Plecotus austriacus. Glacial refugia predicted by palaeo-modelling match those identified from analyses of extant genetic diversity and model-based inference of demographic history. Former refugial populations currently contain disproportionately high genetic diversity, but niche conservatism, shifts in suitable areas and barriers to migration mean that these hotspots of genetic diversity are under threat from future climate change. Evidence of population decline despite recent northward migration highlights the need to conserve leading-edge populations for spearheading future range shifts.With rates of climate change exceeding the rate at which many species are able to shift their range or adapt, it is important to understand how future changes are likely to affect biodiversity at all levels of organisation. Understanding past responses and extent of niche conservatism in climatic tolerance can help predict future consequences. We use an integrated approach to determine the genetic consequences of past and future climate changes on a bat species,  Microsatellite library design, mtDNA primers, PCR reaction conditions, PCR cycle programs and microsatellite loci selection procedures are outlined in Appendix S1.Genomic DNA was extracted from all samples and amplified for one mitochondrial (mtDNA) gene  and one species of the same family  as outgroups to root the tree (Appendix S1). Parsimony haplotype networks for the Cyt b sequences were constructed using the program NETWORK . See Appendix S1 for analysis of mtDNA and microsatellite genetic diversity.We constructed Bayesian phylogenetic trees for the mtDNA region, using sequences of two congenerics  generations following a burn-in phase of 5 × 105 generations (Appendix S1).Individual-based Bayesian assignment tests implemented in STRUCTURE v2.3.3   ∼130,000BP] and future (2080) climatic conditions. Models were run at a resolution of approximately 5 km (2.5 arc min). The study extent was set as the whole of Europe including Mediterranean islands, because the Mediterranean Sea represents the southern limit of the species' distribution . After removing highly correlated variables (correlation coefficients ≥0.8) and variables that did not contribute to the ENMs, the following environmental variables were included in the models: mean temperature of the coldest quarter (BIO11), temperature annual range (BIO7), annual mean temperature (BIO1), annual precipitation (BIO12), slope, altitude, precipitation during the warmest quarter (BIO18) and mean temperature of the warmest quarter (BIO10).Climatic and topographic environmental layers were downloaded from World Clim  of the Receiver Operator Characteristics (Appendix S1).http://www.worldclim.org). Areas that were predicted to remain suitable across LIG, LGM and current conditions were assigned as potential glacial refugia.Models were projected into the past using the CCSM and MIRCO General Circulation Models (GCMs) for the LGM and one LIG model (WorldClim http://www.ccafs-climate.org/), using the A2 scenario (Appendix S1).Future projections for 2080 were performed with three GCMs: HadCM3, IPSL-CM4 and CCSM  using Species Accumulation Curves (Appendix S1), based on the approach outlined in Pfenninger et al. .P. austriacus using the ABC approach implemented in DIYABC v1.0.4  in population size .6 simulations for each scenario tested using the combined microsatellite and mtDNA data sets (Appendix S1 for model parameters). The posterior probability of scenarios was estimated using a weighted polychotomous logistic regression on the 1% of simulated data sets that were closest to the observed data set. Taking into account the criticism of ABC model choice outlined in Robert et al.  in P. austriacus identified 32 haplotypes across the species' range, 27 of which were confined to Iberian populations, which are located at the rear-edge-of-the range , referred to henceforth as the south-eastern and north-western clades. All samples from outside Iberia were nested within the south-eastern clade forming a subgroup with two eastern Iberian haplotypes located just south of the Pyrenees . At the microsatellite level, individual-based assignment tests detected genetic structure across the range of P. austriacus, dividing the samples into seven clusters , roughly corresponding to the six main geographical areas separated by mountains ranges or large expanses of water. Mainland Western European samples, though belonging primarily to the Balkan cluster, showed high levels of admixture  and the Balkans (0.23) into Western Europe and from Western Europe into England (0.17), while rates of gene flow in the opposite (southern) direction were very low (< 0.01). We found limited contemporary gene flow across the Pyrenees both in and out of Iberia, with the majority of Iberian bats remaining in Iberia in the last few generations .Bayesian estimations of contemporary gene flow rates among the six geographical populations (expressed as proportions of the population migrating into other regions in the last few generations) indicate a predominately north-western migration direction across the range of training = 0.943 ± 0.01, AUCtest = 0.9 ± 0.02). The primary environmental variables affecting habitat suitability for P. austriacus across its range were winter temperature, temperature range, annual temperature and annual rainfall. Palaeo-ENMs predicted that suitable climatic conditions for P. austriacus during the LGM occurred in Iberia, Italy and the Mediterranean coast of France and the Balkans, but highly suitable conditions (habitat suitability > 0.7) only existed along the east coast of Iberia .All models had high predictive ability and did not overfit presence data .A MESS analysis showed that climatic conditions in the whole of Iberia during the LGM had parallels to conditions found within the current range of P. austriacus, with suitable conditions restricted to northern parts of Iberia, areas north of the Alps and to the north-west of the Balkans  being located in unsuitable areas or small isolated patches of suitable habitats. Losses of genetic diversity are predicted to be particularly high in Iberia Fig. a. AccumuP. austriacus and the source population from which all other European populations emerged  relative to zero support for the bottleneck scenario and around 10% support for the no change in population size model . Error rates were estimated at 0.14 and 0.04 for type 1 and 2 errors respectively.P. austriacus, and that future climate change is likely to reshape these patterns resulting in extensive losses of genetic diversity and pose the greatest threat to former refugial populations with the highest genetic diversity. This pattern is likely to be common to many temperate European species that survived Pleistocene glaciation events in Mediterranean refugia.This study highlights the importance of combining a historic perspective with future predictions to understand the genetic consequences of climate change. We show that historic climate changes and geographical barriers played an important role in shaping patterns of genetic variation in P. austriacus and that all other populations emerged from the Iberian population, an inference supported by palaeo-modelling and the phylogenetic analysis. Evidence from the fossil record also supports the Iberian origin of P. austriacus, and suggests that it did not appear in central Europe before the mid-Holocene (Juste et al. P. austriacus existed in Iberia for at least 130 000 years, thus suggesting that Iberia represents a ‘stable rear-edge’ population (Hampe & Petit ABC demographic history inference indicates that Iberia was the main Pleistocene glacial refugium of et al. Iberia harbours substantially higher levels of mitochondrial and nuclear DNA diversity than the rest of the range and the greatest number of unique haplotypes and private alleles, a further testimony to the long-term stability of Iberian populations Hewitt . The peret al. P. austriacus. This may be due to the presence of a cryptic sister species, Plecotus kolombatovici, in the area (Juste et al. P. austriacus despite the predicted suitable conditions in Italy during the LIG and LGM and despite the presence of a unique Italian mtDNA haplotype and microsatellite cluster. Absence of sufficient samples from the Mediterranean coast of France meant that inference regarding the role of this potential refugium could only be made by including a ghost, unsampled population in the analysis.Despite being recognised as an important glacial refugium for most European bat species studied so far (e.g. Rebelo P. austriacus is likely to be conserved and therefore can be projected to estimate habitat suitability under future climate change (Cordellier & Pfenninger P. austriacus in Iberia during the LGM are similar to current conditions found across its range. Although niche conservatism in terms of tolerance to cold is not necessarily an indication of future tolerance to warming conditions, rates of future changes may be too fast for the climatic niche to evolve (Quintero & Wiens Concordance between the location of glacial refugia identified in this study through genetic analysis and ecological niche modelling indicates that the climatic niche of et al. P. austriacus (Norberg & Rayner A species' ability to respond to future climate change depends on intrinsic factors, including physiological sensitivity to changes, genetic adaptive capacity and dispersal ability, the latter being affected by extrinsic factors such as geographical barriers (Dawson et al. P. austriacus. These predictions are of great concern given the genetic impoverishment evident in northern parts of the range of P. austriacus, and the genetic evidence from an ancient DNA study questioning the ability of species to track decreases in availability of suitable habitats under climate change (Dalén et al. et al. et al. In line with previous broad-scale predictions for other temperate European bat species (Rebelo P. austriacus indeed represents its climatic tolerance. P. austriacus is absent from North Africa and the Middle East (Spitzenberger et al. et al. Plecotus species across Europe. Moreover, differences between the fundamental and realised niche may be generally small in bats because flight allows bats to disperse widely and colonise the entire potential geographical niche space (Rebelo & Jones It has been debated whether ENM predictions relate to the realised rather than fundamental niche of species, and as such reflect the effects of barriers to colonisation and interspecific interactions rather than the environmental tolerance of species (Elith & Leathwick P. austriacus, from Italy and the Balkans into Western Europe and from Western Europe into England, may already reflect ongoing northward shifts in distribution in response to climate change. However, despite the relatively high rates of estimated gene flow into the English population, we found evidence of a recent decline in population size. This trend of decline suggests that although favourable climatic conditions increased in the past few decades at the northern edge, other factors like habitat loss and modification may limit future range expansions, as has already been shown to be the case for northern-edge butterfly populations in the United Kingdom (Warren et al. The predominantly north-western direction of current gene flow in et al. Availability of suitable climatic conditions at the northern edge does not imply that the ecological conditions necessary for the colonisation and formation of viable populations will be present (Pearson & Dawson P. austriacus even if climate change will result in warmer conditions because of their physical structure and the role of altitude in limiting the distribution of this species. P. austriacus is commonly found at low elevations (Spitzenberger et al. Limited contemporary gene flow across the Pyrenees indicates that this mountain barrier may impede migration out of Iberia. The Pyrenees are likely to remain a barrier for the dispersal of P. austriacus may have limited ability to evolve fast enough to respond to rapid climatic changes (Hoffmann & Sgrò et al. Due to the Pyrenees barrier, much of Iberian genetic diversity may become ‘locked’ inside the peninsula, and population persistence will depend on the phenotypic plasticity or genetic adaptability of Iberian populations. However, evidence of niche conservatism, combined with a slow reproductive rate and a long lifespan, suggest that This study provides a new slant on the importance of conserving edge-of-range populations. We show that former refugial populations that contain the highest genetic diversity due to past climate change are highly endangered due to future climate change. These predictions are relevant to much of European biodiversity that displays similar phylogeographical patterns, and therefore may experience a similar fate. Conservation efforts should also recognise the importance of leading-edge populations, regardless of their current size, due to their role in range shifts and the future spread of genetic diversity. Evolution in marginal atypical environments may allow edge populations to better respond to environmental changes and expand into new habitats, and therefore lead range shifts in response to climate change (Hunter & Hutchinson


Anthropogenic activity is driving population declines and extinctions of large-bodied, fruit-eating animals worldwide. Loss of these frugivores is expected to trigger negative cascading effects on plant populations if remnant species fail to replace the seed dispersal services provided by the extinct frugivores. A collapse of seed dispersal may not only affect plant demography , but should also supress gene flow via seed dispersal. Yet little empirical data still exist demonstrating the genetic consequences of defaunation for animal-dispersed plant species. Here, we first document a significant reduction of seed dispersal distances along a gradient of human-driven defaunation, with increasing loss of large- and medium-bodied frugivores. We then show that local plant neighbourhoods have higher genetic similarity, and smaller effective population sizes when large seed dispersers become extinct  or are even partially downgraded . Our results demonstrate that preservation of large frugivores is crucial to maintain functional seed dispersal services and their associated genetic imprints, a central conservation target. Early signals of reduced dispersal distances that accompany the Anthropogenic defaunation forecast multiple, cascading effects on plant populations. A myriad of vertebrate species have experienced population declines and eventual extinctions matching human expansion, i.e. the “Anthropocene defaunation”135678Large frugivores provide essential seed dispersal services to the plants they feed upon by the large proportions of seeds they disperse over long distances10111315Gallotia, Lacertidae) in the Canary Islands has progressively impaired their seed dispersal services. We further test if this process had a distinct signal on the fine-scale spatial genetic structure of Neochamaelea pulverulenta (Rutaceae), a plant species that relies exclusively on these lizards for dispersalGallotia lizards were abundant in the past but the arrival of first settlers  unleashed a lizard defaunation process resulting in a marked, present-day gradient of seed disperser downsizing across islandsG. stehlini, a setting close to the original situation; Tenerife hosts abundant populations of the medium-sized G. galloti; whereas La Gomera only has an abundant, small-sized lizard, G. caesaris functioning of increasingly defaunated ecosystems, ratcheting downwards in ecological and genetic diversity through the extinction of ecological interactions20th percentile) decreased significantly with the reduction of lizard body size  significantly increased with lizard downsizing. These among islands differences are not attributable to differences in the spatial distribution of either individual plants or seed sampling points among plots  and effective-dispersal distances . Descriptors of seed dispersal distances  and frequency of long distance dispersal events  and the lizards size  when compared to continental South Africa. In our study, the signal of seed dispersal collapse persisted to the established sub-adults, pointing to a long-lasting consequence of frugivore downsizing at the early demographic stages.Lost dispersal services in downsized populations may result in permanent shifts in dispersal patterns, with a legacy of persisting dispersal collapse. Previous studiesEstimates of plant genetic diversity in terms of expected and observed heterozygosity, effective number of alleles, and allelic richness were similarly high across studied plots regardless of the marked differences in the seed dispersal patterns (rij) with distance among pairs of adult plants, we detected significant values spanning longer distances in Tenerife and La Gomera (up to 25 m) than in Gran Canaria (up to 15 m) (K = 1) to Tenerife (K = 2), and La Gomera (K = 3) mirroring the lizard downsizing gradient  . We obtato 15 m) . These tto 15 m) . We foungradient .Gallotia lizard species (see Methods). In addition, these plant populations present similar abiotic  and biotic characteristics Gallotia lizards are the only seed dispersers of N. pulverulenta; thus, the observed reduction of seed dispersal distances following the downsizing is expected to leave a footprint in the spatial distribution of the genetic variation in the long term29Our results suggest a functional link between defaunation-driven downsizing, reduced seed- and effective-dispersal distances, and increased intra-population spatial genetic structure (SGS). These effects showed up at the scale of the 1 ha plots where the potential confounding effects of other factors  would have a marginal influence. The study plots were embedded within large preserved populations that far exceed the home range sizes of N. pulverulenta populations. These findings warn of important alterations in the spatial distribution of plant genetic variation in systems apparently intact after frugivore defaunation, but with partially downgraded dispersal services.Our results support predictions of increased genetic structure when seed-mediated gene flow is reduced132832In sum, the downgrading of seed dispersal services, following body-size reduction of mutualistic frugivores, cascades to the spatial genetic structure with potential negative consequences for plant populations in the long term. These effects include the collapse of the seed dispersal distances, which in turn enhanced fine-scale spatial genetic structure and reduced effective population sizes. We expect similar effects in more diversified frugivore assemblages where limited functional redundancy among species constrains possibilities for ecological replacement11Neochamaelea pulverulenta (Rutaceae) (Vent) Erdtman is a fleshy-fruited shrub (up to 2.7 m height), endemic to the Canary Islands . It is found in lowland xerophytic areas  consume these fruits and act as legitimate seed dispersers172235ic areas , and is ic areas . Each coGallotia lizard species were relatively abundant in the Canary Islands before the arrival of first settlers (c. 2490 ± 60 BP according to C14 dating)18371839N. pulverulenta populationsG. stehlini sub-fossils  to the extant individuals (max SVL = 280 mm). Intermediate downsizing has occurred in Tenerife, from the extinct giant G. goliath species (max SVL = 502 mm) to the medium-sized G. galloti (max SVL = 144 mm). In turn, a substantial body size reduction has been recorded in La Gomera, where the extinct G. goliath (max SVL = 466 mm) was four times larger than the extant G. caesaris (max SVL = 111 mm)  and Gallotia bravoana (max SVL = 212 mm) inhabit Tenerife and La Gomera, respectively, but they survive in extremely reduced, relict populations on very inaccessible cliffs41N. pulverulenta populations in each island (see below).Giant  111 mm) . Also, tN. pulverulenta plants and Gallotia lizards are relatively abundant in all the study sites. In order to increase the likelihood to infer the mother plant of dispersed seeds, the main plot size (1 ha) was established according to previous information on lizard movement patternsN. pulverulenta individual plants within the study plots. Individuals plants were classified as adult (both reproductive and non-reproductive adults), and sub-adult individuals (juveniles and saplings) according to previous information22We chose 10 plant populations encompassing the full geographic range of the plant to represent typical, well-preserved xerophytic scrublands comparable in biotic and abiotic conditionsN. pulverulenta was performed by a regular sampling of lizard-mediated dispersed along 10-m wide transects on Gran Canaria (13 60-m transects), Tenerife (9 125-m transects), and La Gomera (10 80-m transects). Transects spanning the whole of the studied area. Along these transects we regularly established and geo-referenced sampling points every 5 m along the progression line. Around these points we established a circular sampling area of 1 m2 where we collected and silica-dried stored all fresh lizard droppings containing seeds of N. pulverulenta. In addition, these 10 m wide transects were carefully scanned by 2–3 people to increase the number of sampled seeds  in La Gomera plot. The small-sized lizards in this population (G. caesaris) can not swallow N. pulverulenta fruits, but may sporadically disperse some seeds when they handle fruits while biting off the fleshy pulp22The characterization of seed dispersal patterns of N. pulverulenta populations, 3 in Gran Canaria , 2 in Tenerife , and 2 in La Gomera   were used for the polymerase chain reaction (PCR). Plants and endocarps were genotyped for 12 and 10 specific microsatellite markers, respectively, specially designed for parentage assignment of dispersed seeds, and analysis of spatial genetic structurei.e. the average probability that two unrelated individuals share the same multilocus genotype) based on the set of polymorphic microsatellite markers ranged between 6 × 10−10 in Punta Llana and 6 × 10−8 in Teno.DNA was isolated from dried leaves of plants and from endocarps of dispersed seeds ALLELEMATCH packageAs endocarps are tissues of maternal origin, the source plant for all dispersed seeds was assigned by a full matching of the multilocus genotypes of endocarps and any of the candidate mother plants. Because obtaining high-quality DNA from thick-coated endocarps recovered from faeces after some period in the ground, we needed a criterion allowing the inference of a matched genotype given a maximum number of mismatches among paired leaf-endocarp. To do that, we used the algorithm implemented in the i) median, ii) maximum, but also iii) frequency of short distance dispersal , iv) frequency of long distance dispersal , v) frequency of immigrant events, and vi) frequency of immigrant events when accounting for plants growing in the12 m buffer. Finally, we adjusted a non-parametric function (smooth spline curve) and its bootstrap-estimated CI interval to the empirical frequency distribution of seed dispersal distances for each study plot to graphically represent the probability distribution of dispersal events . Secondly, we estimated the frequency distribution of dispersal distance events and the frequency of immigrant events. We tested for differences in the population-level, aggregated, frequency distributions of seed dispersal distances and immigration events resulting from multiple inferences of dispersal events sampled from dispersed seeds. To do that we resampled 999 times the empirical seed dispersal vectors (including immigrant seeds) to obtain bootstrapped estimates of dispersal distances and their associated SD. Then we applied linear models with island as fixed factor and a post-hoc Tukey test to evaluate among-island dispersal distance differences in terms of The frequency distribution of effective dispersal distances were also estimated by applying parentage analyses to sub-adults individuals (saplings and juveniles separately) in 1-ha study plots. We used a maximum-likelihood framework as implemented in CERVUS 3.0 softwareuHe), observed heterozygosity (Ho), effective number of alleles (Ae) and average allelic richness (AR) for each age class  by applying GeneAlex 6.550rij) among pairs of individuals for a set of specified distance classes. Associated standard errors of rij were estimated using bootstrapping procedures. The selection of distance classes was calibrated to result in similar sample sizes. We used the same distance classes (5 m) in the three locations to allow comparisons among them. To test departures from the null-hypothesis  we permuted the spatial position of individuals (n permutations = 999) and then calculated the mean of the 999 permuted values and generated a 95% confidence envelope around that null-hypothesis mean. Plant density is expected to enhance the spatial genetic structure (SGS) of plant populations, however our results showed that the studied plot in Tenerife (with medium-size lizards) showing the highest plant density exhibited lower SGS than La Gomera plot . Thus, variation in plant density seems not to obscure the signal imprinted by body-size reduction of lizards and the associated downgrading of dispersal functions. Finally, the effective population size (Ne/N) was calculated from genotype information of reproductive individuals by using the NeEstimator softwareWe determined among-plot differences on the amount of plant genetic diversity in terms of expected heterozygosity (GENELAND R packageK clusters in Hardy-Weinberg-Linkage-Equilibrium (HWLE). We applied a two-step procedureKmin = 1; Kmax = 50 for 100000 sweeps; thinning = 100; burning = 100. Spatially-explicit models take into account the spatial location of the individuals to improve the inference power of the substructure when differentiation occurs by limited gene flow driven by the presence of physical barriers. The number of genetic clusters (K) was inferred as the modal number of genetic groups of the best run . Secondly, we fixed the number of genetic clusters inferred in the previous step for each study plot and performed 25 independent runs to assign each individual to a cluster. The assignment of each individual to a cluster was set according to the posterior probability of the cluster membership of the best run (threshold = 0.8). Then, we mapped the each individual sorted by clusters by using R 3.1.1We also explored fine-scale genetic structure within plots by searching for genetic clusters of adult plant. We first applied a Bayesian-clustering algorithm, as implemented in How to cite this article: Pérez-Méndez, N. et al. The signatures of Anthropocene defaunation: cascading effects of the seed dispersal collapse. Sci. Rep. 6, 24820; doi: 10.1038/srep24820 (2016).


What kind mechanisms one deems central for the evolutionary process deeply influences one's understanding of the nature of organisms, including cognition. Reversely, adopting a certain approach to the nature of life and cognition and the relationship between them or between the organism and its environment should affect one's view of evolutionary theory. This paper explores this reciprocal relationship in more detail. In particular it argues that the view of living and cognitive systems, especially humans, as deeply integrated beings embedded in and transformed by their genetic, epigenetic (molecular and cellular), behavioral, ecological, socio-cultural and cognitive-symbolic legacies calls for an extended evolutionary synthesis that goes beyond either a theory of genes juxtaposed against a theory of cultural evolution and or even more sophisticated theories of gene-culture coevolution and niche construction. Environments, particularly in the form of developmental environments, do not just select for variation, they also create new variation by influencing development through the reliable transmission of non-genetic but heritable information. This paper stresses particularly views of embodied, embedded, enacted and extended cognition, and their relationship to those aspects of extended inheritance that lie between genetic and cultural inheritance, the still gray area of epigenetic and behavioral inheritance systems that play a role in parental effect. These are the processes that can be regarded as transgenerational developmental plasticity and that I think can most fruitfully contribute to, and be investigated by, developmental psychology. This approach, which subscribes to the computational theory of mind, has been polemically dubbed the “Rational Bubble stance (which) confounds cultural symbolic achievements with individual cognitive competences” and belongs to a class of views that have in recent years come under increasing criticism as a quite unrealistic model of cognitive growth  selection as the driving force, genetic mutations as the creative force and genetic transmission as the only mechanism of heredity. When applied to cognition, the Modern Synthesis invites the decomposition of the mind into separately evolved cognitive traits, called mental modules, each selected to solve a particular evolutionary problem in the human ancestor's “environment of evolutionary adaptedness”  psychology. It will probe which updates to the conceptual structure of evolutionary theory would be needed for its most fruitful application to problems in psychology. The next two sections will explore in more detail two issues that are of particular importance for psychology. Section Beyond Innate and Learned: the Concept of Experience criticizes the conceptual poverty created by the simplistic dichotomy between innate or genetically determined development and acquired learning. It introduces another concept, experience, as a step to bridge between and integrate development and learning. Section Extended Inheritance discusses in more detail the diverse mechanisms of non-genetic inheritance that comprise the central extension to the Modern Synthesis.The alternative conceptions of mind and cognitions to the traditional cognitivist and computationist approach, namely 4E cognition, will stand at the center of Section Embodied, Embedded, Enacted and Extended Organisms, Extended Synthesis and Extended Evolutionary Psychology. In this final section I look in more detail at how this alternative view of the mind is related to the extended view of evolution that I have promoted here, particularly those parts of the new synthesis that I deem to have special explanatory potential for many areas of psychology. A radically different perspective to the view that sees a disembodied mind being passively molded by natural selection and genetic mutations is presented. It conceives living beings as non-linearly coupled organism-environment systems, that come with cellular, social, ecological and cultural legacies bequeathed to them from earlier generations, and who's actions substantially influence the evolutionary process.This section doesn't attempt to review, discuss and criticize in detail the main kinds of evolutionary psychology. There is an extraordinary amount of literature out there doing just that. This presents just a minimalist overview, and as such necessarily presents a bit of a caricature, the three waves of attempts to integrate psychology with evolutionary theory in the last four decades. In the seventies Edward O. Wilson attempted a “New Synthesis” under the name of Sociobiology, which viewed social behavior as the product of evolution and therefore reasoned that it should be explained in terms of adaptive success. Its arguably quite radical gene centrism, promoted particularly through Richard Dawkins' notion of the selfish gene, became the subject of intense criticism. Not entirely without intellectual connections, the nineties saw the emergence of the Santa Barbara school of Evolutionary Psychology. It applies knowledge and principles from mainstream evolutionary theory to psychology and “good old-fashioned” Artificial Intelligence/cognitive science in order to understand the design of the human mind: “In this view, the mind is a set of information-processing machines that were designed by natural selection to solve adaptive problems faced by our hunter-gatherer ancestors”  processes that adapt these competencies to local conditions”  psychology you get. Therefore what follows will be a very short analysis of which kind of amendments or extensions should be included to widen the scope of problems that can be successfully addressed by evolutionary theory. Again, I have to refer to the cited literature for a much more thorough and detailed criticism and further amendment than I could present here; the present paper focuses on those new developments that in my view are most relevant for an extended evolutionary psychology.This section asks what are the implications of recent scientific developments for the mechanisms of evolution. These developments include discoveries in molecular genetics, notably “molecular epigenesist” or “distributed specificity” of gene products, new discoveries of exogenetic heredity, and the revival of notions of epigenesis and developmental plasticity and their implications for evolution. Together with many others I have argued that these developments necessitate an extension of the conventional, neo-Darwinian theory of evolution, the so-called “Modern Synthesis.” Some may argue that the referral to the Modern Synthesis presents something like a straw man argument because many practitioners have, in the intervening decades, assimilated new conceptual and methodological developments into their thinking, often perhaps without being aware to what extent some of these violate the underlying assumptions on which the original synthesis was based. Several of these assumptions are now more than three quarters of a century old, and many of the relevant theories and concepts have undergone major revisions. So the point of the call for an “extended synthesis” may be as much to think through the implications of changes that have occurred or are occurring as to call for more change  that determine the linear structure of a gene product  code for the amino acid sequence of a particular protein.The Central Dogma This states that once “information” has passed into a protein it cannot get out again. In more detail, the transfer of information from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino-acid residues in the protein. , and thirdly by creating new sequence information through the insertion, deletion or exchange of single nucleotide letters of the RNA message (RNA editing). Thus specificity, and hence Crick information, is distributed between a myriad of factors other than the original coding sequence: Non-coding DNA sequences with regulatory functions, diverse gene products such as transcription, splicing and editing factors , and non-coding RNAs  differ in several important ways from genetic inheritance: epigenetic variations may be less stable, because these variations are in principle reversible, and many organisms have developed safeguards against their transgenerational transmission. These features are not necessarily a disadvantage: in comparison to genetic inheritance, epigenetic mechanisms are more sensitive to the environment, which might make them more directed, more predictable, and also more flexible. These are all features which potentially render them more adaptive in the short term than blind genetic variation, particularly in variable environmental conditions . In genetic inheritance systems, on the other hand, correlational information requires a process of selection that builds up gene frequency differences between environments. Uller, .There are now a variety of scientific fields interested in the extent to which development influences evolution, and the ideas about which mechanisms are evolutionarily relevant differ greatly: The most radical position asserts that environmentally induced and developmentally regulated variation in exogenetic, developmental resources may be transmitted directly to the next generation either from germ or soma cell to germ cell, or from soma to soma, in order to create heritable variation in the phenotype  may uncover the existence, or facilitate the production, of suitable genetic change. Such genetic variation may lead via natural selection to either genetic assimilation , or genetic accommodation, in other words the genetic inheritance of either decreased or increased responsiveness to environmental conditions  enable the persistence and even the spread of the induced phenotype by modifying selection pressure .So, while many still argue to what extent the transference of non-genetic resources influences population dynamics and the rate and direction of phenotypic evolution, here I want to advocate to want to advocate the extent to which it can provide more adequate answers to a wide range of central evolutionary questions .Maintenance of traits: stabilization of the developmental and selective niche.Reliable (re)production of traits: entrenched extended inheritance mechanisms  . My understanding of experience follows its original definition by the American animal psychologist Theodore Christian Schneirla, quoted by his student Daniel Lehrman: “Experience is ‘the contribution to development of the effects of stimulation from all available sources , including their functional trace effects surviving from earlier development’ . They challenge overly gene-centered and pre-deterministic as well as environmentalist explanations of behavior. Nature and nurture don't interact as if they were separated entities, with nature as the m Oyama, .Do we find learning or cognition in bacteria? The answer depends very much on your definition of learning and experience. Possibly yes, if “environment” is understood as the source of a “quite heterogeneous mix of resources called experience” Moore, , p. 350 The study of behavior and cognition looks at three interconnected time-scales: evolution, development, and situated behavior. The integration of the first two seems possible now, and there are successful attempts at integrating the second two in areas of psychology, namely developmental psychobiology and social neuroscience  parental effects, and their interaction. More formally, we can say that a parental effect is a correlation between offspring and parent phenotypes that is statistically independent of the correlation between their genotypes.Parental effects are received as part of the environmental component of offspring phenotypes. The environment provided by the mother for her offspring is a very important factor in causing fitness differences among newborns and weanlings, particularly in organisms with extensive parental care. In environmentally induced parental effects the environment experienced by the parental generation influences the phenotype of the offspring. In locusts, an environment overcrowded with conspecifics experienced by the mother causes her to coat her eggs with a hormonal substance containing serotonin, which induces the egg to develop into a high-density morph with wings and legs suitable for migration. Many parental effects, like this one, enhance the offspring's fitness. Natural selection has shaped offspring to respond to subtle variations in parental behaviors or parental provisioning as a forecast of the environmental conditions they will ultimately face after independence from the parent ; cytoplasmic inheritance ; oviposition ; gut organisms ; sex determination ; nutritional provisioning ; parental care and rearing practices ; social status , among other things ; territorial and habitat inheritance  in woodpeckers and jays; maternal rank inheritance in carnivores and primates . A radically different perspective views living beings as non-linearly coupled organism-environment systems, whose actions substantially influence the evolutionary process via two different pathways: the developmental creation of potentially directed or adaptive variations, and the active construction of the population's niche and hence the selection pressures acting on it. Under the latter perspective it shouldn't matter if you start with a revised vision of the nature of life and cognition or a revised vision of the nature of the mechanisms that underlie the process of evolution. One should prescribe the other.The modern synthesis asserts that mutation in genes provide the only  variations and the slow process of natural selection acting on these variations is its direction-giving, order-producing or creative force. Genetic variations determine the organism's characteristics, which in turn influence its fitness, i.e., its ability to survive and reproduce. Genetic inheritance renders these fitness differences hereditary. Since evolution is defined as changes in gene frequencies, it is implied that development, including potential developmental modifications through phenotypic plasticity or the behavior of organisms, plays no role in this process. The causes of phenotypic variation, evolution's main currency, are solely genetic: blind mutation, sexual recombination, genetic drift and gene flow. Additionally, natural selection is the result of hostile external forces on populations, a “struggle for existence” which results in the “survival of the fittest.” Both take place without any acknowledged influence of the organism—with the notable exception of sexual selection, already envisioned by Darwin as a secondary mechanism of selection, which is greatly influenced by the choice of an organism's choice of sexual partners. In the seventies, ideas of evolutionary game theory, the competition between different genetically inherited strategies of survival and reproduction, were added. Today we also have theories of coevolution, such as gene-culture coevolution, and niche construction. These theories all work by recognizing that populations influence, to some extent, their own selection pressures. The main reason for this relative neglect of the organism in the modern synthesis was that any influence by the developing organism that is not originally caused by its genetic make-up was assumed to not leave any trace effects on its descendants. And so it comes as no surprise that the main equations in population genetics, the formal backbone of the modern synthesis, calculate frequency and interaction of alleles and genes in populations, without any mention of the organism.The adapted mind of evolutionary psychology has a cognitive foundation of innate, content-rich mental modules, supposed to be universally shared by all humans. EP proposes that strong selective pressures during the ancestral environment of evolutionary adaptedness (EEA) have accounted for the evolution of these faculties, shaped by environmental problems of the human's ancestor in the Pleistocene. They include not only sets of rules and algorithms for problem-solving and other mental faculties, but consist of concrete information reflecting the structure of the real world at the time when our mental capacities were meant to have evolved.The alternative view of evolution as the “change in the distributions and constitution of developmental systems” does not posit a population of static and passive entities. Instead of random mutations and drift, developmental plasticity produces variable and active organisms that engage with their environment. The core of heredity, one of the main supporting beams of the received view, doesn't have to be the persistence of traits due to un-interrupted channels of genetic transmission. Instead, self-organizational properties of the system actively create and construct both stability (heredity) and variability (adaptability) through the availability of developmental resources in every generation. Table As argued here, an extended evolutionary theory is reciprocally related to the view of a cognitive system as embodied, embedded, enacted, and extended, promoted recently by many proponents in cognitive science. There are plenty of older thinkers who have promoted similar ideas and present therefore part of the heritage of this viewOf course the most fruitful, most obvious field of study would be reconstituting human history—the history of human thinking in prehistoric man. … Since this field of biogenesis is not available to us, we shall do as biologists do and turn to ontogenesis. Piaget, , p. 13.subject and no object. Both result from the internal organization of the subject's experience with the external. For Piaget, boundaries between the cognitive subject and the outside object were not given qualities but created categories of the world. The cognitive system was the subject-environment unity. Piaget attempted to show the constructivist-interactionist power between the two antagonistic mechanisms of life: organization and adaptation - maintenance and change - essential for every natural process, like development, evolution, and cognition. Development, in this view, is the construction of all kinds of causal factors—genetic, epigenetic, ecological, social and cultural factors—which interact together in a self-organized and not centrally controlled manner . Piaget emphasized the emergence of cognitive abilities out of a groundwork of sensorimotor abilities. At the beginning of an interaction there is no r Stotz, . His undBefore going through the main tenets of evolutionary theory, variation, heredity, selection and adaptation, and the role the active organism is playing in all of them, we first have to address the very preconditions for biological evolution. Organisms as they exist today may owe their existence to evolution, but the evolutionary process in turn crucially depends on the existence of living systems that exhibit the necessary preconditions, namely the capacity to (a) produce variation (variability), (b) transmit information for the reconstruction of the life cycle to the next generation (heritability), and (c) adapt the behavior to the contingencies of the environment (adaptability). In summary, populations of organisms must exhibit the ability to evolve, the production of heritable variation in fitness, i.e., differential reproductive success (evolvability). These preconditions, if fulfilled, produce natural selection. Organisms are not just actively engaged in the business of being alive—“acting on their own behalf”  biology, most notably Developmental Systems Theory and the theories of (selective) and developmental niche construction.These two views are sometimes seen as mere analogies to each other. From the view of embodied and enacted cognition, in particular, this should immediately be seen as a mistake. The developmental construction intimately relates to the construction of cognition, since biological brains are the control systems for biological bodies. Cognition is the organism's permanent interaction with the world. Even more so in organisms with complicated brains while interacting with the world they permanently construe this world, which in turn influences its impact on development. The mind can only be understood in the context of its relationship to a physical body, which allows it to interact with the world. This world in turn is part of the biological and cognitive system. The body or the mind alone is often not a meaningful unit of analysis because of the dense and continuous information flow between mind, body and world.The relationship between an active developing system with exploring cognitive abilities and its capacity to construct its own living environment—and that for its descendents—becomes immediately obvious. Since the organism-environment relationship creates selection pressures that will have an important feedback on the phenotype of future generations, the organism indirectly and partially controls its own evolution. This argument has been extensively developed and defended by Odling-Smee, Laland and Feldman e.g., . The impOnly quite recently did new mechanisms come to light that showed to what extent heredity is indeed a developmental achievement, as the embryologists of the nineteenth century have argued. First, epigenetic mechanisms inherited through the germline made the idea more palatable to biologists, for whom any transmission outside the germ line was previously principally excluded from consideration. There were earlier hypotheses, notably genetic assimilation and accommodation, that that afforded explanation seemingly Lamarckian phenomena by genetic inheritance, widely construed. But since inheritance has now been somewhat detached from its dogmatic relationship with the genetic system, it becomes possible to interpret other transgenerational transmissions as inherited. Parental effects have long been recognized as a main contributor to the offspring phenotype. This phenotype develops out of contributions received from the parents  and environmental contributions. Why should some of these trans-generationally transmitted resources not be accepted as contributing to the inheritance of the offspring, as long as they influence the dynamics of evolution?But all of these exogenetic contributions of inheritance rely critically on the active organism embedded in its own niche, namely caring for its offspring , and the organism's complex relationship with its offspring that actively co-construct the offspring's developmental niche. Epigenetic, behavioral, ecological, and epistemic inheritance depends on the environment experienced and provided by the parent.This paper couldn't possibly focus on all aspects of an extended evolutionary synthesis and has chosen the, from the author's perspective, most important but also most highly debated aspect, namely non-genetic inheritance. Within this area the paper has barely touched cultural inheritance because most papers on extended inheritance and its importance particularly for human development and evolution has focused on that. Instead it stressed particularly those aspects of extended inheritance that lie between genetic and cultural inheritance, the still gray area of epigenetic and behavioral inheritance systems that play a role in parental effects. These are the processes that can be regarded as transgenerational developmental plasticity and that I think can most fruitfully contribute to, and be investigated by, an extended evolutionary psychology.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Agroecology, as a scientific approach, relies on a better knowledge of biodiversity at all levels of organization and function, in order to better manage agricultural production systems, from farm scale to landscape. Ecological concepts such as functional redundancy, complementary use of resources, can be applied to farming systems, with the purpose of improving their resilience. Transposing the concepts of agroecology to livestock production has been recently proposed by Dumont et al. . One of How the agroecology concepts can be applied to farm animal genetic resources and how the genomics approach may be used to facilitate it?Biodiversity in livestock production systems may be considered at all scales, from individuals and breeds to species and ecosystems. Several levels may be considered to increase biodiversity in livestock production systems, such as intermixing species within production systems. This paper will focus on within-species biodiversity that goes from local breeds to highly selected populations. At the population scale, one possibility is to increase the number of breeds in use, or to produce new composite populations, as done for the Creole cattle in the French West Indies  cattle chip is the most used and the cheapest SNP array. Other requirements are that breeders have easy access to the genotyping results, through their breeding organization or technical services, and to guidelines explaining how to use these results to monitor the diversity within herds. The benefit is to maximize genome diversity and the overall genetic resource within the herd. Research is needed to prove that maximizing genetic diversity will indeed improve the tolerance of the herd to climate change and extreme events which are likely to become more frequent, and guarantee a stable performance of the group, which is an important objective for the farmer. Genomic selection and individual dairy cow genotyping are producing large datasets suitable to test such a relationship between genetic diversity and herd resilience to extreme events. This would represent a change in breeding methods, since the best herd will not be an ensemble of the best animals but the best set of diverse animals.The second one is the association of genomic regions with a range of phenotypes or performance levels. Monitoring these regions may provide a tool to tailor the genetic make-up of a herd with regards to specific traits that need to be combined at the herd level. This approach targets specific aptitudes to be combined, going beyond the first approach which aimed at verifying that the herd harbors a sufficiently high diversity, leaving options for future choices. The main challenge is to define the relevant phenotype to be predicted with molecular markers. Which phenotypes correspond to environmental or socio-cultural services? Research is needed on these issues, in close connection with the farmers, who are willing to better characterize their breed and raise awareness about its value, and with other actors who are benefiting from the service. Genomic regions associated to a desired trait or service should be validated at a large scale so that their effect is likely to be observed in any herd or any herd x environment combination. However, environmental services may depend on the herd location and be difficult to assess on a large scale because of genotype by environment interactions (GxE). In this case the farmer may choose a specific genetic profile for its herd.The third one is targeting local breeds, where genomic selection and large scale reference populations are not available. There are two main issues for these breeds: managing their genetic variability and characterizing their specific features. Such breeds harbor original characteristics, either for product quality, or adaptation to specific environments, but the genetic basis for these characteristics is seldom known. If farmers had access to this information, how would they use it? What if adaptive features involved epigenetic changes that cannot be tested by standard SNP genotyping? Research is obviously needed in this regard. The use of such information may require a change of scale in the breed management, to record more traits and share more data between herds. This is more an organizational challenge and a social issue than a genetic issue. Furthermore, the identification of original features in local breeds may trigger the onset of crossbreeding programs to introduce such features in commercial populations, which raises strong issue for benefit sharing and for preserving breed specificities. Implementing genomics for the management of genetic variability appears relatively easy, provided that the genotyping cost is affordable, which is not so obvious for small populations. To share costs, a multi-breed genotyping tools could be an option to explore. With this approach, farmers will get accurate information about drift, population fragmentation or introgression events affecting a breed. Population fragmentation is typically expected when small size herds do not exchange animals, to a point that the genetic difference can be very high among them. Such a situation with a low within-herd variability but a high between herds variability could be favorable at the breed level from the viewpoint of agroecology (diversity and complementarity between herds) but it might question the breed definition and the breed identity. The same issue could appear if introgression events are detected: the breed would not anymore be the “pure” local breed as often described, even though this introgression could contribute to the breed evolution and facilitate its adaptation to future conditions. It is not to be excluded that the genomic characterization will enhance social issues, revealing how farmers are managing their breed.In conclusion, setting the management of animal genetic resources in an agroecological perspective raises two major issues where research is needed: the possible transposition of ecosystem services to animal breeding and the impact of genomic tools on the breed concept and the management of genetic diversity at different scales.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Human survival probability and fertility decline strongly with age. These life history traits have been shaped by evolution. However, research has failed to uncover a consistent genetic determination of variation in survival and fertility. As an explanation, such genetic determinants have been selected in adverse environments, in which humans have lived during most of their history, but are almost exclusively studied in populations in modern affluent environments. Here, we present a large-scale candidate gene association study in a rural African population living in an adverse environment. In 4387 individuals, we studied 4052 SNPs in 148 genes that have previously been identified as possible determinants of survival or fertility in animals or humans. We studied their associations with survival comparing newborns, middle-age adults, and old individuals. In women, we assessed their associations with reported and observed numbers of children. We found no statistically significant associations of these SNPs with survival between the three age groups nor with women's reported and observed fertility. Population stratification was unlikely to explain these results. Apart from a lack of power, we hypothesise that genetic heterogeneity of complex phenotypes and gene-environment interactions prevent the identification of genetic variants explaining variation in survival and fertility in humans. APOE [Age patterns of survival and fertility vary widely across species . During APOE –11. GeneAPOE , 13, butAPOE .Research on the genetic determinants of human life history has almost exclusively been conducted in populations living in modern affluent environments. These modern affluent environments, however, are radically different from the environments in which over many generations humans have been subjected to evolutionary pressures. During most of human history, survival and fertility were compromised by infectious diseases , 16, malIf we aim to identify the genetic determinants of life history that have enhanced fitness in adverse environments, we should search for them in such environments. In this study, we investigate genetic variants that determine life history through variation in survival and fertility in a traditional rural African population that lives in such an adverse environment. Compared with modern affluent environments, this population's mortality rates and fertility rates are high, various infectious diseases are endemic, periodic food shortage and malnutrition are common, and a sedentary lifestyle is absent –29.Table As shown in Figure Figure p values for the association with survival between each pair of age groups in IRS2) and rs2069842 in the interleukin 6 gene (IL6), both of which were in the lists comparing newborns and old individuals and comparing newborns and middle-aged adults.Although each was non-significant, we list the ten SNPs with the lowest Figure p values for the associations with observed and reported fertility in Although each was non-significant, we list the ten SNPs with the lowest The aim of this study was to identify the genetic variants that determine life history through variation in survival and fertility in a traditional rural African population that lives in an adverse environment without a western lifestyle. We conducted a large-scale candidate gene study using a high density of SNPs. We found no statistically significant association of any genetic variant with either survival or fertility.Studies on the genetic determinants of variation in human survival and fertility in adverse environments have never been executed with numbers of individuals and SNPs comparable to this study. Due to a lack of previous genetic studies in this region, we could not rely on standard genome-wide association analyses given the higher degree of population stratification and the lesser degree of linkage disequilibrium in African populations . InsteadPopulation stratification was unlikely to explain our results. As a result of the polygynous and patrilocal culture in the research area, men preferentially marry women from outside the region. Previous analyses of this study population have confirmed that the female-mediated gene flow is nearly fully random and prevents population stratification of autosomal genes . To accoAPOE, and most of their associations with survival are not strong [Here we did not find genetic variants that were statistically significantly associated with variation in survival or fertility. This finding corresponds with the difficulty to identify such variants in modern affluent environments. In such environments, variation in human lifespan is genetically determined for only less than 30%. Many and various studies have yielded consistent evidence for only a handful of genetic variants to determine variation in survival, most notably t strong –10. Genet strong . These dt strong .APOE as a determinant of variation in survival. Three SNPs in APOE were included in the present analyses: rs1081101, rs877973, and rs769450. The p values for their associations with survival ranged between 0.36 and 1.00. In West Africans, only the latter of these SNPs is in linkage disequilibrium (r2=0.21) with rs429358, the SNP that constitutes the APOEε4 allele and most consistently determines variation in survival in modern affluent populations, but contrary to rs429358, it does not influence blood lipid levels. The other two SNPs are not in linkage disequilibrium with rs429358 and influence blood triglyceride, but not cholesterol levels [Contrary to many studies in affluent populations, the present study did not identify l levels .APOE, did not influence survival in adverse environments may likely be explained, apart from chance, by gene-environment interaction. The effects of genes vary depending on environmental conditions, which thus determine the effects of genes on survival and fertility [APOE affect blood lipid levels, the risk of cardiovascular disease, and survival in affluent populations [APOE does not affect survival here. The higher levels of physical activity may provide an additional explanation for the absence of such an effect [IL10, associated with the inflammatory strength of the immune response, enhance survival in those exposed to contaminated drinking water, but diminish survival in those exposed to clean drinking water [Our finding that genetic variants known to influence survival in modern affluent populations, such as ertility . Our stuertility –29. Thesulations . In thisulations –28, whicn effect . Likewisng water . These eLife histories have evolved as natural selection has optimised fitness by increasing the frequencies of genetic variants that enhance survival and fertility, while decreasing the frequencies of genetic variants that diminish survival and fertility. The effects of genetic variants on survival and fertility, and thereby the evolution of life history, are largely dependent on environmental factors . The divEvolutionary theory predicts that most of the genetic variants that enhance survival diminish fertility or vice versa, because a trade-off exists between investments in survival and investments in fertility , 38. IndIt is critical to acknowledge that natural selection works to maximize fitness as a phenotype rather than a genotype, with survival and fertility being the most important components of this phenotype. The genotype only matters to natural selection as a determinant of the phenotype that is under selection. Meanwhile, the phenotype may be the result of a complex interaction between various genetic variants. Natural selection exists by virtue of such variation in the genetic determinants. Genetic variation is conserved, since genes are prone to mutations and new genetic variants are introduced by sexual reproduction. The resulting genetic heterogeneity of populations may explain why so few unique genetic variants have been found to determine variation in the complex phenotypes of survival and fertility. If different genetic variants determine a similar phenotype, each of these genetic variants is shared by only a proportion of the individuals and a patchwork of shared and unshared variants is established throughout the population. Moreover, if different genetic variants interact with each other to express a phenotype, the penetrance of one of these genetic variants relative to another may vary throughout the population. When studied in a population as a whole, these patterns lead to annulation of the effect of a single genetic variant. As an example of genetic heterogeneity underlying a single phenotype, the ability to digest milk after childhood due to lactase persistence has independently evolved multiple times in similar environments of animal domestication. Across populations, various SNPs at different positions in the lactase gene bring about this trait. Still, these specific variants are insufficient to explain differences in the frequencies of lactase persistence across populations , 42. MetIn conclusion, we aimed to identify the genetic variants that determine life history through variation in survival and fertility in an adverse environment in rural Africa, which resembles the environments during most of recent human evolution. In this large-scale candidate gene study, we did not find statistically significant associations of genetic variants with survival or fertility. Apart from a lack of power, we hypothesise that genetic heterogeneity of complex phenotypes and gene-environment interaction prevent the identification of such unique genetic variants that humans have been selected for.This study was conducted in the Garu-Tempane District in the Upper East Region in Ghana. The region is rural, remote, and one of the least developed in the country. The vast majority of the inhabitants are involved in subsistence agriculture performed by manual labour without proper means of transportation or mechanized farming. The mean annual per capita income and expenditure in the region are one third of those in Ghana nationally and one fifth of those in the capital Accra . Of the 2 comprising 32 villages. During annual visits we registered the name, age, sex, tribe, and location of living of each inhabitant. If an inhabitant's age was unknown, it was estimated by oral methods, as described previously [Plasmodium falciparum, 44% by the protozoan Giardia lamblia, and 31% by the helminth Necator americanus [From 2002 through 2011, we kept a demographic registry of the population in a research area of 375 kmeviously . Househoeviously . Annual eviously , 45. Drieviously . Of appaericanus . During ericanus .Ethical approval was given by the Committee Medical Ethics of the Leiden University Medical Center, the Ethical Review Committee of Ghana Health Services, and the local chiefs and elders. Because of illiteracy, informed consent was obtained orally from the participants after explanation of the purpose and conduction of this research project. The data were analysed anonymously. This study was conducted in accordance with the Declaration of Helsinki.Survival of all inhabitants was registered during the annual follow-up from 2002 through 2011 . FertiliTo identify genetic variants associated with survival, we aimed to contrast the genotypes of newborns, of middle-aged individuals, and of individuals who had survived to old age. To identify genetic variants associated with fertility, we aimed to associate the genotypes of middle-aged and postmenopausal women with their reported or observed fertility. Since 2003, we took buccal samples from all newborns who were present during our visits, older than one week, and born in the same year. We took buccal samples from men and women of the fertile ages from 20 through 44 years, from women aged 45 years and older, and from men and women aged 60 years and older. The buccal samples of middle-aged and older individuals were collected together with measurements of phenotypic characteristics, including fertility , 47, infThe buccal samples were stored in 2.5 ml STE buffer  with 0.05 mg/ml proteinase K, 0.1 mg/ml pronase, and 0.5% sodium dodecylsulphate. DNA was isolated and processed from samples collected in 2002 through 2006 by BaseClear  using a Chemagic bead-extraction method, from samples collected in 2006 through 2008 by the Department of Molecular Epidemiology of Leiden University Medical Center  using Qiagen silica spin-columns, and from samples collected in 2007 through 2011 by LGC Genomics, formerly KBioscience , using a proprietary silica column method. DNA was genotyped using a custom-made Illumina Infinium iSelect High-Density Custom Genotyping BeadChip  at the Department of Human Genetics of Leiden University Medical Center following the manufacturer's instructions.For the genotyping and analyses, we selected 153 candidate genes that were considered relevant for regulation of life history based on literature, discussion with experts, and general inference. These candidate genes included genes associated with survival or fertility in genome-wide association studies in humans or model organisms , human gWe aimed for a dense coverage of SNPs in the candidate genes. We selected SNPs that are known to be causally associated with survival or fertility in humans, had a minor allele frequency equal to or higher than 1% and a correlation equal to or higher than 0.8 in the Yoruba population , and/or After genotyping, buccal samples and SNPs were subjected to a stringent quality control protocol. Of the 6104 individuals from whom buccal samples had been taken, we excluded 370 (6.1%) because of genotyping failure. Furthermore, we excluded 98 (1.6%) individuals with a call rate below 90%, 542 (8.9%) individuals with a sex mismatch, 3 (< 0.1%) individuals with an excess of heterozygosity indicated by an inbreeding coefficient below −0.3 or above 0.3, and 492 (8.1%) individuals with a different allele at less than 10% of the loci indicated by an IBS1 below 10%, which included unintentional duplicates. Of the 4599 individuals eligible for analysis, 212 (4.6%) individuals outside the designated sex and age groups were excluded. Of the 9509 genotyped SNPs, we excluded 1162 (12.2%) because of genotyping failure. Furthermore, we excluded 581 (6.1%) SNPs with a call rate below 90%, 3646 (38.3%) SNPs with a minor allele frequency below 1%, and 68 (0.7%) SNPs that were not in Hardy-Weinberg equilibrium. As a result, 4387 individuals and 4052 SNPs were included in the analyses. Of these SNPs, 98 (2.4%) were evolutionarily neutrally selected controls. The exclusions and inclusions are described in Figure As previously reported for this study population, population stratification is unlikely to influence any associations with genetic variation in autosomal genes. As a result of the polygynous and patrilocal culture in the research area, the female-mediated gene flow is nearly fully random . Multidi−5 for the logistic and linear regression models and at 1.61 × 10−5 for the Andersen-Gill model. The analyses were performed using R .For the investigation of the genetic determinants of survival, we assessed the association of each SNP with the chance of being in one of three age groups: newborns, middle-aged adults of fertile ages from 20 through 44 years, and old individuals aged 60 years or over. We compared the chances between pairs of these groups using an additive logistic regression model adjusted for sex. For the investigation of the genetic determinants of fertility, we assessed the associations of each SNP with observed fertility in middle-aged women of fertile ages from 20 through 44 years and with reported fertility in postmenopausal women aged 45 years and older. We assessed the association with reported fertility using an additive linear regression model. We assessed the association with observed fertility using an Andersen-Gill model, which is an extension to the Cox regression model for analysis of recurrent events . The mod