Microsatellite mutation and brain variation

Elizabeth Hammock and Larry Young (2005) report in Science that variation in behavioral traits among different species of voles is partly controlled by variation in microsatellite loci linked to neuroactive genes.

Why voles? Here's why:

Rodents of the genus Microtus (voles) show dramatic species differences in social structure (8). Prairie voles form lifelong attachments with a mate, are biparental, and show high levels of social interest (9). In contrast, the closely related montane vole does not pair bond, the males do not contribute to parental care, and they appear socially indifferent (10). Species differences in the pattern of vasopressin 1a receptor (V1aR) expression in the brains of these species contribute to the species differences in social structure (11-13). The species-specific patterns of V1aR expression appear to be regulated by differences in a microsatellite in the 5' regulatory region of the gene encoding V1aR (avpr1a). This microsatellite is highly expanded in prosocial prairie and pine voles, consisting of several repeat blocks interspersed with nonrepetitive sequences (Fig. 1, A and B), compared with a very short version in the asocial montane and meadow voles (Hammock and Young 2005:1630, citations in original).

The theme here is that length polymorphisms in the regulatory regions of genes may have important impacts on gene expression. There are likely many genes related to behavioral variation. These include those coding for neurotransmitters and hormones, as well as genes related to the development of neural and brain structure. But most neurotransmitters and hormones are highly conserved molecules in vertebrates -- their gene sequences and consequent gene products have relatively little functional variation. The way that these molecules affect behavior is primarily modulated by the regulation of the genes. This makes mechanisms like microsatellite length polymorphisms potentially very important.

The authors hypothesize that the continuous variation of microsatellite length within a population should predict a within-species relation of microsatellite length and behavioral variation. They find that such a relation does in fact exist, and that it explains a substantial degree of the variation in social behavior of males within the prairie voles they examined. In their example, the long-allele males were quicker to approach novel oders, engaged in social interactions more readily, and generally were more inquisitive about social cues than short-allele males. In contrast, there was no difference when considering non-social odors or social situations. In this example, the mechanism was the greater presence of vasopressin 1a receptor in the olfactory bulbs of individuals with long microsatellite alleles. This appears to be a primary reason for differences in social behavior among prairie voles, and between the species of prairie voles and pine voles.

The authors further speculate that such variation may be important in regulating social behavior in hominoids:

We theorize that microsatellites in the regulatory regions of the avpr1a gene confer this locus with high levels of evolvability, which in itself may be a target of selection (32). Interestingly, four polymorphic microsatellites surround the human avpr1a gene (33). Two independent reports have indicated modest association of microsatellite alleles at the -3625 bp locus with autism (34, 35), which is a disease of profound social deficit. Considering that variation at this locus may have important implications for our own species-typical social behavior, we compared the publicly available avpr1a gene sequences of chimpanzees [Pan troglodytes (36)] and humans (37) and found that 360 bp in and around this microsatellite locus was deleted in chimpanzees, although the flanking regions were >96% conserved. In contrast, the same locus in the avpr1a gene in the bonobo (Pan paniscus), which is known for its socio-sexual reciprocity and bonding (38), has high homology with the human microsatellite (Fig. 5). Perhaps in primate species, as in vole species, both inter- and intraspecific variation in regulatory microsatellites of the avpr1a gene can give rise to behavioral variation via altered regulation of the distribution of this gene product across individuals (Hammock and Young 2005:1634, citations in original).

Very interesting. Generally, we do not know which forces cause species to alter their social systems. What causes a primate species with male philopatry and female transfer to evolve to a system where both sexes transfer? Is this an easy change to make, or is it difficult? Does the possibility of flexibility in social system occur within most primate species? Are species held in place by inertia, through their preexisting pattern of interactions, at any time ready for a relatively rapid transition to another pattern?

If there are genetic reasons for the persistence of a social system, our knowledge of it would help to answer these questions. If microsatellite variation does help to fix the regulation of neuroactive genes into adaptive configurations, then a species might be considered to be near an adaptive peak from which it might be difficult to escape. If so, then it is possible that not just any kind of environmental or selective change could result in a species changing its adaptation. Instead, special circumstances might attend shifts in social systems; privileging some populations within a species, or some (presumably more flexible) species at the expense of others. Thus, some species might harbor genes associated with easier shifts in social behavior, giving them the ability to form new kinds of social groups in response to environmental challenges or opportunities.

Of course, this is just speculation, but it shows the kinds of avenues that genetics may provide into the understanding of social variation in primates -- especially the constraints on the evolution of social changes.

References:

Hammock EAD and Young LJ. 2005. Microsatellite Instability Generates Diversity in Brain and Sociobehavioral Traits. Science 308:1630-1634. Science online