Musical Genomics and the Musical Astrocyte Theory

25 October, 2006
Combining recent advances in identifying human accelerated regions in the human genome with the possibility that music perception involves non-neuronal circuitry (i.e. glial cells such as astrocytes), it may be sooner rather than later that a strong candidate for a musical gene can be identified.

Musical Astrocytes

In a previous article, I considered the possibility that the "musicality-detecting brain cells" required by my super-stimulus theory of music might actually be glial cells rather than neurons. A brief summary of the rationale for this hypothesis is as follows:

I have been giving this musical astrocyte theory more thought, and I have been wondering whether there may be some indirect way to verify this theory. (A direct way would be to physically inspect the inner parts a subject's brain while they enjoy listening to music, which can't be done on a person because it is way too dangerous, and can't be done on a non-human animal because animals do not, as far as anyone knows, appreciate the musicality of music).

One possible alternative approach is comparative genomics. Even just assuming that music is uniquely human and that it serves some biological purpose for which it has been selected for, we can deduce that there will exist regions in the human genome which "encode" for music, and the genes or genetic variation in these regions will be unique to humans, and different even when compared to the genomes of our closes relatives (the chimpanzees and other apes). Neither of these assumptions can be made with any degree of certainty, but the strength of the human desire for music does argue in favour of some there being a musical instinct, and non-human animals show little sign of behaviour determined by any similar kind of instinct..

Human "Accelerated Regions"

Human accelerated regions (or HARs) are regions of the human genome have undergone very rapid evolution only in the human lineage, and are relatively conserved in other mammals, including even chimpanzees. Motivated by the expected benefits of such comparisons, a project to sequence the chimpanzee genome was started, and has recently been completed.

Already studies which compare human, chimpanzee and other mammalian genomes are being published. Katherine Pollard et al have published two papers describing their research into human accelerated evolution: Forces Shaping the Fastest Evolving Regions in the Human Genome (in PLOS Biology) An RNA gene expressed during cortical development evolved rapidly in humans (in Nature).

The first of these two papers describes a list of 202 HAR's identified by two statistical criteria - , according to a maximum p value calculated from a likelihood ratio test (LRT) of 0.1, which as I understand it, means that a value with a particular p value has that probability of being random variation, and not caused by actual accelerated evolution – so if all the 202 HAR's had a p-value of 0.1, then maybe 20 would be random variations, although the real number will be less than 20 since 0.1 is the maximum p-value. Also some of the identified HAR's have a much lower p-value for a different statistic.

The second paper describes analysis of the first of the identified HAR's, called HAR1. This turns out to be a region of overlap between two different RNA encoding genes, strongly conserved in most mammals (of those studied) but varying significantly in humans. (Unfortunately the Nature paper is not freely available online, but some web pages describing the work can be found here, here, here and here.)

Slightly older work involving human accelerated evolution is the identification of the FOXP2 protein as being subject to accelerated evolution in the human lineage, as described in Accelerated Protein Evolution and Origins of Human-Specific Features: FOXP2 as an Example (Zhang et al, Genetics, Vol. 162, 1825-1835, December 2002). (Note that the FOXP2 gene is not on the previously mentioned list of 202 HAR's, so it appears that multiple methods are going to be required to identify all the HAR's that are in the human genome.)

The FOXP2 gene is particularly interesting because it appears related to the development of speech in the human species. This has a bearing on music: I've already mentioned that music is a candidate for accelerated evolution just on the assumption that it is a unique human capacity which relates to some (possibly unknown) biological function, but given that music appears to be related in some way to speech, if there are regions of accelerated evolution related to speech, then we have even more reason to expect that there might be regions of accelerated evolution related to music.

Application to Musical Astrocytes

In the fullness of time, all human genes will be identified with the human characteristics that they encode for and which have been selected for accordingly by natural selection. And no doubt "musical genes" will be discovered which account for our response to music.

However, if music perception involves an unusual non-neuronal circuit, i.e. one involving astrocytes, then this discovery might happen sooner rather than later. In many cases it can be determined where a particular gene is expressed, without necessarily knowing what the purpose or consequence of such expression is (for example see the Allen Brain Atlas which documents the locations of genes expressed in the mouse brain). One would expect that most human accelerated evolution of brain-related genes would specifically relate to neurons. So if HAR's were found which were genes expressed in some other type of brain cell, such as astrocytes, then this could be a strong clue that such a gene relates to music perception.

If a particular candidate for a musical gene could be found, this may make it easier to perform other genetic studies relating to music, for example sequencing allelic variation in a large sample of people and comparing it to their musical talents and preferences.

At the moment, as far as I know, no HAR's have been identified which specifically relate to astrocytes. But of the 202 HAR's identified by Pollard et al, only the very first has been thoroughly studied so far. So it's early days yet.

Further Reading on Genomics

Further Reading on Astrocytes and Neuron/Astrocyte Interactions