Hypoxia Inducible Factor pathway proteins in high-altitude mammals.

Humans and other mammals inhabit hypoxic high-altitude locales. In many of these species, genes under positive selection include ones in the Hypoxia Inducible Factor (HIF) pathway. One is PHD2 (EGLN1), which encodes for a key oxygen sensor. Another is HIF2A (EPAS1), which encodes for a PHD2-regulated transcription factor. Recent studies have provided insights into mechanisms for these high-altitude alleles. These studies have (i) shown that selection can occur on nonconserved, unstructured regions of proteins, (ii) revealed that high altitude-associated amino acid substitutions can have differential effects on protein-protein interactions, (iii) provided evidence for convergent evolution by different molecular mechanisms, and (iv) suggested that mutations in different genes can complement one another to produce a set of adaptive phenotypes.

Genetic adaptations of marine invertebrates to hydrothermal vent habitats.

Hydrothermal vents are unique habitats like an oases of life compared with typical deep-sea, soft-sediment environments. Most animals that live in these habitats are invertebrates, and they have adapted to extreme vent environments that include high temperatures, hypoxia, high sulfide, high metal concentration, and darkness. The advent of next-generation sequencing technology, especially the coming of the new era of omics, allowed more studies to focus on the molecular adaptation of these invertebrates to vent habitats. Many genes linked to hydrothermal adaptation have been studied. We summarize the findings related to these genetic adaptations and discuss which new techniques can facilitate studies in the future.

Exploring Adaptive Phenotypes for the Human Calcium-Sensing Receptor Polymorphism R990G.

Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the calcium-sensing receptor gene in Southeast Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up. Although the calcium-sensing receptor has a critical role in calcium homeostasis by directly regulating the parathyroid hormone secretion, it is expressed in different tissues and has been described to be involved in many biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mouse homozygous for the derived allele show not only lower serum calcium concentration but also greater body weight and fat accumulation, probably because of enhanced preadipocyte differentiation and lipolysis impairment resulting from the calcium-sensing receptor activation mediated by R990G. We speculate that such differential features in humans could have facilitated the survival of hunter-gatherer groups during periods of nutritional stress in the challenging conditions of the Southeast Asian tropical rainforests.

Non-genetic and genetic rewiring underlie adaptation to hypomorphic alleles of an essential gene.

Adaptive evolution to cellular stress is a process implicated in a wide range of biological and clinical phenomena. Two major routes of adaptation have been identified: non-genetic changes, which allow expression of different phenotypes in novel environments, and genetic variation achieved by selection of fitter phenotypes. While these processes are broadly accepted, their temporal and epistatic features in the context of cellular evolution and emerging drug resistance are contentious. In this manuscript, we generated hypomorphic alleles of the essential nuclear pore complex (NPC) gene NUP58. By dissecting early and long-term mechanisms of adaptation in independent clones, we observed that early physiological adaptation correlated with transcriptome rewiring and upregulation of genes known to interact with the NPC; long-term adaptation and fitness recovery instead occurred via focal amplification of NUP58 and restoration of mutant protein expression. These data support the concept that early phenotypic plasticity allows later acquisition of genetic adaptations to a specific impairment. We propose this approach as a genetic model to mimic targeted drug therapy in human cells and to dissect mechanisms of adaptation.

The genomic signatures of natural selection in admixed human populations.

Admixture has been a pervasive phenomenon in human history, extensively shaping the patterns of population genetic diversity. There is increasing evidence to suggest that admixture can also facilitate genetic adaptation to local environments, i.e., admixed populations acquire beneficial mutations from source populations, a process that we refer to as "adaptive admixture." However, the role of adaptive admixture in human evolution and the power to detect it remain poorly characterized. Here, we use extensive computer simulations to evaluate the power of several neutrality statistics to detect natural selection in the admixed population, assuming multiple admixture scenarios. We show that statistics based on admixture proportions, Fadm and LAD, show high power to detect mutations that are beneficial in the admixed population, whereas other statistics, including iHS and FST, falsely detect neutral mutations that have been selected in the source populations only. By combining Fadm and LAD into a single, powerful statistic, we scanned the genomes of 15 worldwide, admixed populations for signatures of adaptive admixture. We confirm that lactase persistence and resistance to malaria have been under adaptive admixture in West Africans and in Malagasy, North Africans, and South Asians, respectively. Our approach also uncovers other cases of adaptive admixture, including APOL1 in Fulani nomads and PKN2 in East Indonesians, involved in resistance to infection and metabolism, respectively. Collectively, our study provides evidence that adaptive admixture has occurred in human populations whose genetic history is characterized by periods of isolation and spatial expansions resulting in increased gene flow.

Comparative Population Transcriptomics Provide New Insight into the Evolutionary History and Adaptive Potential of World Ocean Krill.

Genetic variation is instrumental for adaptation to changing environments but it is unclear how it is structured and contributes to adaptation in pelagic species lacking clear barriers to gene flow. Here, we applied comparative genomics to extensive transcriptome datasets from 20 krill species collected across the Atlantic, Indian, Pacific, and Southern Oceans. We compared genetic variation both within and between species to elucidate their evolutionary history and genomic bases of adaptation. We resolved phylogenetic interrelationships and uncovered genomic evidence to elevate the cryptic Euphausia similis var. armata into species. Levels of genetic variation and rates of adaptive protein evolution vary widely. Species endemic to the cold Southern Ocean, such as the Antarctic krill Euphausia superba, showed less genetic variation and lower evolutionary rates than other species. This could suggest a low adaptive potential to rapid climate change. We uncovered hundreds of candidate genes with signatures of adaptive evolution among Antarctic Euphausia but did not observe strong evidence of adaptive convergence with the predominantly Arctic Thysanoessa. We instead identified candidates for cold-adaptation that have also been detected in Antarctic fish, including genes that govern thermal reception such as TrpA1. Our results suggest parallel genetic responses to similar selection pressures across Antarctic taxa and provide new insights into the adaptive potential of important zooplankton already affected by climate change.

Genetic adaptation despite high gene flow in a range-expanding population.

Signals of natural selection can be quickly eroded in high gene flow systems, curtailing efforts to understand how and when genetic adaptation occurs in the ocean. This long-standing, unresolved topic in ecology and evolution has renewed importance because changing environmental conditions are driving range expansions that may necessitate rapid evolutionary responses. One example occurs in Kellet's whelk (Kelletia kelletii), a common subtidal gastropod with an ~40- to 60-day pelagic larval duration that expanded their biogeographic range northwards in the 1970s by over 300 km. To test for genetic adaptation, we performed a series of experimental crosses with Kellet's whelk adults collected from their historical (HxH) and recently expanded range (ExE), and conducted RNA-Seq on offspring that we reared in a common garden environment. We identified 2770 differentially expressed genes (DEGs) between 54 offspring samples with either only historical range (HxH offspring) or expanded range (ExE offspring) ancestry. Using SNPs called directly from the DEGs, we assigned samples of known origin back to their range of origin with unprecedented accuracy for a marine species (92.6% and 94.5% for HxH and ExE offspring, respectively). The SNP with the highest predictive importance occurred on triosephosphate isomerase (TPI), an essential metabolic enzyme involved in cold stress response. TPI was significantly upregulated and contained a non-synonymous mutation in the expanded range. Our findings pave the way for accurately identifying patterns of dispersal, gene flow and population connectivity in the ocean by demonstrating that experimental transcriptomics can reveal mechanisms for how marine organisms respond to changing environmental conditions.

Predicting the Combined Effects of Multiple Stressors and Stress Adaptation in Gammarus pulex.

Global change confronts organisms with multiple stressors causing nonadditive effects. Persistent stress, however, leads to adaptation and related trade-offs. The question arises: How can the resulting effects of these contradictory processes be predicted? Here we show that Gammarus pulex from agricultural streams were more tolerant to clothianidin (mean EC50 148 µg/L) than populations from reference streams (mean EC50 67 µg/L). We assume that this increased tolerance results from a combination of physiological acclimation, epigenetic effects, and genetic evolution, termed as adaptation. Further, joint exposure to pesticide mixture and temperature stress led to synergistic interactions of all three stressors. However, these combined effects were significantly stronger in adapted populations as shown by the model deviation ratio (MDR) of 4, compared to reference populations (MDR = 2.7). The pesticide adaptation reduced the General-Stress capacity of adapted individuals, and the related trade-off process increased vulnerability to combined stress. Overall, synergistic interactions were stronger with increasing total stress and could be well predicted by the stress addition model (SAM). In contrast, traditional models such as concentration addition (CA) and effect addition (EA) substantially underestimated the combined effects. We conclude that several, even very disparate stress factors, including population adaptations to stress, can act synergistically. The strong synergistic potential underscores the critical importance of correctly predicting multiple stresses for risk assessment.

Genome Resequencing Reveals Rapid, Repeated Evolution in the Colorado Potato Beetle.

Insecticide resistance and rapid pest evolution threatens food security and the development of sustainable agricultural practices, yet the evolutionary mechanisms that allow pests to rapidly adapt to control tactics remains unclear. Here, we examine how a global super-pest, the Colorado potato beetle (CPB), Leptinotarsa decemlineata, rapidly evolves resistance to insecticides. Using whole-genome resequencing and transcriptomic data focused on its ancestral and pest range in North America, we assess evidence for three, nonmutually exclusive models of rapid evolution: pervasive selection on novel mutations, rapid regulatory evolution, and repeated selection on standing genetic variation. Population genomic analysis demonstrates that CPB is geographically structured, even among recently established pest populations. Pest populations exhibit similar levels of nucleotide diversity, relative to nonpest populations, and show evidence of recent expansion. Genome scans provide clear signatures of repeated adaptation across CPB populations, with especially strong evidence of selection on insecticide resistance genes in different populations. Analyses of gene expression show that constitutive upregulation of candidate insecticide resistance genes drives distinctive population patterns. CPB evolves insecticide resistance repeatedly across agricultural regions, leveraging similar genetic pathways but different genes, demonstrating a polygenic trait architecture for insecticide resistance that can evolve from standing genetic variation. Despite expectations, we do not find support for strong selection on novel mutations, or rapid evolution from selection on regulatory genes. These results suggest that integrated pest management practices must mitigate the evolution of polygenic resistance phenotypes among local pest populations, in order to maintain the efficacy and sustainability of novel control techniques.

The Genomics of Human Local Adaptation.

Modern humans inhabit a variety of environments and are exposed to a plethora of selective pressures, leading to multiple genetic adaptations to local environmental conditions. These include adaptations to climate, UV exposure, disease, diet, altitude, or cultural practice and have generated important genetic and phenotypic differences amongst populations. In recent years, new methods to identify the genomic signatures of natural selection underlying these adaptations, combined with novel types of genetic data (e.g., ancient DNA), have provided unprecedented insights into the origin of adaptive alleles and the modes of adaptation. As a result, numerous instances of local adaptation have been identified in humans. Here, we review the most exciting recent developments and discuss, in our view, the future of this field.

Rapid genetic adaptation to a novel ecosystem despite a large founder event.

Introduced and invasive species make excellent natural experiments for investigating rapid evolution. Here, we describe the effects of genetic drift and rapid genetic adaptation in pink salmon (Oncorhynchus gorbuscha) that were accidentally introduced to the Great Lakes via a single introduction event 31 generations ago. Using whole-genome resequencing for 134 fish spanning five sample groups across the native and introduced range, we estimate that the source population's effective population size was 146,886 at the time of introduction, whereas the founding population's effective population size was just 72-a 2040-fold decrease. As expected with a severe founder event, we show reductions in genome-wide measures of genetic diversity, specifically a 37.7% reduction in the number of SNPs and an 8.2% reduction in observed heterozygosity. Despite this decline in genetic diversity, we provide evidence for putative selection at 47 loci across multiple chromosomes in the introduced populations, including missense variants in genes associated with circadian rhythm, immunological response and maturation, which match expected or known phenotypic changes in the Great Lakes. For one of these genes, we use a species-specific agent-based model to rule out genetic drift and conclude our results support a strong response to selection occurring in a period gene (per2) that plays a predominant role in determining an organism's daily clock, matching large day length differences experienced by introduced salmon during important phenological periods. Together, these results inform how populations might evolve rapidly to new environments, even with a small pool of standing genetic variation.

Complementary genomic and epigenomic adaptation to environmental heterogeneity.

While adaptation is commonly thought to result from selection on DNA sequence-based variation, recent studies have highlighted an analogous epigenetic component as well. However, the relative roles of these mechanisms in facilitating population persistence under environmental heterogeneity remain unclear. To address the underlying genetic and epigenetic mechanisms and their relationship during environmental adaptation, we screened the genomes and epigenomes of nine global populations of a predominately sessile marine invasive tunicate, Botryllus schlosseri. We detected clear population differentiation at the genetic and epigenetic levels. Patterns of genetic and epigenetic structure were significantly influenced by local environmental variables. Among these variables, minimum annual sea surface temperature was identified as the top explanatory variable for both genetic and epigenetic variation. However, patterns of population structure driven by genetic and epigenetic variation were somewhat distinct, suggesting possible autonomy of epigenetic variation. We found both shared and specific genes and biological pathways among genetic and epigenetic loci associated with environmental factors, consistent with complementary and independent contributions of genetic and epigenetic variation to environmental adaptation in this system. Collectively, these mechanisms may facilitate population persistence under environmental change and sustain successful invasions across novel environments.

Whole genome resequencing reveals signatures of rapid selection in a virus-affected commercial fishery.

Infectious diseases are recognized as one of the greatest global threats to biodiversity and ecosystem functioning. Consequently, there is a growing urgency to understand the speed at which adaptive phenotypes can evolve and spread in natural populations to inform future management. Here we provide evidence of rapid genomic changes in wild Australian blacklip abalone (Haliotis rubra) following a major population crash associated with an infectious disease. Genome scans on H. rubra were performed using pooled whole genome resequencing data from commercial fishing stocks varying in historical exposure to haliotid herpesvirus-1 (HaHV-1). Approximately 25,000 single nucleotide polymorphism loci associated with virus exposure were identified, many of which mapped to genes known to contribute to HaHV-1 immunity in the New Zealand paua (Haliotis iris) and herpesvirus response pathways in haliotids and other animal systems. These findings indicate genetic changes across a single generation in H. rubra fishing stocks decimated by HaHV-1, with stock recovery potentially determined by rapid evolutionary changes leading to virus resistance. This is a novel example of apparently rapid adaptation in natural populations of a nonmodel marine organism, highlighting the pace at which selection can potentially act to counter disease in wildlife communities.

Dynamic Pneumococcal Genetic Adaptations Support Bacterial Growth and Inflammation during Coinfection with Influenza.

Streptococcus pneumoniae (pneumococcus) is one of the primary bacterial pathogens that complicates influenza virus infections. These bacterial coinfections increase influenza-associated morbidity and mortality through a number of immunological and viral-mediated mechanisms, but the specific bacterial genes that contribute to postinfluenza pathogenicity are not known. Here, we used genome-wide transposon mutagenesis (Tn-Seq) to reveal bacterial genes that confer improved fitness in influenza virus-infected hosts. The majority of the 32 genes identified are involved in bacterial metabolism, including nucleotide biosynthesis, amino acid biosynthesis, protein translation, and membrane transport. We generated mutants with single-gene deletions (SGD) of five of the genes identified, SPD1414, SPD2047 (cbiO1), SPD0058 (purD), SPD1098, and SPD0822 (proB), to investigate their effects on in vivo fitness, disease severity, and host immune responses. The growth of the SGD mutants was slightly attenuated in vitro and in vivo, but each still grew to high titers in the lungs of mock- and influenza virus-infected hosts. Despite high bacterial loads, mortality was significantly reduced or delayed with all SGD mutants. Time-dependent reductions in pulmonary neutrophils, inflammatory macrophages, and select proinflammatory cytokines and chemokines were also observed. Immunohistochemical staining further revealed altered neutrophil distribution with reduced degeneration in the lungs of influenza virus-SGD mutant-coinfected animals. These studies demonstrate a critical role for specific bacterial genes and for bacterial metabolism in driving virulence and modulating immune function during influenza-associated bacterial pneumonia.

Rapid genetic adaptation to recently colonized environments is driven by genes underlying life history traits.

BACKGROUND: Uncovering the mechanisms underlying rapid genetic adaptation can provide insight into adaptive evolution and shed light on conservation, invasive species control, and natural resource management. However, it can be difficult to experimentally explore rapid adaptation due to the challenges associated with propagating and maintaining species in captive environments for long periods of time. By contrast, many introduced species have experienced strong selection when colonizing environments that differ substantially from their native range and thus provide a "natural experiment" for studying rapid genetic adaptation. One such example occurred when sea lamprey (Petromyzon marinus), native to the northern Atlantic, naturally migrated into Lake Champlain and expanded their range into the Great Lakes via man-made shipping canals. RESULTS: Utilizing 368,886 genome-wide single nucleotide polymorphisms (SNPs), we calculated genome-wide levels of genetic diversity (i.e., heterozygosity and π) for sea lamprey collected from native (Connecticut River), native but recently colonized (Lake Champlain), and invasive (Lake Michigan) populations, assessed genetic differentiation between all populations, and identified candidate genes that responded to selection imposed by the novel environments. We observed a 14 and 24% reduction in genetic diversity in Lake Michigan and Lake Champlain populations, respectively, compared to individuals from the Connecticut River, suggesting that sea lamprey populations underwent a genetic bottleneck during colonization. Additionally, we identified 121 and 43 outlier genes in comparisons between Lake Michigan and Connecticut River and between Lake Champlain and Connecticut River, respectively. Six outlier genes that contained synonymous SNPs in their coding regions and two genes that contained nonsynonymous SNPs may underlie the rapid evolution of growth (i.e., GHR), reproduction (i.e., PGR, TTC25, STARD10), and bioenergetics (i.e., OXCT1, PYGL, DIN4, SLC25A15). CONCLUSIONS: By identifying the genomic basis of rapid adaptation to novel environments, we demonstrate that populations of invasive species can be a useful study system for understanding adaptive evolution. Furthermore, the reduction in genome-wide levels of genetic diversity associated with colonization coupled with the identification of outlier genes underlying key life history traits known to have changed in invasive sea lamprey populations (e.g., growth, reproduction) illustrate the utility in applying genomic approaches for the successful management of introduced species.

Temperature, rainfall and wind variables underlie environmental adaptation in natural populations of Drosophila melanogaster.

While several studies in a diverse set of species have shed light on the genes underlying adaptation, our knowledge on the selective pressures that explain the observed patterns lags behind. Drosophila melanogaster is a valuable organism to study environmental adaptation because this species originated in Southern Africa and has recently expanded worldwide, and also because it has a functionally well-annotated genome. In this study, we aimed to decipher which environmental variables are relevant for adaptation of D. melanogaster natural populations in Europe and North America. We analysed 36 whole-genome pool-seq samples of D. melanogaster natural populations collected in 20 European and 11 North American locations. We used the BayPass software to identify single nucleotide polymorphisms (SNPs) and transposable elements (TEs) showing signature of adaptive differentiation across populations, as well as significant associations with 59 environmental variables related to temperature, rainfall, evaporation, solar radiation, wind, daylight hours, and soil type. We found that in addition to temperature and rainfall, wind related variables are also relevant for D. melanogaster environmental adaptation. Interestingly, 23%-51% of the genes that showed significant associations with environmental variables were not found overly differentiated across populations. In addition to SNPs, we also identified 10 reference transposable element insertions associated with environmental variables. Our results showed that genome-environment association analysis can identify adaptive genetic variants that are undetected by population differentiation analysis while also allowing the identification of candidate environmental drivers of adaptation.

The role of genome duplication in big sagebrush growth and fecundity.

PREMISE: Adaptive traits can be dramatically altered by genome duplication. The study of interactions among traits, ploidy, and the environment are necessary to develop an understanding of how polyploidy affects niche differentiation and to develop restoration strategies for resilient native ecosystems. METHODS: Growth and fecundity were measured in common gardens for 39 populations of big sagebrush (Artemisia tridentata) containing two subspecies and two ploidy levels. General linear mixed-effect models assessed how much of the trait variation could be attributed to genetics (i.e., ploidy and climatic adaptation), environment, and gene-environment interactions. RESULTS: Growth and fecundity variation were explained well by the mixed models (80% and 91%, respectively). Much of the trait variation was attributed to environment, and 15% of variation in growth and 34% of variation in seed yield were attributed to genetics. Genetic trait variation was mostly attributable to ploidy, with much higher growth and seed production in diploids, even in a warm-dry environment typically dominated by tetraploids. Population-level genetic variation was also evident and was related to the climate of each population's origin. CONCLUSIONS: Ploidy is a strong predictor growth and seed yield, regardless of common-garden environment. The superior growth and fecundity of diploids across environments raises the question as to how tetraploids can be more prevalent than diploids, especially in warm-dry environments. Two hypotheses that may explain the abundance of tetraploids on the landscape include selection for drought resistance at the seedling stage, and greater competitive ability in water uptake in the upper soil horizon.

Genomic Assessment of Global Population Structure in a Highly Migratory and Habitat Versatile Apex Predator, the Tiger Shark (Galeocerdo cuvier).

Understanding the population dynamics of highly mobile, widely distributed, oceanic sharks, many of which are overexploited, is necessary to aid their conservation management. We investigated the global population genomics of tiger sharks (Galeocerdo cuvier), a circumglobally distributed, apex predator displaying remarkable behavioral versatility in its diet, habitat use (near coastal, coral reef, pelagic), and individual movement patterns (spatially resident to long-distance migrations). We genotyped 242 tiger sharks from 10 globally distributed locations at more than 2000 single nucleotide polymorphisms. Although this species often conducts massive distance migrations, the data show strong genetic differentiation at both neutral (FST = 0.125-0.144) and candidate outlier loci (FST = 0.570-0.761) between western Atlantic and Indo-Pacific sharks, suggesting the potential for adaptation to the environments specific to these oceanic regions. Within these regions, there was mixed support for population differentiation between northern and southern hemispheres in the western Atlantic, and none for structure within the Indian Ocean. Notably, the results demonstrate a low level of population differentiation of tiger sharks from the remote Hawaiian archipelago compared with sharks from the Indian Ocean (FST = 0.003-0.005, P < 0.01). Given concerns about biodiversity loss and marine ecosystem impacts caused by overfishing of oceanic sharks in the midst of rapid environmental change, our results suggest it imperative that international fishery management prioritize conservation of the evolutionary potential of the highly genetically differentiated Atlantic and Indo-Pacific populations of this unique apex predator. Furthermore, we suggest targeted management attention to tiger sharks in the Hawaiian archipelago based on a precautionary biodiversity conservation perspective.

Genotype-environment interactions rule the response of a widespread butterfly to temperature variation.

Understanding how organisms adapt to complex environments is a central goal of evolutionary biology and ecology. This issue is of special interest in the current era of rapidly changing climatic conditions. Here, we investigate clinal variation and plastic responses in life history, morphology and physiology in the butterfly Pieris napi along a pan-European gradient by exposing butterflies raised in captivity to different temperatures. We found clinal variation in body size, growth rates and concomitant development time, wing aspect ratio, wing melanization and heat tolerance. Individuals from warmer environments were more heat-tolerant and had less melanised wings and a shorter development, but still they were larger than individuals from cooler environments. These findings suggest selection for rapid growth in the warmth and for wing melanization in the cold, and thus fine-tuned genetic adaptation to local climates. Irrespective of the origin of butterflies, the effects of higher developmental temperature were largely as expected, speeding up development; reducing body size, potential metabolic activity and wing melanization; while increasing heat tolerance. At least in part, these patterns likely reflect adaptive phenotypic plasticity. In summary, our study revealed pronounced plastic and genetic responses, which may indicate high adaptive capacities in our study organism. Whether this may help such species, though, to deal with current climate change needs further investigation, as clinal patterns have typically evolved over long periods.

Parallel adaptive evolution of geographically distant herring populations on both sides of the North Atlantic Ocean.

Atlantic herring is an excellent species for studying the genetic basis of adaptation in geographically distant populations because of its characteristically large population sizes and low genetic drift. In this study we compared whole-genome resequencing data of Atlantic herring populations from both sides of the Atlantic Ocean. An important finding was the very low degree of genetic differentiation among geographically distant populations (fixation index = 0.026), suggesting lack of reproductive isolation across the ocean. This feature of the Atlantic herring facilitates the detection of genetic factors affecting adaptation because of the sharp contrast between loci showing genetic differentiation resulting from natural selection and the low background noise resulting from genetic drift. We show that genetic factors associated with timing of reproduction are shared between genetically distinct and geographically distant populations. The genes for thyroid-stimulating hormone receptor (TSHR), the SOX11 transcription factor (SOX11), calmodulin (CALM), and estrogen receptor 2 (ESR2A), all with a significant role in reproductive biology, were among the loci that showed the most consistent association with spawning time throughout the species range. In fact, the same two SNPs located at the 5' end of TSHR showed the most significant association with spawning time in both the east and west Atlantic. We also identified unexpected haplotype sharing between spring-spawning oceanic herring and autumn-spawning populations across the Atlantic Ocean and the Baltic Sea. The genomic regions showing this pattern are unlikely to control spawning time but may be involved in adaptation to ecological factor(s) shared among these populations.