For free-living organisms, the ability to sense and respond to the outside environment is crucial for survival. Eukaryotes, such as animals and plants, often have highly complex network systems in place to monitor their surroundings and respond effectively, but bacteria have developed a remarkably simple system. It's called the 'Two Component System' because it literally relies on just two components; a sensor and a responder. The sensor picks up the signal, communicates this to the responder, which then causes the effect.

The components of the two-component signalling system. Picture (c) me.

The picture above shows this process happening. The 'communication' of the message from the sensor to the responder, as shown by the coloured arrows, is carried out by transferring phosphate molecules. The signal interacting with the sensor causes the sensor to autophosphorylate (phosphorylate itself) and then pass the phosphate molecule onto the responder to trigger the response. The letters "H" and "D" are the actual amino-acids being phosphorylated; Histadine and Aspartate.

Although Two-Component Systems (TCS) are found in all three superkingdoms of life (archaea, bacteria and eukaryotes) they are suspiciously absent from the animal kingdom. Plants have them, as do fungi and several protazoa, but they just aren't present in animals. For this reason they've been looked into as potential antibiotic targets as knocking out the Two-Component Systems of most bacteria is fatal.

Why don't animals use TCS? To answer this you have to start looking at the evolution of the system itself, because despite being nominally present in eukaryotes such as plants and fungi, TCS are used very differently. Bacteria use TCS for sensing a wide variety of signals; stress, metabolism, nutrient regulation, chemotaxis, pathogen-host interactions etc. In eukaryotes on the other hand they are used sparingly; for ethylene responses and photosensitivity in plants and osmoregulation in fungi and slime moulds.

Bacteria (especially soil bacteria which have a lot of environment to sense) can contain up to 50 TCS although many internal parasite bacteria contain a lot fewer. The maximum number found in archaea is around 20 and they are even scarer in eukaryotes with only one in bakers yeast (Saccharomyces cerevisiae - one sensor kinase and three response regulators). None have yet been found in any animal genomes, or in the protist genomes as far as I know (although it is possible recent protist research may have unearthed a few)

Comparing the TCS genes of bacteria, archaea and eukaryotes leads to the interesting conclusion that the bacterial and eukaryotic systems are far more closely related than the archaeal, and in fact are thought to be monophyletic (all evolved from a single common ancestor). In contrast, the archaeal TCS appear to be polyphyletic (several ancestors) and some archaea lack TCS entirely. It's therefore thought that TCS originated in bacteria and spread by horizontal gene transfer to both archaea and eukaryotes. As horizontal gene transfer relies on DNA moving from one species to another, no further transfer to eukaryotes could occur after they developed larger cells with a nuclear membrane. In eukaryotes very little further diversification took place, whereas the bacterial TCS diversified widely, and occasionally passed new systems back to the archaea. I've tried to show this in the diagram below:

The passage of genes for two-component-systems through the three superkingdoms of life

The diagram above attempts to show the movement of the TCS genes through the three superkingdoms of life. Red arrows show the horizontal transfer (straight arrows) and gene duplication (curved arrows) of TCS genes. No horizontal gene transfer can take place in eukaryotes after the nuclear membrane ( can do but is very, very rare) although gene duplication may still have occurred.

The eukaryotic superkingdom appears not to have contained very many of these TCS genes to start with, and the animal kingdom may just have lost the very few it possessed. This makes sense from the point of view of cellular control because while TCS are very useful in bacteria with their small genome and independent lifestyles, it's less clear how useful they are in eukaryotes as a whole. Introducing a membrane around the nucleus makes it harder for proteins to get in and bind to the DNA, and in a large complicated cell it's harder for a simple two-component system to sense what's going on. Added to which, cells inside a multicellular organism don't really need to sense what's going on, they get told what's going on by the surrounding cells and circulating hormones.

Whatever the reason though it is clear that despite this system being vital for bacteria it isn't used widely, or most likely at all, in animals. Research into this would be particularly useful against opportunistic pathogens which tend to have a large selection of two-component systems to allow them to adapt to different lifestyles depending on the conditions of their immediate environment.


Kristin K. Koretke , Andrei N. Lupas , Patrick V. Warren , Martin Rosenberg , and James R. Brown (2000). Evolution of Two-Component Signal Transduction Mol Biol Evol, 17, 1956-1970

Wolanin PM, Thomason PA, & Stock JB (2002). Histidine protein kinases: key signal transducers outside the animal kingdom. Genome biology, 3 (10) PMID: 12372152