted model. Currently, our lab are working on another model that could partially explain how enucleation is being triggered.

Advantages of enucleation: In addition to better oxygen diffusion across the membranes, some older scientific papers mentioned that it lightened the cardiac workload. Each extruded RBC nuclei is approximately 40 picograms. A normal healthy adult individual would produce about 2 million RBC per second. That would be 0.08 milligrams of weight per second are required to be removed. However, I couldnt trace the scientific evidence for this claim, but this have been cited by some scientific papers.

The other advantage would be to reduce risk of hemolysis when transversing through the microvasculature. In other words, mature RBC can move along tiny blood capillaries by changing their biconcave shape (to bell-shaped I think), so that they will not rupture (and die).

I hope this helps.. :)

P.S. I forgot to add that, not all RBCs have similar shapes and sizes. You might want to google it for more information. I think camels have slightly different RBC morphology.

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I checked for the publications you mentioned here. I did not find any publication for macrophages and EBI in Nature Medicine, but I found two reviews from 2008 about EBIs: The Erythroblastic Island and Erythroblastic islands: niches for erythropoiesis. In case somebody wants to read them: they are freely available. It would be nice if you could add the other two papers, too. Thank you! –  suvidu Jan 16 at 16:26
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