Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene

Abstract

The molecular mechanisms underlying the evolution of complex behaviour are poorly understood. The mammalian genus Microtus provides an excellent model for investigating the evolution of social behaviour. Prairie voles (Microtus ochrogaster) exhibit a monogamous social structure in nature, whereas closely related meadow voles (Microtus pennsylvanicus) are solitary and polygamous1. In male prairie voles, both vasopressin and dopamine act in the ventral forebrain to regulate selective affiliation between adult mates, known as pair bond formation, as assessed by partner preference in the laboratory2,3,4. The vasopressin V1a receptor (V1aR) is expressed at higher levels in the ventral forebrain of monogamous than in promiscuous vole species5, whereas dopamine receptor distribution is relatively conserved between species. Here we substantially increase partner preference formation in the socially promiscuous meadow vole by using viral vector V1aR gene transfer into the ventral forebrain. We show that a change in the expression of a single gene in the larger context of pre-existing genetic and neural circuits can profoundly alter social behaviour, providing a potential molecular mechanism for the rapid evolution of complex social behaviour.

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Figure 1: Comparison of brain neurochemistry and behaviour in prairie and meadow voles.
Figure 2: V1aR autoradiography at the level of the ventral pallidum.
Figure 3: Partner preference test.
Figure 4: Partner preference test after eticlopride pretreatment.

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Acknowledgements

We thank C. A. Sharer for contributing to the initial viral vector work, L. Miller for assistance with meadow vole breeding, and A. Z. Murphy and E. A. D. Hammock for their critical readings of the manuscript. Funding for this work was provided by grants from the NIH to M.M.L., Z.X.W., L.J.Y. and the Yerkes Center, and by a NSF STC grant to the Center for Behavioral Neuroscience.Authors' contributions M.M.L. performed the experiments and wrote the manuscript. Z.X.W. provided the animals and behavioural testing equipment for the pilot studies, the D2 autoradiography protocol and scientific input. D.E.O. assisted with the paternal behaviour testing. X.H.R. and E.F.T. generated the viral vectors. L.J.Y. conceived the idea and co-wrote the manuscript.

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Correspondence to Larry J. Young.

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Lim, M., Wang, Z., Olazábal, D. et al. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429, 754–757 (2004). https://doi.org/10.1038/nature02539

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