MadSci Network: General Biology

Re: What is the smallest living thing?

Date: Tue Sep 25 12:14:37 2001
Posted By: Mike Conrad, Post-doc/Fellow, Microbiology, UNC
Area of science: General Biology
ID: 1000020168.Gb

What is the smallest living thing?

This question is controversial and it is also a subject of endless discussion, since we also need to know "What is life?". For this answer, I'll begin with bacteria, which are undoubtedly alive.

What is the smallest free living organism? Most bacteriology textbooks say Mycoplasma genitalium is the smallest known organism capable of independent growth and reproduction. Its size is given as 0.2 to 0.3 µm (micrometers). A µm is one millionth of a meter (or one thousandth of a millimeter). An average bacterium, like E. coli, is about 1 µm by 3 µm (it has a rod shape). A red blood cell is 8 µm in diameter and the average human cell is about 25 µm across.

Although mycoplasma can live in complex media in the laboratory, in nature they are always found living parasitically, attached to other cells. Since they take preformed nutrients from other cells, they have streamlined their metabolism and only have about 470 genes to use to make all the proteins needed for cell division, energy production, and protein synthesis, etc. These are the simplest cells found so far.

Other small bacteria are rickettsia and chlamydia which can be as small as 0.3 µm. But it's a big world, and probably fewer than 1% of the total bacterial strains have been characterized. That means there are many bacteria that have never been seen, or have been poorly studied. For instance, the marine ultramicrobacteria, Shingomonas sp strain RB2256, has been reported to be able to pass through a 0.22 µm ultrafilter. It should be noted that many bacteria, in response to starvation, go to a dormant state of much smaller size.
( It is not clear how many of these "ultramicrobacteria" represent nutrient downsized bacteria.


In 1990, Bob Folk at UT, using an electron microscope, observed 0.05 µm (50 nanometers) "nanobacteria" in rocks from hot springs. Nanobacteria were later found in blood, kidney stones, and in meteorites that came from Mars. Of course, this created quite a stir. But other researchers have not been able to find DNA or protein in nanobacteria, and it may be that the objects seen in the electron microscope are mineral microcrystals. Because of this, many experts doubt the existence of nanobacteria (see Nature (2000) 408, p394). But, supporters continue looking for evidence that nanobacteria are living.

A theoretical discussion of what could be the smallest bacterium possible gives a diameter of 0.17 µm This figure also precludes the possibility of nanobacteria. This nas nanopanel site has an excellent series of articles on the size limits of organisms.

Viruses are DNA or RNA that are unable to "live" without invading another cell and they use the molecular machinery of the host cell for metabolism and replication. "Are viruses alive?" is a philosophical question. They certainly have a life cycle and many would say that they are alive when they are infecting a cell. But whether they are alive or not, they don't have to carry around all the genes needed for an independent existence. Therefore, viruses can be very small, from 0.3 µm to 0.02 µm, or 300 to 20 nanometers (nm) in size. Picorna ("little RNA") viruses, like polio, are only 30 nm in diameter. Other viruses, like Parvoviruses, are just a linear single strand of DNA in a capsid with no extra proteins. Parvovirus DNA can be less than 5000 nucleotides long and the Parvoviruses can be as small as 20 nm in size.

And then there are viroids. Viroids are small circular single strands of RNA that lack a protein coat. To date, they have been shown to only cause plant diseases. Their RNA can be as short as 248 nucleotides long (80,000 molecular weight), which can be less than 10 nm diameter.

What about prions? Prions are thought to be infectious protein particles that cause several diseases in humans and animals, including Mad Cow Disease. The latest theory is that Prions recruit proteins similar to themselves in the membranes of brain cells. By lining up next to these proteins, they cause a conformational change that converts these brain proteins into Prion proteins, which are about 30,000 molecular weight, or about 5 nm. (These proteins can't be broken down by the cell, so they form aggregates that clog the cell.) It might be a stretch to say that prions are alive, but for completeness, here they are. Somewhere from prions to bacteria you can say life starts, and there are the sizes.

A word about methods for determining sizes. Standard methods to determine the sizes of bacteria and viruses are microscopy and ultrafiltration. Methods for determining the sizes of proteins and DNA molecules are ultrafiltration, gel filtration, gel electrophoresis, centrifugation, and direct calculation of molecular weight. Note that DNA is a long linear molecule and proteins are generally globular and RNA is in between, so direct comparison of sizes is complicated and the figures given are approximations.

I hope this has given you an idea of what's involved in answering the question, "What is the smallest living thing?". Mike Conrad.

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