The cells have to squeeze through really fine capillaries, which would probably be more of a problem, if they had a nucleus. It might also avoid oxidative damage of the DNA. RBC are not getting very old anyway (around 120 days if I remember correct), so the turn-over is quite high.

the main function of RBCs is to carry oxygen with the the help of Hb. RBCs are non nucleated in order to store greater amount of hemoglobin.

Disadvantage: cannor replicate due to absence of DNA found in nucleus. but, RBCs are present in large amount about 5 million.

So, the main purpose of RBC is solved.

Before maturity RBCs are nucleated (with DNA). this helps in growth of RBCs. At this stage, their main function is growth not Hb carrying.

The cells have to squeeze through really fine capillaries, which would probably be more of a problem, if they had a nucleus. It might also avoid oxidative damage of the DNA. RBC are not getting very old anyway (around 120 days if I remember correct), so the turn-over is quite high.

120 days without nucleus is a very long time ! I think RBC must be investigated very in depth in terms of gene expression regulation, clearly no 'transcription regulation' is possible and all the cell's life (after all an RBC must kkep alive its memebrane, have a metabolism and so forth..)long regulation must be in some sense 'predicted in advance'..I imagine a large use of post-transcriptional cues, clearly no chromatin modifier...well in any case a crucial system to investigate !

Good answer Christian P.

Unlike many other cells, red blood cells have no nucleus and can easily change shape, helping them fit through the various blood vessels in your body. The lack of a nucleus makes a red blood cell more flexible, and also limits the life of the cell preventing cells "damaged" (e.g. the permanent bond with molecules such as CO) to persist too long in the organism, impairing oxygen distribution.

The lack of a nucleus allows more room for hemoglobin, and the biconcave shape

of the red blood cell helps increase its oxygen-carrying capacity but it should be mentioned that unlike mammalian cells, red blood cells of amphibians, reptiles, and birds retain a nucleus in maturity. Also,Fragments of the nucleus, or Howell-Jolly bodies, are normally seen in a few circulating red cells of the horse and cat.

None finds intriguing a cell living so much without DNA ????? How it is possible to cope with all the bla-bal on transcription control, chromatine re-arrangement, operons, feedback...how it can be such a strange way of living ? What we can learn more in geenral on the plasticity of regulation that can give rise to a viable cell without what is considered the 'main actor' ?

I am not so sure I agree with the above comments about the need to change shape and accommodate large amounts of Hb. If this were the case then I would have thought that birds who in general have higher O2 demands than mammals would have evolved anucleate blood cells as well - they are after all a more ancient lineage than mammals and so have had considerably longer to evolve anucleate blood cells it it were so advantageous.

I think the 'why' questions are largely not decidible in biology (this is not the case for example in chemistry where valence rules and energy considerations give a frame for answering such questions), basically the same problem in biology can be solved in many different ways with no evident 'constraints'. I think that the 'how' questions can be much more fruitful in biology, this is why I tried and stimulate the discussion of 'how' a cell without nucleus can maintain for so a long time an homeostatic behavior without having the possibility to refer to its genetic material...

Mature human RBCs represent a stage of cellular existence totally dedicated to service - giving oxygen to other cells and taking away life-threatening carbon dioxide away - even to the extent losing their identity expressed by DNA/nucleus.

Well this is very intriguing but in my opinion this is too poetic, even a person completely dedicated to service must think of his/her homeostasis, and has an identity !

In other words a cell is a cell and must stay alive in order to carry hemoglobin (or doing any other service for the entire organism)so the cell must have its own metabolism, must keep the integrity of membrane and cytoskeleton and for doing so we are used to think a given amount of 'transcription regulation' involving the DNA in the nucleus is necessary..but RBC has no nucleus...

Traces of functional DNA might provide the "housekeeping" transcription necessary to keep the cell living and well for the time it has to live, I don't know if this has been documented. Although it must be noted that these cells do little energy requiring work, as most of the elements that they carry enter and exit the cell flowing on a concentration gradient.

As Jalali pointed out, other vertebrates have RBC with nucleus, and it would shed some light if someone knew how much time they live.

If this hypothesis of 'traces of functional DNA' keeping the housekeeping genes could be validated it should be incredibly interesting because it encompasses a sort of 'supervisor' system able to select the 'minimal set' of genes to make RBC to live. As a matter of fact even the embryos for the first divisions do not use their 'new genetic material' and rely on the RNAs of mother origin but they live in a very well protected situation and they do not go around for 120 days in that situation...

I did a google search and this very old paper speaks of a directly enzymatic regulation:

http://www.sciencedirect.com/science/article/pii/0304416569900993

this more recent paper shows an unsuspected complexity of RBC proteome with a lot of regulation activities ongoing:

http://bloodjournal.hematologylibrary.org/content/108/3/791.short

Moreover RBC are an environment allowing plasmodium (malaria parasite) to live and this implies a very fine tuned co-regulation of host and parasite:

http://www.sciencedirect.com/science/article/pii/S0014579306010301

I'm wandering if someone has studied in depth the biological regulation in this strange 'without DNA' or 'still more intriguing' 'with only minimal DNA carefully selected by some intelligent trimmer'...if someone is there I will like he/she to participate this forum...

RBCs are cellular example of minimalistic requirements and maximum service in human body and final dissolution into the body after 120 days of dedicated job. They represent an existence where science, philosophy, and psychology meet - like a yogi renouncing ego and serving societly selflessly wearing a 'saffron' (hemoglobin-like colour) shroud. Enjoy the incidence, coincidence of from individual to molecular level.

I don't agree on the intelligent trimmer, but if in fact there is residual DNA that transcribes needed proteins, it should be relatively simply to find out.

On this I found this study http://www.medsci.org/v06p0156.htm

Tey report functional RNA transcripts with many genes, which might mean the RBC carry a load of RNA that is the responsible for keeping it running. Fascinating!

Juan

Good paper link. yet, it does support a minimalistic active gene-support in mature human RBCs; RNA for protein synthesis and associated wherewithal is not un-expected for RBC's life-time service of 120 days. Extra-nuclear genes are no exception to the rule. Cellular identity is represented mainly by the nucleus in eukaryotes. Cheers!

Dear Juan,

thank you for your points and the incredibly interesting paper you inserted the link, it is very strange such a potentially revolutionary paper appears in a relatively minor publication (but at a second thinking perhaps is not so strange) I noted a very intriguing point, the authors say:

Recent proteomic studies of RBCs based on 1D/2D-electrophoresis 6, 7 or mass spectrometry assay 8, 9, allowed to recognize 272 proteins. Our data generated from microarray studies (n=7) evidence the presence of transcripts for 1019 genes in RNA of human RBCs including the above mentioned 272 proteins. The complete array dataset with genes reported has been deposited in the Gene Expression Omnibus database (accession number - GSE3674).

It was found 529 genes for cellular metabolism (among them 96 genes for protein biosynthesis), 228 genes for signal transduction (among them 112 genes for intracellular signalling cascade), 104 genes for development, 107 genes for immune response, 62 genes for protein localization, and only 53 genes for programmed cell death as well as 5 genes for autophagy. The function of remainder (160 genes) is yet unknown.

In the first paragraph they correctly state they found the 'transcripts for 1019 genes', in the second paragraph the simplification was too drastic and possibly inducing in error 'It was found 529 genes..' this phrase makes us to think that THERE IS DNA INSIDE, AT LEAST SOME TRACES, but the results only refer to RNA molecules. No experimental result is reported giving evidence of the presence of DNA molecule...

The reason that human mature red blood cells lack a nucleus appears to be so that the red blood cell has room for more hemoglobin and therefore can carry more oxygen per cell. Remember the human red blood cells don’t always lack a nucleus. Up until the final steps of red blood cell maturation, they do have one.

..yes but the point is their actual life when the nucleus is absent, a cell life without nucleus must take into account an 'already wired' regulation for relatively long times (months)...this is in my opinion the puzzling thing to elucidate...

The lifespan of erythrocytes in  amphibians and reptilians is long. A frog -200days, the marine toad - 700-1400days, the box turtle 600-800 days.

The maximum life span of the chicken erythrocyte was found to be 35 days, of the pigeon erythrocyte 35-45 days, and the duck erythrocyte 42 days.

Human - 120 days.

Interesting!

I was wondering what could be trigger factor that allows for the damage/ enucleation of the DNA or the nucleus as a whole. Could not find any research on similar grounds. If someone finds something, could they please share it here?

On progressive accumulation of haemoglobin there is a decreased nuclear activity due to densening and condensation of chromosome. As a result, the dense genetic material moves to one area of the cell towards the periphery and asymmetric mitosis happens, creating an reticulocyte (containing nucleus) and a pyrenocyte (containing most of the cytopasmic content). The nuclear shift happens in an area where there is abundance of macrophage receptors, as the nucleus containing reticulocyte is then engulfed by the macrophage and what remains is the cytopasm rich pyrenocyte having maximum amount of Hb.

Source: Erythroblast enucleation, Haematologica, 2010.