A Single-Protein Model of Music Perception

3 September, 2008
An attempt to define a minimal biological model of music perception, involving just one human-specific variant protein expressed on the afferent synapses of one particular group of cortical neurons.


The motivation for this model is to provide a starting point for the search for the "musical genes". I want to know what is the simplest mechanism which can result in the perception of music.

Single-Protein versus Multi-Protein or Zero-Protein

The model to be described here is "single-protein" in the sense that:

It is quite possible that one protein is not enough, and that the perception of music involves at least two proteins. However, from an evolutionary point of view, there must have been one protein which was first to evolve in the direction of human musical perception.

In general I think it is useful to consider the simplest possible model that might explain something, just for the sake of exploring how simple the explanation could be, and perhaps to discover by some means that some slightly higher level of complexity is indeed required.

An even smaller number than one is zero, and it is possible to imagine a zero-protein model of music perception, where music perception is entirely determined by non-proteing encoding genes which, for example, determine the expression of existing proteins in a manner which controls the connectivity between different types of neurons resulting in the perception of music.

The Model

The model I am presenting assumes the following informational "circuit":

This particular model implies certain constraints on the participants:

Candidates for M-precursor, i.e. for types of protein that protein M could be a variant of, include:

Although the model above specifies action on excitatory synapses, it is also possible that protein M acts on inhibitory synapses, in which case it would have to act in the opposite direction, i.e. contrast between relative concentrations of A and B would result in a reduction of inhibitory response in the synapse.

Is there a "musical neurotransmitter"?

The single-protein model is in effect a zero-neurotransmitter model. This is because although protein M is acted on by molecules A and B, it responds only to their relative concentrations at one particular location, and there is no sense in which the relevant information can be transmitted from further away.

A Two-Protein Model

If we consider the possibility of some kind of musical neurotransmitter, then the model becomes a two-protein model, i.e. one protein M1 to release the neurotransmitter, and one protein M2 to receive it.

In this extended model, protein M1 is the one that responds to the relative concentrations of molecules A and B, and consequentially increases the amount of the musical neurotransmitter MN in the extra-cellular medium. Protein M2 is situated on the afferent synapses of the amygdala-projecting cortical neurons, and it contains a domain which responds to the presence of MN in a manner which modulates its normal function.

In principle the transmission of MN might occur over an arbitrarily large distance across the brain. However in practice the transmission may be limited to a relatively short distance, for at least two reasons.

The first reason is that transmission of MN is entirely by diffusion, and there is still a requirement for the relevant information to be transmitted within a required timescale of seconds at the most.

A second reason is that at least one of the proteins M1 or M2 is likely to be more "music-specific" than the other. Again, considering the evolutionary origin of music, one of the two proteins had to evolve first, as a variant of some other protein, i.e. either M1-precursor or M2-precursor.

One possible scenario is the following:

Possible Types of Protein Variant

Both the one-protein and two-protein models require the evolution some human-specific variant of a pre-existing brain protein.

Various forms of protein variant are known, including:

It is a surprising fact about the human genome that very few human-specific brain-expressed protein genes have been discovered.

The human genome has been fully sequenced, and protein genes can usually be directly identified according to:

It follows that most obvious duplicate protein brain genes would already have been found, unless they are very cleverly "hiding" from scientific view.

However alternate splicing is one form of duplication which is less obviously detectable, involving as it does duplication of a gene in its current location, and this remains a possibility for discovering as-yet undiscovered human-specific brain genes.

One example of a human-specific variant protein due to alternative splicing is Neuropsin II (the nature and expression of this variant protein rule it out as a possible candidate for any of the M proteins in the models just described).

One apparent example of a fully duplicated human-specific brain-expressed gene is SIGLEC11 (and see also the OMIM page), but this seems to be more relevant to immunity than to information processing, as it is expressed on the microglia which are part of the immune system.

Zero-Protein Models

Various forms of human-specific non-protein "genes" have been discovered. For example the paper Accelerated Evolution of Conserved Noncoding Sequences in Humans describes the discovery of human-specific promoter sequences which promote the expression of neural-adhesion proteins. Such genes are likely to be involved in the human-specific patterns of wiring in the brain, and they demonstrate how humans can have evolved in very human-specific ways without evolving any new actual proteins.

Unfortunately this kind of model does not help to explain music, at least not within the framework of the super-stimulus theory, which requires the "observation" of patterns of neural activity. This type of observation is most directly achieved by "observing" concentrations of activity-related molecules, which is the sort of thing that only a specialised protein can do.

One could perhaps imagine the evolution of some novel neural connectivity patterns which would support the observation of constant activity patterns, however one would expect this to produce some anatomically obvious difference between human and non-human brains, especially in the auditory cortex, and no such difference has ever been observed, to the best of my knowledge.