Gene regulatory changes underlie developmental plasticity in respiration and aerobic performance in highland deer mice

Phenotypic plasticity can play an important role in the ability of animals to tolerate environmental stress, but the nature and magnitude of plastic responses are often specific to the developmental timing of exposure. Here, we examine changes in gene expression in the diaphragm of highland deer mice (Peromyscus maniculatus) in response to hypoxia exposure at different stages of development. In highland deer mice, developmental plasticity in diaphragm function may mediate changes in several respiratory traits that influence aerobic metabolism and performance under hypoxia. We generated RNAseq data from diaphragm tissue of adult deer mice exposed to (1) life-long hypoxia (before conception to adulthood), (2) post-natal hypoxia (birth to adulthood), (3) adult hypoxia (6–8 weeks only during adulthood) or (4) normoxia. We found five suites of co-regulated genes that are differentially expressed in response to hypoxia, but the patterns of differential expression depend on the developmental timing of exposure. We also identified four transcriptional modules that are associated with important respiratory traits. Many of the genes in these transcriptional modules bear signatures of altitude-related selection, providing an indirect line of evidence that observed changes in gene expression may be adaptive in hypoxic environments. Our results demonstrate the importance of developmental stage in determining the phenotypic response to environmental stressors. Includes supplementary materials

Mapping evolutionary process: a multi-taxa approach to conservation prioritization

Human-induced land use changes are causing extensive habitat fragmentation. As a result, many species are not able to shift their ranges in response to climate change and will likely need to adapt in situ to changing climate conditions. Consequently, a prudent strategy to maintain the ability of populations to adapt is to focus conservation efforts on areas where levels of intraspecific variation are high. By doing so, the potential for an evolutionary response to environmental change is maximized. Here, we use modeling approaches in conjunction with environmental variables to model species distributions and patterns of genetic and morphological variation in seven Ecuadorian amphibian, bird, and mammal species. We then used reserve selection software to prioritize areas for conservation based on intraspecific variation or species-level diversity. Reserves selected using species richness and complementarity showed little overlap with those based on genetic and morphological variation. Priority areas for intraspecific variation were mainly located along the slopes of the Andes and were largely concordant among species, but were not well represented in existing reserves. Our results imply that in order to maximize representation of intraspecific variation in reserves, genetic and morphological variation should be included in conservation prioritization

Genome sequencing highlights the dynamic early history of dogs

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11-16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary

Genome Sequencing Highlights Genes Under Selection and the Dynamic Early History of Dogs

Abstract To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we analyzed novel high-quality genome sequences of three gray wolves, one from each of three putative centers of dog domestication, two ancient dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. We find dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow, which confounds previous inferences of dog origins. In dogs, the domestication bottleneck was severe involving a 17 to 49-fold reduction in population size, a much stronger bottleneck than estimated previously from less intensive sequencing efforts. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was far larger than represented by modern wolf populations. Conditional on mutation rate, we narrow the plausible range for the date of initial dog domestication to an interval from 11 to 16 thousand years ago. This period predates the rise of agriculture and, along with new evidence from variation in amylase copy number, implies that the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that surprisingly, none of the extant wolf lineages from putative domestication centers are more closely related to dogs, and the sampled wolves instead form a sister monophyletic clade. This result, in combination with our finding of dogwolf admixture during the process of domestication, suggests a re-evaluation of past hypotheses of dog origin is necessary. Finally, we also detect signatures of selection, including evidence for selection on genes implicated in morphology, metabolism, and neural development. Uniquely, we find support for selective sweeps at regulatory sites suggesting gene regulatory changes played a critical role in dog domestication

Physiological and genomic evidence that selection on the transcription factor Epas1 has altered cardiovascular function in highaltitude deer mice

Evolutionary adaptation to extreme environments often requires coordinated changes in multiple intersecting physiological pathways, but how such multi-trait adaptation occurs remains unresolved. Transcription factors, which regulate the expression of many genes and can simultaneously alter multiple phenotypes, may be common targets of selection if the benefits of induced changes outweigh the costs of negative pleiotropic effects. We combined complimentary population genetic analyses and physiological experiments in North American deer mice (Peromyscus maniculatus) to examine links between genetic variation in transcription factors that coordinate physiological responses to hypoxia (hypoxia-inducible factors, HIFs) and multiple physiological traits that potentially contribute to high-altitude adaptation. First, we sequenced the exomes of 100 mice sampled from different elevations and discovered that several SNPs in the gene Epas1, which encodes the oxygen sensitive subunit of HIF-2α, exhibited extreme allele frequency differences between highland and lowland populations. Broader geographic sampling confirmed that Epas1 genotype varied predictably with altitude throughout the western US. We then discovered that Epas1 genotype influences heart rate in hypoxia, and the transcriptomic responses to hypoxia (including HIF targets and genes involved in catecholamine signaling) in the heart and adrenal gland. Finally, we used a demographically-informed selection scan to show that Epas1 variants have experienced a history of spatially varying selection, suggesting that differences in cardiovascular function and gene regulation contribute to high-altitude adaptation. Our results suggest a mechanism by which Epas1 may aid long-term survival of high-altitude deer mice and provide general insights into the role that highly pleiotropic transcription factors may play in the process of environmental adaptation

Data from: Genetic subdivision and candidate genes under selection in North American gray wolves

Previous genetic studies of the highly mobile gray wolf (Canis lupus) found population structure that coincides with habitat and phenotype differences. We hypothesized that these ecologically distinct populations (ecotypes) should exhibit signatures of selection in genes related to morphology, coat color, and metabolism. To test these predictions, we quantified population structure related to habitat using a genotyping array to assess variation in 42,036 SNPs in 111 North American gray wolves. Using these SNP data and individual-level measurements of 12 environmental variables, we identified six ecotypes: West Forest, Boreal Forest, Arctic, High Arctic, British Columbia, and Atlantic Forest. Next, we explored signals of selection across these wolf ecotypes through the use of three complementary methods to detect selection: FST/haplotype homozygosity bivariate percentile, BayeScan, and environmentally correlated directional selection with Bayenv. Across all methods, we found consistent signals of selection on genes related to morphology, coat coloration, metabolism, as predicted, as well as vision and hearing. In several high-ranking candidate genes, including LEPR, TYR, and SLC14A2, we found variation in allele frequencies that follow environmental changes in temperature and precipitation, a result that is consistent with local adaptation rather than genetic drift. Our findings show that local adaptation can occur despite gene flow in a highly mobile species and can be detected through a moderately dense genomic scan. These patterns of local adaptation revealed by SNP genotyping likely reflect high fidelity to natal habitats of dispersing wolves, strong ecological divergence among habitats, and moderate levels of linkage in the wolf genome

SweeD_Report.Pop_2_BorealForest_Neutral_10000_chrAll

Sweed Output file for Boreal Forest Wolves & neutral sites. Columns are chromosome, position, likelihood, and alpha. See SweeD details at http://sco.h-its.org/exelixis/web/software/sweed

Data from: Targeted capture and resequencing of 1040 genes reveal environmentally driven functional variation in gray wolves

In an era of ever-increasing amounts of whole genome sequence data for individuals and populations, the utility of traditional single nucleotide polymorphisms (SNPs) array-based genome scans is uncertain. We previously performed a SNP array-based genome scan to identify candidate genes under selection in six distinct gray wolf (Canis lupus) ecotypes. Using this information, we designed a targeted capture array for 1040 genes, including all exons and flanking regions, as well as 5000 1 kb non-genic neutral regions and resequenced these regions in 107 wolves. Selection tests revealed striking patterns of variation within candidate genes relative to non-candidate regions and identified potentially functional variants related to local adaptation. We found 27% and 47% of candidate genes from the previous SNP array study had functional changes that were outliers in SweeD and Bayenv analyses, respectively. This result verifies the use of genome wide SNP surveys to tag genes that contain functional variants between populations. We highlight non-synonymous variants in APOB, LIPG, and USH2A that occur in functional domains of these proteins, and that demonstrate high correlation with precipitation seasonality and vegetation. We find Arctic and High Arctic wolf ecotypes have higher numbers of genes under selection, which highlight their conservation value and heightened threat due to climate change. This study demonstrates that combining genome wide genotyping arrays with large scale resequencing and environmental data provides a powerful approach to discern candidate functional variants in natural populations