Genetic Differentiation of Hypothalamus Parentally Biased Transcripts in Populations of the House Mouse Implicate the Prader–Willi Syndrome Imprinted Region as a Possible Source of Behavioral Divergence

Abstract

Parentally biased expression of transcripts (genomic imprinting) in adult tissues, including the brain, can influence and possibly drive the evolution of behavioral traits. We have previously found that paternally determined cues are involved in population-specific mate choice decisions between two populations of the Western house mouse (Mus musculus domesticus). Here, we ask whether this could be mediated by genomically imprinted transcripts that are subject to fast differentiation between these populations. We focus on three organs that are of special relevance for mate choice and behavior: The vomeronasal organ (VNO), the hypothalamus, and the liver. To first identify candidate transcripts at a genome-wide scale, we used reciprocal crosses between M. m. domesticus and M. m. musculus inbred strains and RNA sequencing of the respective tissues. Using a false discovery cutoff derived from mock reciprocal cross comparisons, we find a total of 66 imprinted transcripts, 13 of which have previously not been described as imprinted. The largest number of imprinted transcripts were found in the hypothalamus; fewer were found in the VNO, and the least were found in the liver. To assess molecular differentiation and imprinting in the wild-derived M. m. domesticus populations, we sequenced the RNA of the hypothalamus from individuals of these populations. This confirmed the presence of the above identified transcripts also in wild populations and allowed us to search for those that show a high genetic differentiation between these populations. Our results identify the Ube3a–Snrpn imprinted region on chromosome 7 as a region that encompasses the largest number of previously not described transcripts with paternal expression bias, several of which are at the same time highly differentiated. For four of these, we confirmed their imprinting status via single nucleotide polymorphism-specific pyrosequencing assays with RNA from reciprocal crosses. In addition, we find the paternally expressed Peg13 transcript within the Trappc9 gene region on chromosome 15 to be highly differentiated. Interestingly, both regions have been implicated in Prader–Willi nervous system disorder phenotypes in humans. We suggest that these genomically imprinted regions are candidates for influencing the population-specific mate-choice in mice.

The imprinted lncRNA Peg13 regulates sexual preference and the gender-specific brain transcriptome in mice

“…In a previous study on assortative mating preferences between wild-type populations of M. m. domesticus mice, we had found a paternal influence on mate choice patterns in semi-natural environments (9). In a subsequent analysis we identified two paternally imprinted loci that evolve particularly fast between the mouse populations as possible candidates to influence this mate choice pattern (10). One of them is Peg13, a single exon non-coding RNA gene on mouse chromosome 15, originally identified as a locus with differential methylation of the paternal and maternal chromosomes (11).…”

“…One of them is Peg13, a single exon non-coding RNA gene on mouse chromosome 15, originally identified as a locus with differential methylation of the paternal and maternal chromosomes (11). Peg13 is expressed in many organs from the paternal allele only, but with the highest expression throughout the brain, including olfactory bulbs and vomeronasal organ (10,12). It is located within an intron of Trappc9, a gene that shows a maternal expression bias (i.e.…”

Natural copy number differences of tandemly repeated small nucleolar RNAs in the Prader-Willi syndrome genomic region regulate individual behavioral responses in mammals

“…Ube3a is expressed from the maternal chromosome, the others from the paternal one. Note that the transcript structures are actually more complex and not yet fully resolved (Lorenc et al 2014;Cavaille 2017). The tandem clusters coding for the SNORD115 and SNORD116 snoRNAs are depicted by smaller block arrows (not drawn to size).…”

Validating standardised personality tests under semi‐natural conditions in wild house mice (Mus musculus domesticus)

“…These populations belong to the same subspecies and can still produce fertile offspring but have adapted to different environments for approximately 3,000 years (Cucchi, Vigne, & Auffray, 2005). During this separation, they have developed a number of genetic (Byrk, Somel, Lorenc, & Teschke, 2013;Ihle, Ravaoarimanana, Thomas, & Tautz, 2006;Lorenc, Linnenbrink, Montero, Schilhabel, & Tautz, 2014;Staubach et al, 2012), morphological (Skrabar, Turner, Pallares, Harr, & Tautz, 2018) and behavioural adaptations (Linnenbrink & von Merten, 2017;von Merten, Hoier, Pfeifle, & Tautz, 2014;Montero, Teschke, & Tautz, 2013). By using two populations, we wanted to test whether potential relationships between standardised behavioural measurements and behaviours shown under semi-natural conditions are inherent to different populations of the same species or are population-specific.…”