Balancing selection maintains polymorphisms at neurogenetic loci in field experiments

Abstract

Most variation in behavior has a genetic basis, but the processes determining the level of diversity at behavioral loci are largely unknown for natural populations. Expression of arginine vasopressin receptor 1a (Avpr1a) and oxytocin receptor (Oxtr) in specific regions of the brain regulates diverse social and reproductive behaviors in mammals, including humans. That these genes have important fitness consequences and that natural populations contain extensive diversity at these loci implies the action of balancing selection. In Myodes glareolus, Avpr1a and Oxtr each contain a polymorphic microsatellite locus located in their 5′ regulatory region (the regulatory regionassociated microsatellite, RRAM) that likely regulates gene expression. To test the hypothesis that balancing selection maintains diversity at behavioral loci, we released artificially bred females and males with different RRAM allele lengths into field enclosures that differed in population density. The length of Avpr1a and Oxtr RRAMs was associated with reproductive success, but population density and the sex interacted to determine the optimal genotype. In general, longer Avpr1a RRAMs were more beneficial for males, and shorter RRAMs were more beneficial for females; the opposite was true for Oxtr RRAMs. Moreover, Avpr1a RRAM allele length is correlated with the reproductive success of the sexes during different phases of reproduction; for males, RRAM length correlated with the numbers of newborn offspring, but for females selection was evident on the number of weaned offspring. This report of density-dependence and sexual antagonism acting on loci within the arginine vasopressin-oxytocin pathway explains how genetic diversity at Avpr1a and Oxtr could be maintained in natural populations. Myodes glareolusM ost variation in behavior has a substantial genetic basis.Identifying loci that underpin the expression of behavior is central to our understanding of the evolution and adaptive significance of behavioral diversity (1, 2). Although many studies have found an association between genotype and behavior (2-4), few have quantified the eco-evolutionary dynamics of these genetic polymorphisms. A corollary of the diversity of behaviors exhibited in wild populations is the action of balancing selection (3, 5), a general term for mechanisms that promote fitness of alternate genotypes, including density-dependent selection (1), negative frequencydependent selection (6), heterozygote advantage (7), and sexual antagonism (8, 9). Density-and frequency-dependent selection, for example, can maintain polymorphisms at the foraging gene in laboratory populations of Drosophila melanogaster (1, 10). However, the lack of evidence for the conditions that drive balancing selection on behavioral loci in natural settings creates a challenge to behavioral genetics in understanding the dynamics of behavioral loci in real-world scenarios. Genes within the arginine vasopressin-oxytocin pathway present a classic opportunity to meet this challenge; its constituent loci have ...

Male-biased gene expression resolves sexual conflict through the evolution of sex-specific genetic architecture

“…The mechanisms by which sexual conflict manifests within the genome have been the focus of considerable recent debate (Innocenti and Morrow ; Cheng and Kirkpatrick ; Lonn et al. ). We find that the majority of sexual conflict in guppies arises from differential fitness effects related to reproduction, rather than viability.…”

“…Sexual conflict can result over reproductive fitness, where an allele increases the reproductive success of one sex at a cost to the other (Lonn et al. ). However, sexual conflict can also result when an allele has differential effects on viability, mortality or predation between males and females.…”

“…Sexual conflict can arise from several forces, and the population genetic signature varies according the type of sexual conflict (Table 1). Sexual conflict can result over reproductive fitness, where an allele increases the reproductive success of one sex at a cost to the other (Lonn et al 2017). However, sexual conflict can also result when an allele has differential effects on viability, mortality or predation between males and females.…”

Complex selection on a regulator of social cognition: Evidence of balancing selection, regulatory interactions and population differentiation in the prairie vole Avpr1a locus

“…Lonn et al. () recently found evidence of balancing selection at both oxytocin and vasopressin receptors in bank voles. Researchers in evolutionary psychology have speculated that genetic contributions to human personality might be under balancing selection (Keller & Miller, ), but initial reports have not strongly supported this prediction (Verweij et al., ).…”

Flexible mixture model approaches that accommodate footprint size variability for robust detection of balancing selection

“…In addition to overdominance (Charlesworth and Charlesworth, 2010), other processes such as sexual selection (Cho et al, 2006), periodical environmental shifts (Bergland et al, 2014), pleiotropy (Andrés, 2001;Mitchell-Olds et al, 2007), meiotic drive (Ubeda and Haig, 2004;Charlesworth and Charlesworth, 2010), and negative frequency-dependent selection (Charlesworth and Charlesworth, 2010) can also maintain diversity at underlying loci. Due to the increasing availability of population level genomic data, in which allele frequencies and genomic density of polymorphisms can be assessed in detail, there is an expanding interest in studying balancing selection and detecting its genomic footprints (e.g., Andrés et al, 2009;Leffler et al, 2013;DeGiorgio et al, 2014;Gao et al, 2015;Hunter-Zinck and Clark, 2015;Sheehan and Song, 2016;Lonn et al, 2017;Sweeney et al, 2017;Guirao-Rico et al, 2017;Voight, 2017, 2018;Bitarello et al, 2018;Ye et al, 2018;Cheng and DeGiorgio, 2019).…”