Population interconnectivity over the past 120,000 years explains distribution and diversity of Central African hunter-gatherers

The evolutionary history of African hunter-gatherers holds key insights into modern human diversity. Here, we combine ethnographic and genetic data on Central African hunter-gatherers (CAHG) to show that their current distribution and density are explained by ecology rather than by a displacement to marginal habitats due to recent farming expansions, as commonly assumed. We also estimate the range of hunter-gatherer presence across Central Africa over the past 120,000 years using paleoclimatic reconstructions, which were statistically validated by our newly compiled dataset of dated archaeological sites. Finally, we show that genomic estimates of divergence times between CAHG groups match our ecological estimates of periods favoring population splits, and that recoveries of connectivity would have facilitated subsequent gene flow. Our results reveal that CAHG stem from a deep history of partially connected populations. This form of sociality allowed the coexistence of relatively large effective population sizes and local differentiation, with important implications for the evolution of genetic and cultural diversity in Homo sapiens.

The evolutionary history of African hunter-gatherers may hold key insights into patterns and processes behind the evolution of modern human diversity. Recent genomic studies have revealed that these populations represent the oldest and most diverse human genetic lineages and have been genetically differentiated from one another since the origin of humans (1–3) (SI Appendix, Table S1). Therefore, a first question is whether their current ecological niches were also characteristic of early Homo sapiens populations. However, genetic data alone can neither determine the geographic distribution of hunter-gatherers in the past nor demonstrate a deep history of adaptation of hunter-gatherers to their current environments. In fact, various studies have proposed that farming expansions within the past 5,000 years (in particular by the ancestors of Bantu speakers) would have only recently displaced hunter-gatherers to marginalized regions less favorable to agriculture (such as rainforests and deserts) (4–7).For example, the central part of Africa, between latitudes 5°N and 5°S currently is inhabited by ∼20 scattered hunter-gatherer ethnic groups (8). These Central African hunter-gatherers (CAHG) form a genetic clade thought to have diverged from other African populations as far back as 120,000 to 200,000 years ago (2, 9). The lack of any major linguistic specificity between them is often implied to reflect extensive contacts with surrounding farmer populations (8, 10), and seen as evidence of recent displacement into marginal forest environments by expanding farming populations. However, anthropologists have remarked on the huge variability in lifestyle, habitat, techniques, and tools between CAHG (11), suggestive of long-term cultural diversification and adaptation to forest environments. Research on the drivers of demography and adaptation of CAHG populations remains extremely limited, which can be partially attributed to the lack of archaeological and osteological data resulting from a rapid disintegration of fossil remains in the rainforest’s acidic soils, in addition to social instability in the region (12). Therefore, we are still left with crucial questions regarding the time depth of occupation of Central Africa by hunter-gatherers, the breadth of the niche exploited by earlier populations in the region, and variations in levels of interconnectivity at different points in time.To address those questions, we first compiled ethnographic data on the distribution of 749 camps from 11 hunter-gatherer groups extending from West to East Central Africa. We used them as inputs for environmental niche models (ENMs) to determine the relative influence of several bioclimatic and ecological factors, as well as the presence of farming populations, on the distribution and abundance of CAHG (13, 14). Then, we used high-resolution paleoclimatic reconstructions and topographic maps to make continuous predictions about where CAHG could have lived over the past 120,000 years and the potential extension of their interaction networks. Next, we compiled all reliably dated archaeological assemblages ascribed to hunter-gatherer groups in the Congo Basin (n = 168) and confirmed the model’s ability to predict the location and date of the sites. We further contextualized genomic estimates of population divergences with changes in population densities and interpopulation connectivity predicted by our model. Last, we complemented these analyses with a detailed assessment of present and historical gene flow between nine CAHG populations (n = 265 individuals), which we used to assess recent interactions between previously diverged CAHG populations, after farming expansions. Our study therefore provides a causal link between past environmental changes and human population dynamics over evolutionary time, by predicting where and when populations across Central Africa could have exchanged genetic and/or cultural information throughout their evolutionary history.     

Genome-wide patterns of population structure and admixture in West Africans and African Americans

Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans (n = 365) and individuals with ancestry from West Africa (n = 203 from 12 populations) and Europe (n = 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion. Among African Americans, analysis of genomic admixture by a principal component-based approach indicates that the median proportion of European ancestry is 18.5% (25th–75th percentiles: 11.6–27.7%), with very large variation among individuals. In the African-American sample as a whole, few autosomal regions showed exceptionally high or low mean African ancestry, but the X chromosome showed elevated levels of African ancestry, consistent with a sex-biased pattern of gene flow with an excess of European male and African female ancestry. We also find that genomic profiles of individual African Americans afford personalized ancestry reconstructions differentiating ancient vs. recent European and African ancestry. Finally, patterns of genetic similarity among inferred African segments of African-American genomes and genomes of contemporary African populations included in this study suggest African ancestry is most similar to non-Bantu Niger-Kordofanian-speaking populations, consistent with historical documents of the African Diaspora and trans-Atlantic slave trade.     

Particularism and the retreat from theory in the archaeology of agricultural origins

The introduction of new analytic methods and expansion of research into previously untapped regions have greatly increased the scale and resolution of data relevant to the origins of agriculture (OA). As a result, the recognition of varied historical pathways to agriculture and the continuum of management strategies have complicated the search for general explanations for the transition to food production. In this environment, higher-level theoretical frameworks are sometimes rejected on the grounds that they force conclusions that are incompatible with real-world variability. Some of those who take this position argue instead that OA should be explained in terms of local and historically contingent factors. This retreat from theory in favor of particularism is based on the faulty beliefs that complex phenomena such as agricultural origins demand equally complex explanations and that explanation is possible in the absence of theoretically based assumptions. The same scholars who are suspicious of generalization are reluctant to embrace evolutionary approaches to human behavior on the grounds that they are ahistorical, overly simplistic, and dismissive of agency and intent. We argue that these criticisms are misplaced and explain why a coherent theory of human behavior that acknowledges its evolutionary history is essential to advancing understanding of OA. Continued progress depends on the integration of human behavior and culture into the emerging synthesis of evolutionary developmental biology that informs contemporary research into plant and animal domestication.     

Biogeography of the Sulfolobus islandicus pan-genome

Variation in gene content has been hypothesized to be the primary mode of adaptive evolution in microorganisms; however, very little is known about the spatial and temporal distribution of variable genes. Through population-scale comparative genomics of 7 Sulfolobus islandicus genomes from 3 locations, we demonstrate the biogeographical structure of the pan-genome of this species, with no evidence of gene flow between geographically isolated populations. The evolutionary independence of each population allowed us to assess genome dynamics over very recent evolutionary time, beginning ≈910,000 years ago. On this time scale, genome variation largely consists of recent strain-specific integration of mobile elements. Localized sectors of parallel gene loss are identified; however, the balance between the gain and loss of genetic material suggests that S. islandicus genomes acquire material slowly over time, primarily from closely related Sulfolobus species. Examination of the genome dynamics through population genomics in S. islandicus exposes the process of allopatric speciation in thermophilic Archaea and brings us closer to a generalized framework for understanding microbial genome evolution in a spatial context.     

Mobile elements reveal small population size in the ancient ancestors of Homo sapiens

The genealogies of different genetic loci vary in depth. The deeper the genealogy, the greater the chance that it will include a rare event, such as the insertion of a mobile element. Therefore, the genealogy of a region that contains a mobile element is on average older than that of the rest of the genome. In a simple demographic model, the expected time to most recent common ancestor (TMRCA) is doubled if a rare insertion is present. We test this expectation by examining single nucleotide polymorphisms around polymorphic Alu insertions from two completely sequenced human genomes. The estimated TMRCA for regions containing a polymorphic insertion is two times larger than the genomic average (P < <10⁻³⁰), as predicted. Because genealogies that contain polymorphic mobile elements are old, they are shaped largely by the forces of ancient population history and are insensitive to recent demographic events, such as bottlenecks and expansions. Remarkably, the information in just two human DNA sequences provides substantial information about ancient human population size. By comparing the likelihood of various demographic models, we estimate that the effective population size of human ancestors living before 1.2 million years ago was 18,500, and we can reject all models where the ancient effective population size was larger than 26,000. This result implies an unusually small population for a species spread across the entire Old World, particularly in light of the effective population sizes of chimpanzees (21,000) and gorillas (25,000), which each inhabit only one part of a single continent.     

Independent origins of syringyl lignin in vascular plants

Lycophytes arose in the early Silurian ( approximately 400 Mya) and represent a major lineage of vascular plants that has evolved in parallel with the ferns, gymnosperms, and angiosperms. A hallmark of vascular plants is the presence of the phenolic lignin heteropolymer in xylem and other sclerified cell types. Although syringyl lignin is often considered to be restricted in angiosperms, it has been detected in lycophytes as well. Here we report the characterization of a cytochrome P450-dependent monooxygenase from the lycophyte Selaginella moellendorffii. Gene expression data, cross-species complementation experiments, and in vitro enzyme assays indicate that this P450 is a ferulic acid/coniferaldehyde/coniferyl alcohol 5-hydroxylase (F5H), and is capable of diverting guaiacyl-substituted intermediates into syringyl lignin biosynthesis. Phylogenetic analysis indicates that the Selaginella F5H represents a new family of plant P450s and suggests that it has evolved independently of angiosperm F5Hs.     

Shaping a bacterial genome by large chromosomal replacements, the evolutionary history of Streptococcus agalactiae

Bacterial populations are subject to complex processes of diversification that involve mutation and horizontal DNA transfer mediated by transformation, transduction, or conjugation. Tracing the evolutionary events leading to genetic changes allows us to infer the history of a microbe. Here, we combine experimental and in silico approaches to explore the forces that drive the genome dynamics of Streptococcus agalactiae, the leading cause of neonatal infections. We demonstrate that large DNA segments of up to 334 kb of the chromosome of S. agalactiae can be transferred through conjugation from multiple initiation sites. Consistently, a genome-wide map analysis of nucleotide polymorphisms among eight human isolates demonstrated that each chromosome is a mosaic of large chromosomal fragments from different ancestors suggesting that large DNA exchanges have contributed to the genome dynamics in the natural population. The analysis of the resulting genetic flux led us to propose a model for the evolutionary history of this species in which clonal complexes of clinical importance derived from a single clone that evolved by exchanging large chromosomal regions with more distantly related strains. The emergence of this clone could be linked to selective sweeps associated with the reduction of genetic diversity in three regions within a large panel of human isolates. Up to now sex in bacteria has been assumed to involve mainly small regions; our results define S. agalactiae as an alternative paradigm in the study of bacterial evolution.     

Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics

Many cancers have substantial genomic heterogeneity within a given tumor, and to fully understand that diversity requires the ability to perform single cell analysis. We performed targeted sequencing of a panel of single nucleotide variants (SNVs), deletions, and IgH sequences in 1,479 single tumor cells from six acute lymphoblastic leukemia (ALL) patients. By accurately segregating groups of cooccurring mutations into distinct clonal populations, we identified codominant clones in the majority of patients. Evaluation of intraclonal mutation patterns identified clone-specific punctuated cytosine mutagenesis events, showed that most structural variants are acquired before SNVs, determined that KRAS mutations occur late in disease development but are not sufficient for clonal dominance, and identified clones within the same patient that are arrested at varied stages in B-cell development. Taken together, these data order the sequence of genetic events that underlie childhood ALL and provide a framework for understanding the development of the disease at single-cell resolution.A more comprehensive understanding of how malignancies develop could facilitate the rational development of novel anticancer treatment and prevention strategies. Large projects that aim to comprehensively characterize somatic mutations in cancer samples have cataloged many of the recurrent genomic lesions in a wide variety of tumors (1). However, these studies do not measure the correlated cooccurrence of genomic lesions between different cells, which is required for understanding the clonal structure of a tumor as well as for rigorously determining temporal ordering of mutation acquisition. Other studies have provided some temporal resolution of mutation segregation patterns from diagnosis to disease recurrence, allowing for post hoc inference of intratumor clonal heterogeneity at diagnosis (2–5). However, approaches that rely on mutant allele frequencies to determine clonal structure require multiple samples from the same patient and are unable to resolve clones with mutations present at similar frequencies, which is a prerequisite to unambiguously determine the clonal structure and delineate the evolution of the disease (3–5). In principle, single cell genomics provides the most rigorous method to determine the clonal heterogeneity of tumors; as discussed below, there have been recent advances in this approach, but technical limitations have until now prevented it from fully addressing the questions of interest.Studies of pediatric acute lymphoblastic leukemias (ALL) have provided a limited ordering of the genetic events that underlie childhood leukemogenesis by studying prediagnostic samples. For example, ETV6 -RUNX1 translocations, which occur in about a third of patients under 10 y of age, have been shown to occur in utero by tracking the translocation back to neonatal blood spots (6, 7). In addition, a recent report suggests that ETV6-RUNX1 translocations stall B-cell development so that subsequent recombination-activating gene (RAG)–mediated genomic rearrangements become drivers of the creation of polyclonal structures (8). Furthermore, all of the ALL samples evaluated in this large study had acquired single nucleotide variants (SNVs) during disease progression, suggesting ETV6-RUNX1 translocations and the genomic structural variation in those cells are not sufficient for leukemogenesis (7, 8). However, the order in which each of these mutations are acquired and actual clonal structure of childhood ALL at diagnosis are unknown. It is therefore of paramount interest to develop a detailed understanding of patient-specific tumor clonal structure and evolutionary history both for fundamental understanding of the pathogenesis of childhood ALL, as well as for the design of new therapeutic and prevention strategies.     

From the Cover: PNAS Plus: Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments

Yakutia, Sakha Republic, in the Siberian Far East, represents one of the coldest places on Earth, with winter record temperatures dropping below −70 °C. Nevertheless, Yakutian horses survive all year round in the open air due to striking phenotypic adaptations, including compact body conformations, extremely hairy winter coats, and acute seasonal differences in metabolic activities. The evolutionary origins of Yakutian horses and the genetic basis of their adaptations remain, however, contentious. Here, we present the complete genomes of nine present-day Yakutian horses and two ancient specimens dating from the early 19th century and ∼5,200 y ago. By comparing these genomes with the genomes of two Late Pleistocene, 27 domesticated, and three wild Przewalski’s horses, we find that contemporary Yakutian horses do not descend from the native horses that populated the region until the mid-Holocene, but were most likely introduced following the migration of the Yakut people a few centuries ago. Thus, they represent one of the fastest cases of adaptation to the extreme temperatures of the Arctic. We find cis-regulatory mutations to have contributed more than nonsynonymous changes to their adaptation, likely due to the comparatively limited standing variation within gene bodies at the time the population was founded. Genes involved in hair development, body size, and metabolic and hormone signaling pathways represent an essential part of the Yakutian horse adaptive genetic toolkit. Finally, we find evidence for convergent evolution with native human populations and woolly mammoths, suggesting that only a few evolutionary strategies are compatible with survival in extremely cold environments.Yakutia (Sakha Republic, Russian Federation) is the coldest country in the whole Northern Hemisphere, showing annual thermal amplitudes over 100 °C and its entire range covered by permafrost (1). Despite such extreme conditions, a group of Turkic-speaking horse-riders, likely originating from the Altai-Sayan and/or Baïkal area, migrated into this region between the 13th and 15th centuries, pressed by the expansion of Mongolic tribes (2–4). The Yakut people successfully developed a unique economy based on horse and cattle breeding, with Yakutian horses mostly exploited as sources of meat and milk.The Yakutian horse is the most northerly distributed horse on the planet and certainly the most resistant to cold. In contrast to cattle, which are kept in stables during winter, horses live in the open air all year round, grazing on vegetation that is buried under deep snow cover for 7–8 mo (5). Yakutian horses exhibit unique morphoanatomical adaptations to the subarctic climate, being extraordinarily hairy and, as predicted by Allen’s rule, compactly built, with short limbs. Their metabolic needs are in phase with seasonal conditions, because they accumulate important fat reserves during the extremely brief period of vegetation growth and lower their activities during winter (6). Yakutian horses also show an increased carbohydrate metabolism in the spring, likely supporting higher energy expenditure and fetal growth (7).The evolutionary origins of Yakutian horses, however, still remain contentious. The most commonly accepted hypothesis proposes that they descend from a founding population brought by the Yakut people (2, 4). Some authors have suggested that at the time of their arrival, founding horses admixed with local populations descending from wild Late Pleistocene horses (8–10). In contrast, others have proposed that modern Yakutian horses exclusively originate from native Late Pleistocene populations, and were secondarily domesticated by the Yakut people upon their arrival (11).To date, the genomic diversity of Yakutian horses is mostly unknown, and genetic analyses are limited to few microsatellites and mtDNA sequences (12–14). In this study, we have sequenced and analyzed the complete genomes of 11 Yakutian horses, including nine present-day horses and two ancient specimens that lived in the region ∼5,200 y ago and in the early 19th century. The results revealed a genetic discontinuity between the Pleistocene and mid-Holocene genomic landscapes, showing that the contemporary population fully descends from a stock of domesticated horses. Taken together, these findings support the predominant hypothesis that the Yakut people introduced the breed in the 13th–15th centuries, and implies that the unique genetic adaptations of Yakutian horses, which we reveal here for the first time to our knowledge, were selected on an extremely short evolutionary time scale.     

Gain and loss of multiple functionally related, horizontally transferred genes in the reduced genomes of two microsporidian parasites

Microsporidia of the genus Encephalitozoon are widespread pathogens of animals that harbor the smallest known nuclear genomes. Complete sequences from Encephalitozoon intestinalis (2.3 Mbp) and Encephalitozoon cuniculi (2.9 Mbp) revealed massive gene losses and reduction of intergenic regions as factors leading to their drastically reduced genome size. However, microsporidian genomes also have gained genes through horizontal gene transfers (HGT), a process that could allow the parasites to exploit their hosts more fully. Here, we describe the complete sequences of two intermediate-sized genomes (2.5 Mbp), from Encephalitozoon hellem and Encephalitozoon romaleae. Overall, the E. hellem and E. romaleae genomes are strikingly similar to those of Encephalitozoon cuniculi and Encephalitozoon intestinalis in both form and content. However, in addition to the expected expansions and contractions of known gene families in subtelomeric regions, both species also were found to harbor a number of protein-coding genes that are not found in any other microsporidian. All these genes are functionally related to the metabolism of folate and purines but appear to have originated by several independent HGT events from different eukaryotic and prokaryotic donors. Surprisingly, the genes are all intact in E. hellem, but in E. romaleae those involved in de novo synthesis of folate are all pseudogenes. Overall, these data suggest that a recent common ancestor of E. hellem and E. romaleae assembled a complete metabolic pathway from multiple independent HGT events and that one descendent already is dispensing with much of this new functionality, highlighting the transient nature of transferred genes.     

From the Cover: Current perspectives and the future of domestication studies

It is difficult to overstate the cultural and biological impacts that the domestication of plants and animals has had on our species. Fundamental questions regarding where, when, and how many times domestication took place have been of primary interest within a wide range of academic disciplines. Within the last two decades, the advent of new archaeological and genetic techniques has revolutionized our understanding of the pattern and process of domestication and agricultural origins that led to our modern way of life. In the spring of 2011, 25 scholars with a central interest in domestication representing the fields of genetics, archaeobotany, zooarchaeology, geoarchaeology, and archaeology met at the National Evolutionary Synthesis Center to discuss recent domestication research progress and identify challenges for the future. In this introduction to the resulting Special Feature, we present the state of the art in the field by discussing what is known about the spatial and temporal patterns of domestication, and controversies surrounding the speed, intentionality, and evolutionary aspects of the domestication process. We then highlight three key challenges for future research. We conclude by arguing that although recent progress has been impressive, the next decade will yield even more substantial insights not only into how domestication took place, but also when and where it did, and where and why it did not.     

Evolution of stickleback in 50 years on earthquake-uplifted islands

How rapidly can animal populations in the wild evolve when faced with sudden environmental shifts? Uplift during the 1964 Great Alaska Earthquake abruptly created freshwater ponds on multiple islands in Prince William Sound and the Gulf of Alaska. In the short time since the earthquake, the phenotypes of resident freshwater threespine stickleback fish on at least three of these islands have changed dramatically from their oceanic ancestors. To test the hypothesis that these freshwater populations were derived from oceanic ancestors only 50 y ago, we generated over 130,000 single-nucleotide polymorphism genotypes from more than 1,000 individuals using restriction site-associated DNA sequencing (RAD-seq). Population genomic analyses of these data support the hypothesis of recent and repeated, independent colonization of freshwater habitats by oceanic ancestors. We find evidence of recurrent gene flow between oceanic and freshwater ecotypes where they co-occur. Our data implicate natural selection in phenotypic diversification and support the hypothesis that the metapopulation organization of this species helps maintain a large pool of genetic variation that can be redeployed rapidly when oceanic stickleback colonize freshwater environments. We find that the freshwater populations, despite population genetic analyses clearly supporting their young age, have diverged phenotypically from oceanic ancestors to nearly the same extent as populations that were likely founded thousands of years ago. Our results support the intriguing hypothesis that most stickleback evolution in fresh water occurs within the first few decades after invasion of a novel environment.On March 27, 1964, the largest earthquake ever recorded in North America struck the south coast of Alaska (1, 2). This catastrophic event uplifted islands in Prince William Sound and the Gulf of Alaska in just a few minutes, creating ponds from formerly marine habitat and setting the stage for the diversification of threespine stickleback fish (Gasterosteus aculeatus) in these new freshwater sites. This seismic disturbance provides an excellent opportunity to address long-standing evolutionary questions regarding how often dramatic phenotypic shifts can happen over contemporary timescales (3–7).Despite examples of rapid divergence in wild populations, evolutionary rates may often be constrained by a suite of factors (8). For example, evolution in new habitats may be limited by waiting times for new beneficial mutations (9–11). Even when adaptation occurs from standing genetic variation, evolution via selection of numerous independent loci of small effect may be time consuming (12–16). We know, however, that evolution can occur rapidly, particularly under artificial selection or in human-altered landscapes (17–21). In addition, empirical studies in the wild—particularly in response to significant environmental changes—have demonstrated that strong selection and rapid evolution over decades may be more common than once thought (22–24).A rapid evolutionary response is predicted when the intensity of directional selection is strong (11, 25), a scenario likely to occur immediately after a habitat shift or environmental disturbance (26, 27). However, because of previous technological limitations, few studies of rapid differentiation in the wild have included genetic data to fully disentangle evolution from induced phenotypic plasticity. The small numbers of markers previously available for most population genetic studies have not provided the necessary precision with which to analyze very recently diverged populations (but see refs. 28 and 29). As a consequence, the frequency of contemporary evolution in the wild is still poorly defined, and its genetic and genomic basis remains unclear (30).Advances in sequencing technology now allow the precise inference from genomic data of colonization history and evolutionary patterns that have occurred over just a few generations (31, 32). The threespine stickleback system is ideal for testing hypotheses about contemporary evolution. Postglacial adaptive radiations over the last 12,000–20,000 y in newly available freshwater habitats have spawned divergent phenotypes that demonstrate parallel phenotypic evolution (33, 34), with underlying parallel genetic (35–39) and genomic (40–43) bases. An open question, however, is whether this parallel divergence in stickleback actually requires thousands of years, or whether it can occur in nature over decadal timescales, as is implied by studies of a small number of recently formed artificial and wild stickleback populations (44–50). Also unknown is how often the countless populations of stickleback in geographically close ponds represent invasion followed by local dispersal or independent founding from the sea.To address these questions, we identified populations from three islands (Middleton, Montague, and Danger) in Prince William Sound and the Gulf of Alaska that could have been founded only after the 1964 earthquake (Fig. 1 and SI Appendix, Table S1). Middleton Island was uplifted 3.4 m, creating a new terrace with ponds from a previously submarine platform (1). Similarly, Danger and Montague Islands experienced uplift and creation of new ponds (51). Stickleback now can be found in many of the habitats produced by the earthquake (52). We first analyzed a subset of populations from Middleton Island to describe the pattern of multivariate phenotypic divergence. We then produced and analyzed restriction site-associated DNA sequencing (RAD-seq) data (53, 54) from 25,000 RAD loci in 1,057 individuals collected from a total of 20 populations from all three islands and one mainland population. Deep sequencing yielded a set of 130,000 single-nucleotide polymorphisms (SNPs) and a total of 146 million genotypes. This large genomic dataset allowed us to ask whether phenotypic and genetic divergence in stickleback, thought to require thousands of years, can occur in a fraction of that time. Unlike previous studies that have made inroads into this question (47–50), the high level of biological replication of individually genotyped samples, within and across populations, in the present study avails a battery of population genomic analyses such as analysis of molecular variance (AMOVA), principal component analysis (PCA), and STRUCTURE. These approaches are most appropriate for defining (and assigning individuals to) genetic groupings across recently formed populations potentially still experiencing gene flow, such as those that are the focus of our study. We use this robust dataset to test the parallel origin of several populations against a precisely dated geological event—the Great Alaskan Earthquake of 1964—to ask whether replicated colonization of a large number of newly formed freshwater habitats by oceanic stickleback ancestors occurred independently on different islands and even amid close geographic locales within individual islands.Open in a separate windowFig. 1.Sampling locations. (A) Prince William Sound and the Gulf of Alaska, with Danger (B), Montague (C), and Middleton (D) Islands boxed. (Inset) Alaska with box representing sampling area. Sites are coded by whether they are freshwater or oceanic habitat and by the dominant ecotype found in the population. Dark gray shading within each island cartoon delineates the approximate pre-1964 shoreline.     

Genomic stability through time despite decades of exploitation in cod on both sides of the Atlantic

The mode and extent of rapid evolution and genomic change in response to human harvesting are key conservation issues. Although experiments and models have shown a high potential for both genetic and phenotypic change in response to fishing, empirical examples of genetic responses in wild populations are rare. Here, we compare whole-genome sequence data of Atlantic cod (Gadus morhua) that were collected before (early 20th century) and after (early 21st century) periods of intensive exploitation and rapid decline in the age of maturation from two geographically distinct populations in Newfoundland, Canada, and the northeast Arctic, Norway. Our temporal, genome-wide analyses of 346,290 loci show no substantial loss of genetic diversity and high effective population sizes. Moreover, we do not find distinct signals of strong selective sweeps anywhere in the genome, although we cannot rule out the possibility of highly polygenic evolution. Our observations suggest that phenotypic change in these populations is not constrained by irreversible loss of genomic variation and thus imply that former traits could be reestablished with demographic recovery.

As anthropogenic activities rapidly transform the environment, a fundamental question is whether wild populations have the capacity to adapt and evolve fast enough in response (1–3). Phenotypic change can result from phenotypic plasticity, but emerging examples of genomic change over only a few generations have made clear that rapid evolution is also possible (4–6). In the literature, one of the most dramatic and widely cited cases involves the declining age and size at maturation of Atlantic cod (Gadus morhua) following several generations of high fishing pressure (3, 7–10). Fisheries produce some of the fastest rates of phenotypic change ever observed in wild populations (2, 11), but the extent to which fisheries-induced evolution has occurred in the wild and the degree to which it is reversible remain strongly debated (12).The hypothesis that evolution underlies these phenotypic changes is supported by a range of observations. For example, theory on the selective nature of many fisheries reveals that higher rates of harvesting will—with only a few exceptions—favor earlier sexual maturation, greater investment in reproduction, and slower growth (13). In addition, experiments in the laboratory that selectively remove large or small individuals from a population reveal rapid evolution of body size and maturation time in only a few generations, as well as substantial impacts on fishery yields (14–16). Fisheries-induced evolution experiments in the laboratory also reveal selective sweeps through dramatic shifts in allele frequencies, loss of genetic diversity, and increases in linkage disequilibrium at specific locations in the genome (15, 17, 18).However, translating these findings to wild populations has been substantially more difficult. One concern is that phenotypic plasticity, gene flow, or spatial shifts in populations can also explain the substantial phenotypic and limited genotypic changes reported from the wild to date (10, 13, 19–23). The magnitude and rate of fisheries-induced evolution may also be quite small in the wild (19). While theory provides strong evidence that fishing can be a potent driver of evolutionary changes, a clear empirical demonstration of fisheries-induced evolution would require evidence that the observed change is genetic (13). Whether and to what extent the widespread genomic reorganization observed in experiments also occurs in wild-harvested populations therefore remain unknown.Genomic analyses of temporal samples before and after selective events have provided key opportunities to test for rapid adaptive evolution from standing genetic variation in wild populations by identifying unusually strong shifts in allele frequencies over time (4, 5). In addition, the history of genomic research with Atlantic cod (24, 25) provides a unique opportunity to test for genomic signatures of fisheries-induced evolution in particular. Archival samples collected by fisheries scientists decades or even centuries ago represent a valuable source of historical genomic material that can provide rare insight into the genetic patterns of the past (26). Here, we obtained whole-genome sequence data from well-preserved archives of Atlantic cod scales and otoliths (ear bones) that were originally collected from two populations on either side of the Atlantic Ocean: the northeast Arctic population sampled near Lofoten, Norway in 1907 and the Canadian northern cod population sampled near Twillingate, Newfoundland in 1940 (Fig. 1A and SI Appendix, Table S1). The Canadian northern population collapsed from overfishing in the early 1990s, while the northeast Arctic population experienced high fishing rates but smaller declines in biomass (10, 27, 28). Both populations have shown marked reductions in age at maturation, though with slight increases in maturation age in northeast Arctic cod after 2005 (Fig. 1B). We compared these historical genomes with modern data from the same locations (Fig. 1A and SI Appendix, Table S2). In total, we analyzed 113 individual genomes (Methods) from these two unique populations that had independently experienced intensive fishing during the last century (7, 10). We found a marked lack of large genomic changes or selective sweeps through time, suggesting instead that phenotypic plasticity or, potentially, highly polygenic evolution can explain the observed changes in phenotype.Open in a separate windowFig. 1.Spatiotemporal population structure based on genome-wide data in Atlantic cod. (A) In total, 113 modern and historical specimens were analyzed from northern cod collected in Newfoundland, Canada (1940, yellow; 2013, dark yellow) and from northeast Arctic cod collected in the Lofoten archipelago, Norway (1907, orange; modern: 2011, red; 2014, dark red). (B) Age at 50% maturity over time in each population. (C) PCA as implemented in PCAngsd. Velicier’s minimum average partial (MAP) test identified a single significant PC and only one PC is shown. Individuals are colored according to A. (D) Model-based ADMIXTURE ancestry components for historical (1907, 1940) and modern (2013, 2014) populations (k = 2; NGSadmix). Each individual is represented by a column colored to show the proportion of each ancestry component for Canada (dark yellow) and Norway (orange). Population differentiation based on pairwise weighted F_ST is also shown. (E) The correlation between the allele frequencies in historical and modern populations. Colors reflect the relative density of points, from darker (more density) to lighter (less density). R², coefficient of correlation.     

On the origins of hierarchy in complex networks

Hierarchy seems to pervade complexity in both living and artificial systems. Despite its relevance, no general theory that captures all features of hierarchy and its origins has been proposed yet. Here we present a formal approach resulting from the convergence of theoretical morphology and network theory that allows constructing a 3D morphospace of hierarchies and hence comparing the hierarchical organization of ecological, cellular, technological, and social networks. Embedded within large voids in the morphospace of all possible hierarchies, four major groups are identified. Two of them match the expected from random networks with similar connectivity, thus suggesting that nonadaptive factors are at work. Ecological and gene networks define the other two, indicating that their topological order is the result of functional constraints. These results are consistent with an exploration of the morphospace, using in silico evolved networks.     

African great apes are natural hosts of multiple related malaria species,including Plasmodium falciparum

Plasmodium reichenowi, a chimpanzee parasite, was until very recently the only known close relative of Plasmodium falciparum, the most virulent agent of human malaria. Recently, Plasmodium gaboni, another closely related chimpanzee parasite, was discovered, suggesting that the diversity of Plasmodium circulating in great apes in Africa might have been underestimated. It was also recently shown that P. reichenowi is a geographically widespread and genetically diverse chimpanzee parasite and that the world diversity of P. falciparum is fully included within the much broader genetic diversity of P. reichenowi. The evidence indicates that all extant populations of P. falciparum originated from P. reichenowi, likely by a single transfer from chimpanzees. In this work, we have studied the diversity of Plasmodium species infecting chimpanzees and gorillas in Central Africa (Cameroon and Gabon) from both wild-living and captive animals. The studies in wild apes used noninvasive sampling methods. We confirm the presence of P. reichenowi and P. gaboni in wild chimpanzees. Moreover, our results reveal the existence of an unexpected genetic diversity of Plasmodium lineages circulating in gorillas. We show that gorillas are naturally infected by two related lineages of parasites that have not been described previously, herein referred to as Plasmodium GorA and P. GorB, but also by P. falciparum, a species previously considered as strictly human specific. The continuously increasing contacts between humans and primate populations raise concerns about further reciprocal host transfers of these pathogens.     

Ecological diversification reveals routes of pathogen emergence in endemic Vibrio vulnificus populations

Pathogen emergence is a complex phenomenon that, despite its public health relevance, remains poorly understood. Vibrio vulnificus, an emergent human pathogen, can cause a deadly septicaemia with over 50% mortality rate. To date, the ecological drivers that lead to the emergence of clinical strains and the unique genetic traits that allow these clones to colonize the human host remain mostly unknown. We recently surveyed a large estuary in eastern Florida, where outbreaks of the disease frequently occur, and found endemic populations of the bacterium. We established two sampling sites and observed strong correlations between location and pathogenic potential. One site is significantly enriched with strains that belong to one phylogenomic cluster (C1) in which the majority of clinical strains belong. Interestingly, strains isolated from this site exhibit phenotypic traits associated with clinical outcomes, whereas strains from the second site belong to a cluster that rarely causes disease in humans (C2). Analyses of C1 genomes indicate unique genetic markers in the form of clinical-associated alleles with a potential role in virulence. Finally, metagenomic and physicochemical analyses of the sampling sites indicate that this marked cluster distribution and genetic traits are strongly associated with distinct biotic and abiotic factors (e.g., salinity, nutrients, or biodiversity), revealing how ecosystems generate selective pressures that facilitate the emergence of specific strains with pathogenic potential in a population. This knowledge can be applied to assess the risk of pathogen emergence from environmental sources and integrated toward the development of novel strategies for the prevention of future outbreaks.

The emergence of human pathogens is one of the most concerning public health topics of modern times (1–4). According to the World Health Organization, over 300 emerging infectious diseases have been reported in the 1940 to 2004 period, a trend that has continued steadily with recent outbreaks of Ebola in West Africa, Cholera in Yemen, and the global pandemic caused by COVID-19 (3–5). Even though classical molecular approaches have advanced our understanding of bacterial pathogenesis, to date, the genetic adaptations and ecological drivers that facilitate selected strains within a species to emerge as pathogens and successfully colonize the human host remain poorly understood. Given the magnitude and complexity of this urgent threat, it is critical to develop tractable organismal model systems and theoretical frameworks that allow us to dissect the molecular adaptations and environmental factors that lead to the emergence of such human pathogens.Vibrio vulnificus, an emergent human pathogen, is one of the leading causes of non-Cholera, Vibrio-associated deaths globally (6). Despite being a natural inhabitant of estuarine, coastal, and brackish waters (7), this flesh-eating bacterium has gained particular notoriety as one of the fastest killing pathogens (8, 9). Humans are typically infected with V. vulnificus through ingestion of contaminated raw seafood or by direct exposure of open wounds to seawater (6). V. vulnificus infections often result in fulminant septicaemia with an alarming mortality rate exceeding 50% (6, 10–13). The bacterium is particularly lethal in some susceptible hosts, such as immunocompromised patients or those with alcohol-associated liver cirrhosis, diabetes mellitus, or hemochromatosis (14). The annual case counts of V. vulnificus infections have steadily increased over the past 20 y in the United States (15). An upsurge in its worldwide distribution over the past three decades, in correlation with climate change, has led to disease outbreaks in regions with no history of V. vulnificus infections (16–18). Furthermore, models predict this trend to continue resulting in a steady expansion of its geographical range and the subsequent increased risk of human infections (16, 19–21).Based on a series of biochemical and phenotypic traits, V. vulnificus strains have been historically classified into three Biotypes (BT): BT1, which is mostly associated with human infections (22, 23), BT2, which is primarily pathogenic to eels (24, 25), and BT3, which is geographically restricted to Israel and possesses hybrid characteristics from BT1 and BT2 (26, 27). In contrast to Vibrio cholerae, in which all strains capable of causing cholera belong to a single clade, genomic comparisons of V. vulnificus reveal a more complex pattern in the distribution of its clinical strains (28–30). Phylogenomic analyses indicate that the population of V. vulnificus is composed of four distinct groups or clusters (Cluster 1 to 4), which largely overlap with the classical BT classification system (23, 26, 28, 31, 32). Our analyses indicate that the two largest clusters, C1 and C2, exhibit high genomic divergence and appear to be speciating (28), with clinical strains from BT1 predominantly belonging to C1 (22, 23), whereas strains from C2 are primarily associated with BT2 (6, 24, 25). C3 is highly clonal and fully overlaps with BT3, and the rare C4 contains only four nonclonal strains and belongs to BT1 (28, 31). Interestingly, despite patients showing conserved clinical symptoms, C1 clinical strains arise from different clades within the cluster, suggesting independent emergence events of this deadly pathogen (28, 31, 32). To date, the unique genetic traits that allow certain C1 strains to cause severe septicemia remain mostly unknown, posing a daunting public health risk as it hinders our ability to detect potentially pathogenic V. vulnificus (33).Recently, using a combination of bioinformatic and phenotypic analyses that surveyed more than 100 strains of V. vulnificus, we determined that V. vulnificus C1 appears to be associated with a unique ecological lifestyle or ecotype (28). Nonetheless, to date, the ecological drivers that lead to the emergence of clinical V. vulnificus C1 and their pathogenic traits remain poorly understood. In order to start untangling the complex in-situ interactions between genotypes and the environment that underlie the emergence of clinical strains, in this study, we recently surveyed a large estuary in eastern Florida, the Indian River Lagoon (IRL), where outbreaks of the disease frequently occur (7, 34). We found endemic populations of V. vulnificus in the estuary and established two sampling locations to study the environmental dynamics of this bacterium in several natural reservoirs such as water, sediment, oysters, and cyanobacteria. Interestingly, the two sampling sites show major differences in the distribution of V. vulnificus clusters. One of them, Feller’s house (Site A), appears to be significantly enriched with C1 strains, whereas in the second sampling site, Shepard Park (Site B), we mostly recovered strains from C2. Genomic analyses of these strains indicate that, despite these major differences in distribution, high recombination rates as well as frequent exchange of mobile genetic elements and virulence factors between these V. vulnificus populations occur. Microdiversity analyses of these genomes revealed unique genomic markers among C1 strains in the form of clinical-associated alleles (CAAs) with a potential direct role in virulence. The isolated V. vulnificus strains are resistant to numerous commonly used antibiotics irrespective of cluster or site of isolation. However, phenotypic analyses indicate that strains from Site A exhibit traits associated with clinical outcomes, including the ability to resist serum and catabolize sialic acid, unlike those from Site B. Finally, metagenomic and physicochemical analyses of the sampling sites indicate that this marked cluster distribution is strongly associated with distinct biotic and abiotic factors (e.g., salinity, nutrients, or biodiversity) revealing how ecosystems might generate selective pressures that facilitate the emergence of specific strains in a population with pathogenic potential.     

Whole-genome nucleotide diversity, recombination, and linkage disequilibrium in the model legume Medicago truncatula

Medicago truncatula is a model for investigating legume genetics, including the genetics and evolution of legume-rhizobia symbiosis. We used whole-genome sequence data to identify and characterize sequence polymorphisms and linkage disequilibrium (LD) in a diverse collection of 26 M. truncatula accessions. Our analyses reveal that M. truncatula harbors both higher diversity and less LD than soybean (Glycine max) and exhibits patterns of LD and recombination similar to Arabidopsis thaliana. The population-scaled recombination rate is approximately one-third of the mutation rate, consistent with expectations for a species with a high selfing rate. Linkage disequilibrium, however, is not extensive, and therefore, the low recombination rate is likely not a major constraint to adaptation. Nucleotide diversity in 100-kb windows was negatively correlated with gene density, which is expected if diversity is shaped by selection acting against slightly deleterious mutations. Among putative coding regions, members of four gene families harbor significantly higher diversity than the genome-wide average. Three of these families are involved in resistance against pathogens; one of these families, the nodule-specific, cysteine-rich gene family, is specific to the galegoid legumes and is involved in control of rhizobial differentiation. The more than 3 million SNPs that we detected, approximately one-half of which are present in more than one accession, are a valuable resource for genome-wide association mapping of genes responsible for phenotypic diversity in legumes, especially traits associated with symbiosis and nodulation.     

Climate change, adaptive cycles, and the persistence of foraging economies during the late Pleistocene/Holocene transition in the Levant

Climatic forcing during the Younger Dryas (～12.9-11.5 ky B.P.) event has become the theoretical basis to explain the origins of agricultural lifestyles in the Levant by suggesting a failure of foraging societies to adjust. This explanation however, does not fit the scarcity of data for predomestication cultivation in the Natufian Period. The resilience of Younger Dryas foragers is better illustrated by a concept of adaptive cycles within a theory of adaptive change (resilience theory). Such cycles consist of four phases: release/collapse (Ω); reorganization (α), when the system restructures itself after a catastrophic stimulus through innovation and social memory--a period of greater resilience and less vulnerability; exploitation (r); and conservation (K), representing an increasingly rigid system that loses flexibility to change. The Kebarans and Late Natufians had similar responses to cold and dry conditions vs. Early Natufians and the Pre-Pottery Neolithic A responses to warm and wet climates. Kebarans and Late Natufians (α-phase) shifted to a broader-based diet and increased their mobility. Early Natufian and Pre-Pottery Neolithic A populations (r- and K-phases) had a growing investment in more narrowly focused, high-yield plant resources, but they maintained the broad range of hunted animals because of increased sedentism. These human adaptive cycles interlocked with plant and animal cycles. Forest and grassland vegetation responded to late Pleistocene and early Holocene climatic fluctuations, but prey animal cycles reflected the impact of human hunting pressure. The combination of these three adaptive cycles results in a model of human adaptation, showing potential for great sustainability of Levantine foraging systems even under adverse climatic conditions.     

From the Cover: INAUGURAL ARTICLE by a Recently Elected Academy Member:A comparison of worldwide phonemic and genetic variation in human populations

Worldwide patterns of genetic variation are driven by human demographic history. Here, we test whether this demographic history has left similar signatures on phonemes—sound units that distinguish meaning between words in languages—to those it has left on genes. We analyze, jointly and in parallel, phoneme inventories from 2,082 worldwide languages and microsatellite polymorphisms from 246 worldwide populations. On a global scale, both genetic distance and phonemic distance between populations are significantly correlated with geographic distance. Geographically close language pairs share significantly more phonemes than distant language pairs, whether or not the languages are closely related. The regional geographic axes of greatest phonemic differentiation correspond to axes of genetic differentiation, suggesting that there is a relationship between human dispersal and linguistic variation. However, the geographic distribution of phoneme inventory sizes does not follow the predictions of a serial founder effect during human expansion out of Africa. Furthermore, although geographically isolated populations lose genetic diversity via genetic drift, phonemes are not subject to drift in the same way: within a given geographic radius, languages that are relatively isolated exhibit more variance in number of phonemes than languages with many neighbors. This finding suggests that relatively isolated languages are more susceptible to phonemic change than languages with many neighbors. Within a language family, phoneme evolution along genetic, geographic, or cognate-based linguistic trees predicts similar ancestral phoneme states to those predicted from ancient sources. More genetic sampling could further elucidate the relative roles of vertical and horizontal transmission in phoneme evolution.Both languages and genes experience descent with modification, and both are affected by evolutionary processes such as migration, population divergence, and drift. Thus, although languages and genes are transmitted differently, combining linguistic and genetic analyses is a natural approach to studying human evolution (1, 2). Cavalli-Sforza et al. (3) juxtaposed a genetic phylogeny with linguistic phyla proposed by Greenberg (described in ref. 4) and observed qualitative concordance; however, their comparison of linguistic and genetic variation was not quantitative. A later analysis of genetic polymorphisms and language boundaries suggested a causal role for language in restricting gene flow in Europe (5). More recently, population-level genetic data have been compared with patterns expected from language family classifications (2, 6–12). Other studies addressed whether the serial founder effect model from genetics—human expansion from an origin in Africa, followed by serial contractions in effective population size during the peopling of the world (13, 14)—explains various linguistic patterns (15–19).Past studies are generally asymmetrical in their approaches to the comparison of genes and languages: some focus on genetic analysis and use linguistics to interpret results, and others analyze linguistic data in light of genetic models. Our study directly compares the signatures of human demographic history in microsatellite polymorphisms from 246 worldwide populations (20) and complete sets of phonemes (phoneme inventories) for 2,082 languages; these are the largest available datasets of both genotyped populations and phonemes, the smallest units of sound that can distinguish meaning between words. Languages do not hold information about deep ancestry as genes do, and phoneme evolution is complex: phonemes can be transmitted vertically from parents to offspring or horizontally between speakers of different languages, and phonemes can change over time within a language (21–23). We compare the geographic and historical patterns evident in phonemes and genes to determine the traces of human history in each data type.Phonemic data were compiled by M.R. (the Ruhlen database); for 2,082 languages with complete phoneme inventories and referenced sources in this database, we annotated each language with geographic coordinates (Fig. 1A) and the number of speakers reported (24). We also analyzed PHOIBLE (PHOnetics Information Base and Lexicon) (25), a linguistic database with phoneme inventories for 968 languages. For 139 globally distributed populations in the Ruhlen database (114 in PHOIBLE), we matched each population’s genetic data to the phoneme inventory of its native language (20), producing novel “phoneme–genome datasets” that allow joint analysis of genes and languages.Open in a separate windowFig. 1.Procrustes-transformed PCs for all phonemes and regional axes of phonemic and genetic differentiation. (A) Locations of 2,082 languages in the Ruhlen database. Phoneme inventory size of each language is indicated by the color bar. We performed Procrustes analyses to compare the first two PCs of phonemic data (B and C) and genetic data (D) to the geographic locations of languages/populations (P < 10⁻⁵ for all three comparisons after 100,000 permutations). The mean Procrustes-transformed PC values (B) for phonemes in the Ruhlen database (t₀ = 0.57), (C) for phonemes in PHOIBLE (t₀ = 0.52), and (D) for allele frequencies (t₀ = 0.69) are displayed in each geographic region. Circle size corresponds to number of languages (B and C) or populations (D). (E) For the Ruhlen phoneme–genome dataset, pairwise geographic distance matrices were projected along different axes (calculated at 1° intervals); within each region, the rotated axis of geographic distance that was most strongly associated (greatest Mantel r) with phonemic distance (black arrows) and genetic distance (gray dashed arrows) is shown. Thinner arrows (Europe, East Asia, South America) indicate nonsignificant associations. Black dots indicate population locations for the Ruhlen phoneme–genome dataset. With the exception of North America, axes of phonemic differentiation and genetic differentiation are similar in most regions (North America: 78° difference; other regions: mean difference 16°).To compare the signatures of human demographic history on genetic variation and phoneme inventories, we used Procrustes analyses to compare principal components (PCs) for both data types with sample geographic locations and determined whether phonemic and genetic distance are more correlated than expected from geographic distance alone. We also developed a new method for identifying regional axes of linguistic and genetic differentiation and tested whether the origin of the human expansion out of Africa can be detected from the geographic distribution of the numbers of phonemes in languages (phoneme inventory sizes). Conflicting predictions exist for the effects of geographic isolation and population contact on language evolution (e.g., refs. 26–29); we tested these by comparing phoneme inventories according to language density at varying radii. We also quantified the extent to which phoneme evolution can be modeled along genetic, geographic, and cognate-based phylogenies. With these joint analyses, we tested whether phonemes and alleles carry signatures of ancient population divergence and recent human migrations, and we identified demographic processes that have different effects on phonemes and alleles.