Concordant association of lipid gene variation with a combined HDL/LDL-cholesterol phenotype in two European populations

OBJECTIVE: SNP/phenotype associations are difficult to validate. This comparative study demonstrates significant contribution of candidate genes to the variation of a complex cholesterol phenotype, measured in two general populations by a gene-based approach. METHODS: Independent samples of normolipidemic subjects from two Caucasian populations (371 Swiss and 157 Germans) were selected for a case-control-study (high LDL/low HDL versus low LDL/high HDL) with SNP genotypes as independent factors. We examined locus-specific common SNPs that densely cover the genomic regions of 10 lipid genes. RESULTS: Genotype effects were concordant in both ethnic samples, showing that APOE, ABCA1, CETP, and to a lesser degree LDLR, LIPC, and PLTP explained a substantial part of the genetic variation, whereas LPL was associated in only one sample. APOA1, LCAT, and SRB1 exerted no measurable influence. CONCLUSION: This comparison showed that sets of common SNPs representing candidate regions reproducibly validate significant linkage disequilibrium association with a complex metabolic trait.     

Seascape genomics provides evidence for thermal adaptation and current‐mediated population structure in American lobster (Homarus americanus)

Investigating how environmental features shape the genetic structure of populations is crucial for understanding how they are potentially adapted to their habitats, as well as for sound management. In this study, we assessed the relative importance of spatial distribution, ocean currents and sea surface temperature (SST) on patterns of putatively neutral and adaptive genetic variation among American lobster from 19 locations using population differentiation (PD) approaches combined with environmental association (EA) analyses. First, PD approaches (using bayescan , arlequin and outflank ) found 28 outlier SNPs putatively under divergent selection and 9770 neutral SNPs in common. Redundancy analysis revealed that spatial distribution, ocean current‐mediated larval connectivity and SST explained 31.7% of the neutral genetic differentiation, with ocean currents driving the majority of this relationship (21.0%). After removing the influence of spatial distribution, no SST were significant for putatively neutral genetic variation whereas minimum annual SST still had a significant impact and explained 8.1% of the putatively adaptive genetic variation. Second, EA analyses (using Pearson correlation tests, bayescenv and lfmm ) jointly identified seven SNPs as candidates for thermal adaptation. Covariation at these SNPs was assessed with a spatial multivariate analysis that highlighted a significant temperature association, after accounting for the influence of spatial distribution. Among the 505 candidate SNPs detected by at least one of the three approaches, we discovered three polymorphisms located in genes previously shown to play a role in thermal adaptation. Our results have implications for the management of the American lobster and provide a foundation on which to predict how this species will cope with climate change.     

A Novel Candidate Region for Genetic Adaptation to High Altitude in Andean Populations

Humans living at high altitude (≥2,500 meters above sea level) have acquired unique abilities to survive the associated extreme environmental conditions, including hypoxia, cold temperature, limited food availability and high levels of free radicals and oxidants. Long-term inhabitants of the most elevated regions of the world have undergone extensive physiological and/or genetic changes, particularly in the regulation of respiration and circulation, when compared to lowland populations. Genome scans have identified candidate genes involved in altitude adaption in the Tibetan Plateau and the Ethiopian highlands, in contrast to populations from the Andes, which have not been as intensively investigated. In the present study, we focused on three indigenous populations from Bolivia: two groups of Andean natives, Aymara and Quechua, and the low-altitude control group of Guarani from the Gran Chaco lowlands. Using pooled samples, we identified a number of SNPs exhibiting large allele frequency differences over 900,000 genotyped SNPs. A region in chromosome 10 (within the cytogenetic bands q22.3 and q23.1) was significantly differentiated between highland and lowland groups. We resequenced ~1.5 Mb surrounding the candidate region and identified strong signals of positive selection in the highland populations. A composite of multiple signals like test localized the signal to FAM213A and a related enhancer; the product of this gene acts as an antioxidant to lower oxidative stress and may help to maintain bone mass. The results suggest that positive selection on the enhancer might increase the expression of this antioxidant, and thereby prevent oxidative damage. In addition, the most significant signal in a relative extended haplotype homozygosity analysis was localized to the SFTPD gene, which encodes a surfactant pulmonary-associated protein involved in normal respiration and innate host defense. Our study thus identifies two novel candidate genes and associated pathways that may be involved in high-altitude adaptation in Andean populations.     

Clinal variation in phyB2, a candidate gene for day-length-induced growth cessation and bud set, across a latitudinal gradient in European aspen (Populus tremula)

The initiation of growth cessation and dormancy represents a critical ecological and evolutionary trade-off between survival and growth in most forest trees. The most important environmental cue regulating the initiation of dormancy is a shortening of the photoperiod and phytochrome genes have been implicated in short-day-induced bud set and growth cessation in Populus. We characterized patterns of DNA sequence variation at the putative candidate gene phyB2 in 4 populations of European aspen (Populus tremula) and scored single-nucleotide polymorphisms in an additional 12 populations collected along a latitudinal gradient in Sweden. We also measured bud set from a subset of these trees in a growth chamber experiment. Buds set showed significant clinal variation with latitude, explaining approximately 90% of the population variation in bud set. A sliding-window scan of phyB2 identified six putative regions with enhanced population differentiation and four SNPs showed significant clinal variation. The clinal variation at individual SNPs is suggestive of an adaptive response in phyB2 to local photoperiodic conditions. Three of four SNPs showing clinal variation were located in regions with excessive genetic differentiation, demonstrating that searching for regions of high genetic differentiation can be useful for identifying sites putatively involved in local adaptation.     

The challenge of separating signatures of local adaptation from those of isolation by distance and colonization history: The case of two white pines

Accurately detecting signatures of local adaptation using genetic‐environment associations (GEAs) requires controlling for neutral patterns of population structure to reduce the risk of false positives. However, a high degree of collinearity between climatic gradients and neutral population structure can greatly reduce power, and the performance of GEA methods in such case is rarely evaluated in empirical studies. In this study, we attempted to disentangle the effects of local adaptation and isolation by environment (IBE) from those of isolation by distance (IBD) and isolation by colonization from glacial refugia (IBC) using range‐wide samples in two white pine species. For this, SNPs from 168 genes, including 52 candidate genes for growth and phenology, were genotyped in 133 and 61 populations of Pinus strobus and P. monticola, respectively. For P. strobus and using all 153 SNPs, climate (IBE) did not significantly explained among‐population variation when controlling for IBD and IBC in redundancy analyses (RDAs). However, 26 SNPs were significantly associated with climate in single‐locus GEA analyses (Bayenv2 and LFMM), suggesting that local adaptation took place in the presence of high gene flow. For P. monticola, we found no evidence of IBE using RDAs and weaker signatures of local adaptation using GEA and F_ST outlier tests, consistent with adaptation via phenotypic plasticity. In both species, the majority of the explained among‐population variation (69 to 96%) could not be partitioned between the effects of IBE, IBD, and IBC. GEA methods can account differently for this confounded variation, and this could explain the small overlap of SNPs detected between Bayenv2 and LFMM. Our study illustrates the inherent difficulty of taking into account neutral structure in natural populations and the importance of sampling designs that maximize climatic variation, while minimizing collinearity between climatic gradients and neutral structure.     

Cold adaptation in the Asian tiger mosquito's native range precedes its invasion success in temperate regions

Adaptation to environmental conditions within the native range of exotic species can condition the invasion success of these species outside their range. The striking success of the Asian tiger mosquito, Aedes albopictus, to invade temperate regions has been attributed to the winter survival of diapause eggs in cold environments. In this study, we evaluate genetic polymorphisms (SNPs) and wing morphometric variation among three biogeographical regions of the native range of A. albopictus. Reconstructed demographic histories of populations show an initial expansion in Southeast Asia and suggest that marine regression during late Pleistocene and climate warming after the last glacial period favored expansion of populations in southern and northern regions, respectively. Searching for genomic signatures of selection, we identified significantly differentiated SNPs among which several are located in or within 20 kb distance from candidate genes for cold adaptation. These genes involve cellular and metabolic processes and several of them have been shown to be differentially expressed under diapausing conditions. The three biogeographical regions also differ for wing size and shape, and wing size increases with latitude supporting Bergmann's rule. Adaptive genetic and morphometric variation observed along the climatic gradient of A. albopictus native range suggests that colonization of northern latitudes promoted adaptation to cold environments prior to its worldwide invasion.     

Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude.     

Conserving marine biodiversity: insights from life-history trait candidate genes in Atlantic cod (Gadus morhua)

Recent technological developments have facilitated an increased focus on identifying genomic regions underlying adaptive trait variation in natural populations, and it has been advocated that this information should be important for designating population units for conservation. In marine fishes, phenotypic studies have suggested adaptation through divergence of life-history traits among natural populations, but the distribution of adaptive genetic variation in these species is still relatively poorly known. In this study, we extract information about the geographical distribution of genetic variation for 33 single nucleotide polymorphisms (SNPs) associated with life-history trait candidate genes, and compare this to variation in 70 putatively neutral SNPs in Atlantic cod (Gadus morhua). We analyse samples covering the major population complexes in the eastern Atlantic and find strong evidence for non-neutral levels and patterns of population structuring for several of the candidate gene-associated markers, including two SNPs in the growth hormone 1 gene. Thus, this study aligns with findings from phenotypic studies, providing molecular data strongly suggesting that these or closely linked genes are under selection in natural populations of Atlantic cod. Furthermore, we find that patterns of variation in outlier markers do not align with those observed at selectively neutral markers, and that outlier markers identify conservation units on finer geographical scales than those revealed when analysing only neutral markers. Accordingly, results also suggest that information about adaptive genetic variation will be useful for targeted conservation and management in this and other marine species.     

Signatures of local adaptation in lowland and highland teosintes from whole‐genome sequencing of pooled samples

Spatially varying selection triggers differential adaptation of local populations. Here, we mined the determinants of local adaptation at the genomewide scale in the two closest maize wild relatives, the teosintes Zea mays ssp parviglumis and ssp. mexicana. We sequenced 120 individuals from six populations: two lowland, two intermediate and two highland populations sampled along two altitudinal gradients. We detected 8 479 581 single nucleotide polymorphisms (SNPs) covered in the six populations with an average sequencing depth per site per population ranging from 17.0× to 32.2×. Population diversity varied from 0.10 to 0.15, and linkage disequilibrium decayed very rapidly. We combined two differentiation‐based methods, and correlation of allele frequencies with environmental variables to detect outlier SNPs. Outlier SNPs displayed significant clustering. From clusters, we identified 47 candidate regions. We further modified a haplotype‐based method to incorporate genotype uncertainties in haplotype calling, and applied it to candidate regions. We retrieved evidence for selection at the haplotype level in 53% of our candidate regions, and in 70% of the cases the same haplotype was selected in the two lowland or the two highland populations. We recovered a candidate region located within a previously characterized inversion on chromosome 1. We found evidence of a soft sweep at a locus involved in leaf macrohair variation. Finally, our results revealed frequent colocalization between our candidate regions and loci involved in the variation of traits associated with plant–soil interactions such as root morphology, aluminium and low phosphorus tolerance. Soil therefore appears to be a major driver of local adaptation in teosintes.     

The Genomic Architecture of Adaptation to Larval Malnutrition Points to a Trade-off with Adult Starvation Resistance in Drosophila

Periods of nutrient shortage impose strong selection on animal populations. Experimental studies of genetic adaptation to nutrient shortage largely focus on resistance to acute starvation at adult stage; it is not clear how conclusions drawn from these studies extrapolate to other forms of nutritional stress. We studied the genomic signature of adaptation to chronic juvenile malnutrition in six populations of Drosophila melanogaster evolved for 150 generations on an extremely nutrient-poor larval diet. Comparison with control populations evolved on standard food revealed repeatable genomic differentiation between the two set of population, involving >3,000 candidate SNPs forming >100 independently evolving clusters. The candidate genomic regions were enriched in genes implicated in hormone, carbohydrate, and lipid metabolism, including some with known effects on fitness-related life-history traits. Rather than being close to fixation, a substantial fraction of candidate SNPs segregated at intermediate allele frequencies in all malnutrition-adapted populations. This, together with patterns of among-population variation in allele frequencies and estimates of Tajima’s D, suggests that the poor diet results in balancing selection on some genomic regions. Our candidate genes for tolerance to larval malnutrition showed a high overlap with genes previously implicated in acute starvation resistance. However, adaptation to larval malnutrition in our study was associated with reduced tolerance to acute adult starvation. Thus, rather than reflecting synergy, the shared genomic architecture appears to mediate an evolutionary trade-off between tolerances to these two forms of nutritional stress.     

鸡6个功能基因microRNA靶标区域SNP的生物信息学预测

GDF-8、IGF-I、IGF-III、IGF2R、IGFBP2和GHR是鸡的重要经济性状候选基因。利用miRanda和Targetscan软件预测6个基因3′UTR潜在的microRNA靶标, 并发掘靶标区域SNP位点。结果表明: 在6个基因的26个microRNA靶标区域, 共检测到125个SNP位点, 在靶标及其5′和3′邻接等长侧翼区分别检测到47个、44个和35个SNPs位点, 其中12个SNP定位于靶标种子序列互补区。种子序列互补区及其3′侧翼区的SNP位点可能会影响microRNA的调控, 导致家禽的表型变异     

Population genomic footprints of selection and associations with climate in natural populations of Arabidopsis halleri from the Alps

Natural genetic variation is essential for the adaptation of organisms to their local environment and to changing environmental conditions. Here, we examine genomewide patterns of nucleotide variation in natural populations of the outcrossing herb Arabidopsis halleri and associations with climatic variation among populations in the Alps. Using a pooled population sequencing (Pool‐Seq) approach, we discovered more than two million SNPs in five natural populations and identified highly differentiated genomic regions and SNPs using F_ST‐based analyses. We tested only the most strongly differentiated SNPs for associations with a nonredundant set of environmental factors using partial Mantel tests to identify topo‐climatic factors that may underlie the observed footprints of selection. Possible functions of genes showing signatures of selection were identified by Gene Ontology analysis. We found 175 genes to be highly associated with one or more of the five tested topo‐climatic factors. Of these, 23.4% had unknown functions. Genetic variation in four candidate genes was strongly associated with site water balance and solar radiation, and functional annotations were congruent with these environmental factors. Our results provide a genomewide perspective on the distribution of adaptive genetic variation in natural plant populations from a highly diverse and heterogeneous alpine environment.     

Genetic analysis of differentiation among breeding ponds reveals a candidate gene for local adaptation in Rana arvalis

One of the main questions in evolutionary and conservation biology is how geographical and environmental features of the landscape shape neutral and adaptive genetic variation in natural populations. The identification of genomic polymorphisms that account for adaptive variation can aid in finding candidate loci for local adaptation. Consequently, a comparison of spatial patterns in neutral markers and loci under selection may help disentangle the effects of gene flow, genetic drift and selection at the landscape scale. Many amphibians breed in wetlands, which differ in environmental conditions and in the degree of isolation, enhancing the potential for local adaptation. We used microsatellite markers to measure genetic differentiation among 17 local populations of Rana arvalis breeding in a network of wetlands. We found that locus RC08604 deviated from neutral expectations, suggesting that it is a good candidate for directional selection. We used a genetic network analysis to show that the allele distribution in this locus is correlated with habitat characteristics, whereas this was not the case at neutral markers that displayed a different allele distribution and population network in the study area. The graph approach illustrated the genomic heterogeneity (neutral loci vs. the candidate locus for directional selection) of gene exchange and genetic divergence among populations under directional selection. Limited gene flow between wetlands was only observed at the candidate genomic region under directional selection. RC08604 is partially located inside an up‐regulated thyroid‐hormone receptor (TRβ) gene coordinating the expression of other genes during metamorphosis and appears to be linked with variation in larval life‐history traits found among R. arvalis populations. We suggest that directional selection on genes coding larval life‐history traits is strong enough to maintain the divergence in these genomic regions, reducing the effective recombination of locally adapted alleles but not in other regions of the genome. Integrating this knowledge into conservation plans at the landscape scale will improve the design of management strategies to preserve adaptive genetic diversity in wetland networks.     

Connecting genomic patterns of local adaptation and niche suitability in teosintes

The central abundance hypothesis predicts that local adaptation is a function of the distance to the centre of a species’ geographic range. To test this hypothesis, we gathered genomic diversity data from 49 populations, 646 individuals and 33,464 SNPs of two wild relatives of maize, the teosintes Zea mays ssp. parviglumis and Zea. mays. ssp. mexicana. We examined the association between the distance to their climatic and geographic centroids and the enrichment of SNPs bearing signals of adaptation. We identified candidate adaptive SNPs in each population by combining neutrality tests and cline analyses. By applying linear regression models, we found that the number of candidate SNPs is positively associated with niche suitability, while genetic diversity is reduced at the limits of the geographic distribution. Our results suggest that overall, populations located at the limit of the species’ niches are adapting locally. We argue that local adaptation to this limit could initiate ecological speciation processes and facilitate adaptation to global change.     

Genetic Variation and Recent Positive Selection in Worldwide Human Populations: Evidence from Nearly 1 Million SNPs

Background

Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world.

Methodology

We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH). When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental) level.

Conclusions

Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO) analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.     

Linkage mapping of gene-associated SNPs to pig chromosome 11

Single nucleotide polymorphisms (SNPs) were discovered in porcine expressed sequence tags (ESTs) orthologous to genes from human chromosome 13 (HSA13) and predicted to be located on pig chromosome 11 (SSC11). The SNPs were identified as sequence variants in clusters of EST sequences from pig cDNA libraries constructed in the Sino-Danish pig genome project. In total, 312 human gene sequences from HSA13 were used for similarity searches in our pig EST database. Pig ESTs showing significant similarity with HSA13 genes were clustered and candidate SNPs were identified. Allele frequencies for 26 SNPs were estimated in a group of 80 unrelated pigs from Danish commercial pig breeds: Duroc, Hampshire, Landrace and Large White. Eighteen of the 26 SNPs genotyped in the PiGMaP Reference Families were mapped by linkage analysis to SSC11. The EST-based SNPs published here are new genetic markers useful for linkage and association studies in commercial and experimental pig populations. This study represents the first gene-associated SNP linkage map of pig chromosome 11 and adds new comparative mapping information between SSC11 and HSA13. Furthermore, our data facilitate future studies aimed at the identification of interesting regions on pig chromosome 11, positional cloning and fine mapping of quantitative trait loci in pig.     

A low-density SNP array for analyzing differential selection in freshwater and marine populations of threespine stickleback (Gasterosteus aculeatus)

Background

The threespine stickleback (Gasterosteus aculeatus) has become an important model species for studying both contemporary and parallel evolution. In particular, differential adaptation to freshwater and marine environments has led to high differentiation between freshwater and marine stickleback populations at the phenotypic trait of lateral plate morphology and the underlying candidate gene Ectodysplacin (EDA). Many studies have focused on this trait and candidate gene, although other genes involved in marine-freshwater adaptation may be equally important. In order to develop a resource for rapid and cost efficient analysis of genetic divergence between freshwater and marine sticklebacks, we generated a low-density SNP (Single Nucleotide Polymorphism) array encompassing markers of chromosome regions under putative directional selection, along with neutral markers for background.

Results

RAD (Restriction site Associated DNA) sequencing of sixty individuals representing two freshwater and one marine population led to the identification of 33,993 SNP markers. Ninety-six of these were chosen for the low-density SNP array, among which 70 represented SNPs under putatively directional selection in freshwater vs. marine environments, whereas 26 SNPs were assumed to be neutral. Annotation of these regions revealed several genes that are candidates for affecting stickleback phenotypic variation, some of which have been observed in previous studies whereas others are new.

Conclusions

We have developed a cost-efficient low-density SNP array that allows for rapid screening of polymorphisms in threespine stickleback. The array provides a valuable tool for analyzing adaptive divergence between freshwater and marine stickleback populations beyond the well-established candidate gene Ectodysplacin (EDA).

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-867) contains supplementary material, which is available to authorized users.     

In the presence of population structure: From genomics to candidate genes underlying local adaptation

Understanding the genomic signatures, genes, and traits underlying local adaptation of organisms to heterogeneous environments is of central importance to the field evolutionary biology. To identify loci underlying local adaptation, models that combine allelic and environmental variation while controlling for the effects of population structure have emerged as the method of choice. Despite being evaluated in simulation studies, there has not been a thorough investigation of empirical evidence supporting local adaptation across these alleles. To evaluate these methods, we use 875 Arabidopsis thaliana Eurasian accessions and two mixed models (GEMMA and LFMM) to identify candidate SNPs underlying local adaptation to climate. Subsequently, to assess evidence of local adaptation and function among significant SNPs, we examine allele frequency differentiation and recent selection across Eurasian populations, in addition to their distribution along quantitative trait loci (QTL) explaining fitness variation between Italy and Sweden populations and cis‐regulatory/nonsynonymous sites showing significant selective constraint. Our results indicate that significant LFMM/GEMMA SNPs show low allele frequency differentiation and linkage disequilibrium across locally adapted Italy and Sweden populations, in addition to a poor association with fitness QTL peaks (highest logarithm of odds score). Furthermore, when examining derived allele frequencies across the Eurasian range, we find that these SNPs are enriched in low‐frequency variants that show very large climatic differentiation but low levels of linkage disequilibrium. These results suggest that their enrichment along putative functional sites most likely represents deleterious variation that is independent of local adaptation. Among all the genomic signatures examined, only SNPs showing high absolute allele frequency differentiation (AFD) and linkage disequilibrium (LD) between Italy and Sweden populations showed a strong association with fitness QTL peaks and were enriched along selectively constrained cis‐regulatory/nonsynonymous sites. Using these SNPs, we find strong evidence linking flowering time, freezing tolerance, and the abscisic‐acid pathway to local adaptation.     

Genomic Patterns of Geographic Differentiation in Drosophila simulans

Geographic patterns of genetic differentiation have long been used to understand population history and to learn about the biological mechanisms of adaptation. Here we present an examination of genomic patterns of differentiation between northern and southern populations of Australian and North American Drosophila simulans, with an emphasis on characterizing signals of parallel differentiation. We report on the genomic scale of differentiation and functional enrichment of outlier SNPs. While, overall, signals of shared differentiation are modest, we find the strongest support for parallel differentiation in genomic regions that are associated with regulation. Comparisons to Drosophila melanogaster yield potential candidate genes involved in local adaptation in both species, providing insight into common selective pressures and responses. In contrast to D. melanogaster, in D. simulans we observe patterns of variation that are inconsistent with a model of temperate adaptation out of a tropical ancestral range, highlighting potential differences in demographic and colonization histories of this cosmopolitan species pair.