More moonlighting

For years, I have used the hypothesis of front-loading to argue that multifunctional, moonlighting proteins would be expected to exist.  I explained the logic and provided many examples using the ribosome as a candidate of such front-loading.  In fact, as far as I know, I’m the only one to note that the gene for the ribosomal protein s5 also seems to code for a protein that is expressed in the mammalian brain (see here and here).

A fresh new study has just been published that fits seamlessly with the above essays:

In a car, the key parts are usually specialized to do a specific job; the carburetor adjusts the mixture of air to gasoline that gets injected into the engine’s cylinders, for example. But cells work differently, as a new study illustrates, with some proteins that have crucial jobs as “housekeeping proteins” also moonlighting with “part-time jobs” on the side.

As a new study in PLoS Biology shows, one such housekeeping protein turns out to have a side job in regulating the Notch signaling pathway, which all animals use for signaling between cells, and is crucial for normal development. This comes as a surprise, since that means the protein responsible has a side job that’s arguably as crucial as its main job.

So what is this housekeeping gene?  Eukaryotic translation initiation factor 3 subunit f (eIF3f):

The eIF3f protein was already known to have a crucial job as part of a larger set of several proteins that work together, known as the eIF3 complex. The eIF3 helps assemble a much larger complex of proteins essential for translation, the process of reading strands of RNA, and assembling proteins according to the RNA’s code.

So a protein, intimately associated with the ribosome in its act of translation, also turns out to have an essential function in a signaling pathway used by metazoans.

From the DM:

This basic fact about design could be exploited to partially solve our design problem. We could simply design proteins with the capability or potential to carry out multiple functions. The proteins could be designed such that one function serves uni-cellular life while another function serves a multicellular task. As long as the multiple functions are encoded by the same sequence of amino acids, selection will maintain the sequence necessary for uni-cellular life, thus indirectly preserving the multi-cellular function to be exploited when multi-cellular states appear.


The hypothesis of front-loading would predict these fifty-six examples are just the tip of the iceberg. In fact, because of their telic utility, a front-loading perspective predicts that multi-functional proteins will turn out to be commonplace.

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