Population genomics applications for conservation: the case of the tropical dry forest dweller Peromyscus melanophrys

Recent advances in genomic sequencing have opened new horizons in the study of population genetics and evolution in non-model organisms. However, very few population genomic studies have been performed on wild mammals to understand how the landscape affects the genetic structure of populations, useful information for the conservation of biodiversity. Here, we applied a genomic approach to evaluate the relationship between habitat features and genetic patterns at spatial and temporal scales in an endangered ecosystem, the Tropical Dry Forest (TDF). We studied populations of the Plateau deer mouse Peromyscus melanophrys to analyse its genomic diversity and structure in a TDF protected area in the Huautla Mountain Range (HMR), Mexico based on 8,209 SNPs obtained through Genotyping-by-Sequencing. At a spatial scale, we found a significant signature of isolation-by-distance, few significant differences in genetic diversity indices among study sites, and no significant differences between habitats with different levels of human perturbation. At a temporal scale, while genetic diversity levels fluctuated significantly over time, neither seasonality nor disturbance levels had a significant effect. Also, outlier analysis revealed loci potentially under selection. Our results suggest that the population genetics of P. melanophrys may be little impacted by anthropogenic disturbances, or by natural spatial and temporal habitat heterogeneity in our study area. The genome-wide approach adopted here provides data of value for conservation planning, and a baseline to be used as a reference for future studies on the effects of habitat fragmentation and seasonality in the HMR and in TDF

Dissecting Epigenetic Silencing Complexity in the Mouse Lung Cancer Suppressor Gene Cadm1

Disease-oriented functional analysis of epigenetic factors and their regulatory mechanisms in aberrant silencing is a prerequisite for better diagnostics and therapy. Yet, the precise mechanisms are still unclear and complex, involving the interplay of several effectors including nucleosome positioning, DNA methylation, histone variants and histone modifications. We investigated the epigenetic silencing complexity in the tumor suppressor gene Cadm1 in mouse lung cancer progenitor cell lines, exhibiting promoter hypermethylation associated with transcriptional repression, but mostly unresponsive to demethylating drug treatments. After predicting nucleosome positions and transcription factor binding sites along the Cadm1 promoter, we carried out single-molecule mapping with DNA methyltransferase M.SssI, which revealed in silent promoters high nucleosome occupancy and occlusion of transcription factor binding sites. Furthermore, M.SssI maps of promoters varied within and among the different lung cancer cell lines. Chromatin analysis with micrococcal nuclease also indicated variations in nucleosome positioning to have implications in the binding of transcription factors near nucleosome borders. Chromatin immunoprecipitation showed that histone variants (H2A.Z and H3.3), and opposing histone modification marks (H3K4me3 and H3K27me3) all colocalized in the same nucleosome positions that is reminiscent of epigenetic plasticity in embryonic stem cells. Altogether, epigenetic silencing complexity in the promoter region of Cadm1 is not only defined by DNA hypermethylation, but high nucleosome occupancy, altered nucleosome positioning, and ‘bivalent’ histone modifications, also likely contributed in the transcriptional repression of this gene in the lung cancer cells. Our results will help define therapeutic intervention strategies using epigenetic drugs in lung cancer

Is Promiscuity Associated with Enhanced Selection on MHC-DQα in Mice (genus Peromyscus)?

Reproductive behavior may play an important role in shaping selection on Major Histocompatibility Complex (MHC) genes. For example, the number of sexual partners that an individual has may affect exposure to sexually transmitted pathogens, with more partners leading to greater exposure and, hence, potentially greater selection for variation at MHC loci. To explore this hypothesis, we examined the strength of selection on exon 2 of the MHC-DQα locus in two species of Peromyscus. While the California mouse (P. californicus) is characterized by lifetime social and genetic monogamy, the deer mouse (P. maniculatus) is socially and genetically promiscuous; consistent with these differences in mating behavior, the diversity of bacteria present within the reproductive tracts of females is significantly greater for P. maniculatus. To test the prediction that more reproductive partners and exposure to a greater range of sexually transmitted pathogens are associated with enhanced diversifying selection on genes responsible for immune function, we compared patterns and levels of diversity at the Class II MHC-DQα locus in sympatric populations of P. maniculatus and P. californicus. Using likelihood based analyses, we show that selection is enhanced in the promiscuous P. maniculatus. This study is the first to compare the strength of selection in wild sympatric rodents with known differences in pathogen milieu