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Bernard J Crespi,1 Susan F Evans2 1Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada; 2Adelaide Medical School, School of Medicine, University of Adelaide, Adelaide, South Australia, AustraliaCorrespondence: Bernard J Crespi, Email crespi@sfu.caAbstract: Endometriosis is a polygenic, estrogen-dependent, inflammatory disorder of uncertain aetiology associated with pain, infertility and reduced quality of life. While the positive association between endometriosis and estrogen is established, a suite of recent studies has demonstrated an inverse association between the presence of endometriosis lesions and levels of testosterone both prenatally and postnatally. The following narrative review provides new insights into the roles of testosterone in the aetiology, diagnosis, and management of endometriosis and associated symptoms, especially pain. A relatively short anogenital distance (AGD) is indicative of lower levels of testosterone during fetal development. A shorter AGD has recently been correlated with both a higher risk of developing endometriosis in adult life, and with known correlates of endometriosis including earlier onset of reproductive cycling, lower ovarian follicle number, lower postnatal testosterone, and premature ovarian insufficiency. During adult life, lower levels of testosterone are positively associated with key comorbidities of endometriosis, including days per month of pelvic pain and increased pain sensitivity. Biochemically, lower levels of testosterone are associated with higher levels of pro-inflammatory IL-1β and lower levels of β-endorphin. In rodents, prenatal administration of testosterone to females reduces their pain sensitivity in adulthood. The emerging convergent links of endometriosis with low prenatal and postnatal testosterone provide evidence of a centrally mediated effect beginning in early prenatal development, and persisting through adult life, with notable effects on pain sensitivity. They generate a novel conceptual framework for understanding, studying and treating this disorder, whereby endometriosis is mediated by a combination of high estrogen in endometrial tissue with low systemic and ovarian testosterone.Keywords: endometriosis, pain, testosterone, anogenital distance, fetal development

Nausea and vomiting in pregnancy (NVP) is heritable, common and aversive, and its extreme, hyperemesis gravidarum (HG), can be highly deleterious to the mother and fetus. Recent influential studies have demonstrated that HG is caused predominantly by high levels of Growth-Differentiation Factor 15 (GDF15), a hormone produced by the placenta in substantial amounts. This work has led to calls for therapeutic modulation of this hormone to reduce GDF15 levels and ameliorate HG risk. I describe three main lines of evidence relevant to the hypothesis that GDF15 production is typically adaptive for the fetus, in the context of enhanced placental invasion, reduced rates of miscarriage and preterm birth and higher birth weight. These considerations highlight the medical implications of maternal-fetal conflict, in the context of tradeoffs between aversive symptoms during gestation, rare disorders of pregnancy with major adverse effects and moderate fitness-enhancing benefits to fetuses., Competing Interests: The author has no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)

Genetic variation in CD38-a putative oxytocin pathway gene-has been linked to higher oxytocin levels, empathy, and sensitive parenting, but also to more negative interpersonal outcomes (e.g., alienation from friends and family, poorer romantic relationship quality). To reconcile these seemingly contradictory findings, we drew upon the idea that CD38 variation may heighten social-emotional sensitivity and, consequently, make individuals prone to negative emotions in distressing interpersonal situations. To test this hypothesis, we performed a secondary analysis of a dataset including participants' (n = 171; 94 females) empathic concern ("sympathetic") and distress-related ("anxious") responses to an emotional video. Distress responses were higher for the CD38 rs3796863 AA/AC group vs. the CC group (p = 0.03, η 2  = 0.027); however, there was no significant effect of genotype for empathic concern responses to the video or for indices of trait empathy. These findings provide preliminary evidence that, in the face of an interpersonal stressor, CD38 genetic variation may predict more self-focused, aversive emotional reactions. More broadly, this finding highlights the need to adopt a more nuanced perspective in which the influence of oxytocin system variation (assessed by oxytocin-related genetic variation) should be considered in light of the social context., (© 2024. The Author(s).)

I suggest that the current study of autism is problematic, due to: (1) its failure to pursue a medical model of disease causation, with protocols for differential diagnoses of causes; (2) a notable incidence of unrecognized false positive diagnoses in children; (3) the conceptual equating of autism with sets of traits that have been shown to be genetically and phenotypically unrelated to one another; and (4) the expansion of use of the terms "autism" and "autism traits" to psychiatric conditions that have no substantive etiological or symptomatic overlap with autism. These problems can be alleviated by, like Kanner, considering autism as a syndrome, a constellation of traits, conceptualized as differences rather than deficits, some set of which is found in each affected individual to some degree. The original, prototypical form of autism can be delineated based on the "hallmarks" of autism: a set of core traits, originally explicated by Kanner, that defines a relatively-homogeneous group, and that connects with the larger set of autism symptoms. The hallmarks of autism provide a touchstone for research that is unambiguous, historically continuous to the present, and linked with major theories for explaining the causes and symptoms of autism. Use of the hallmarks of autism does not impact recognition and treatment of individuals with DSM diagnosed autism, or individuals with the many disorders that involve social deficits. This perspective is compatible with the research domain criteria approach to studying autism, via analyses of autism's constituent traits and the differential diagnosis of its individual-specific causes., Competing Interests: 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., (Copyright © 2022 Crespi.)

Video games are popular and ubiquitous aspects of human culture, but their relationships to psychological and neurophysiological traits have yet to be analyzed in social-evolutionary frameworks. We examined the relationships of video game usage, motivations, and preferences with autistic and schizotypal traits and two aspects of neurophysiology, reaction time and targeting time. Participants completed the Autism Quotient, Schizotypal Personality Questionnaire, a Video Game Usage Questionnaire, and two neurophysiological tasks. We tested in particular the hypotheses, motivated by theory and previous work, that: (1) participants with higher autism scores would play video games more, and participants with higher schizotypy scores would play video games less; and (2) autism and positive schizotypy would be associated with opposite patterns of video game use, preferences and motivations. Females, but not males, with higher autism scores played more video games, and exhibited evidence of relatively male-typical video game genre preferences and motivations. By contrast, positive schizotypy was associated with reduced video game use in both genders, for several measures of game use frequency. In line with previous findings, males played video game more than females did overall, preferred action video games, and exhibited faster reaction and targeting times. Females preferred Puzzle and Social Simulation games. Faster reaction and targeting times were associated with gaming motives related to skill development and building behavior. These findings show that gaming use and patterns reflect aspects of psychology, and gender, related to social cognition and imagination, as well as aspects of neurophysiology. More generally, the results suggest that video game use is notably affected by levels of autistic and schizotypal traits, and that video games may provide an evolutionarily novel medium for imaginative play in which immersive play experiences can be decoupled from social interaction., Competing Interests: 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., (Copyright © 2022 Yang, Hurd and Crespi.)

Evolutionary and comparative approaches can yield novel insights into human adaptation and disease. Endometriosis and polycystic ovary syndrome (PCOS) each affect up to 10% of women and significantly reduce the health, fertility, and quality of life of those affected. PCOS and endometriosis have yet to be considered as related to one another, although both conditions involve alterations to prenatal testosterone levels and atypical functioning of the hypothalamic-pituitary-gonadal (HPG) axis. Here, we propose and evaluate the novel hypothesis that endometriosis and PCOS represent extreme and diametric (opposite) outcomes of variation in HPG axis development and activity, with endometriosis mediated in notable part by low prenatal and postnatal testosterone, while PCOS is mediated by high prenatal testosterone. This diametric disorder hypothesis predicts that, for characteristics shaped by the HPG axis, including hormonal profiles, reproductive physiology, life-history traits, and body morphology, women with PCOS and women with endometriosis will manifest opposite phenotypes. To evaluate these predictions, we review and synthesize existing evidence from developmental biology, endocrinology, physiology, life history, and epidemiology. The hypothesis of diametric phenotypes between endometriosis and PCOS is strongly supported across these diverse fields of research. Furthermore, the contrasts between endometriosis and PCOS in humans parallel differences among nonhuman animals in effects of low versus high prenatal testosterone on female reproductive traits. These findings suggest that PCOS and endometriosis represent maladaptive extremes of both female life-history variation and expression of sexually dimorphic female reproductive traits. The diametric disorder hypothesis for endometriosis and PCOS provides novel, unifying, proximate, and evolutionary explanations for endometriosis risk, synthesizes diverse lines of research concerning the two most common female reproductive disorders, and generates future avenues of research for improving the quality of life and health of women., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Imprinted genes mediate fetal and childhood growth and development, and early growth patterns drive fetal programming effects. However, predictions and evidence from the kinship theory of imprinting have yet to be directly integrated with data on fetal programming and risks of metabolic disease. I first define paternal-gene and maternal-gene optima with regard to early human growth and development. Next, I review salient evidence with regard to imprinted gene effects on birth weight, body composition, trajectories of feeding and growth, and timing of developmental stages, to evaluate why and how imprinted gene expression influences risks of metabolic disease in later life. I find that metabolic disease risks derive primarily from maternal gene biases that lead to reduced placental efficacy, low birth weight, low relative muscle mass, high relative white fat, increased abdominal adiposity, reduced pancreatic β-cell mass that promotes insulin resistance, reduced appetite and infant sucking efficacy, catch-up fat deposition from family foods after weaning, and early puberty. Paternal gene biases, by contrast, may contribute to metabolic disease via lower rates of brown fat thermiogenesis, and through favoring more rapid postnatal catch-up growth after intrauterine growth restriction from environmental causes. These disease risks can be alleviated through dietary and pharmacological alterations that selectively target imprinted gene expression and relevant metabolic pathways. The kinship theory of imprinting, and mother-offspring conflict more generally, provide a clear predictive framework for guiding future research on fetal programming and metabolic disease., (Copyright © 2020 Crespi.)

The first treatments showing effectiveness for some psychiatric disorders, such as lithium for bipolar disorder and chlorpromazine for schizophrenia, were discovered by accident. Currently, psychiatric drug design is seen as a scientific enterprise, limited though it remains by the complexity of brain development and function. Relatively few novel and effective drugs have, however, been developed for many years. The purpose of this article is to demonstrate how evolutionary biology can provide a useful framework for psychiatric drug development. The framework is based on a diametrical nature of autism, compared with psychotic-affective disorders (mainly schizophrenia, bipolar disorder and depression). This paradigm follows from two inferences: (i) risks and phenotypes of human psychiatric disorders derive from phenotypes that have evolved along the human lineage and (ii) biological variation is bidirectional (e.g. higher vs lower, faster vs slower, etc.), such that dysregulation of psychological traits varies in two opposite ways. In this context, the author review the evidence salient to the hypothesis that autism and psychotic-affective disorders represent diametrical disorders in terms of current, proposed and potential psychopharmacological treatments. Studies of brain-derived neurotrophic factor, the PI3K pathway, the NMDA receptor, kynurenic acid metabolism, agmatine metabolism, levels of the endocannabinoid anandamide, antidepressants, anticonvulsants, antipsychotics, and other treatments, demonstrate evidence of diametric effects in autism spectrum disorders and phenotypes compared with psychotic-affective disorders and phenotypes. These findings yield insights into treatment mechanisms and the development of new pharmacological therapies, as well as providing an explanation for the longstanding puzzle of antagonism between epilepsy and psychosis. Lay Summary: Consideration of autism and schizophrenia as caused by opposite alterations to brain development and function leads to novel suggestions for pharmacological treatments.

Prader-Willi and Angelman syndromes are often referred to as a sister pair of neurodevelopmental disorders, resulting from different genetic and epigenetic alterations to the same chromosomal region, 15q11-q13. Some of the primary phenotypes of the two syndromes have been suggested to be opposite to one another, but this hypothesis has yet to be tested comprehensively, and it remains unclear how opposite effects could be produced by changes to different genes in one syndrome compared to the other. We evaluated the evidence for opposite effects on sleep and eating phenotypes in Prader-Willi syndrome and Angelman syndrome, and developed physiological-genetic models that represent hypothesized causes of these differences. Sleep latency shows opposite deviations from controls in Prader-Willi and Angelman syndromes, with shorter latency in Prader-Willi syndrome by meta-analysis and longer latency in Angelman syndrome from previous studies. These differences can be accounted for by the effects of variable gene dosages of UBE3A and MAGEL2, interacting with clock genes, and leading to acceleration (in Prader-Willi syndrome) or deceleration (in Angelman syndrome) of circadian rhythms. Prader-Willi and Angelman syndromes also show evidence of opposite alterations in hyperphagic food selectivity, with more paternally biased subtypes of Angelman syndrome apparently involving increased preference for complementary foods ("baby foods"); hedonic reward from eating may also be increased in Angelman syndrome and decreased in Prader-Willi syndrome. These differences can be explained in part under a model whereby hyperphagia and food selectivity are mediated by the effects of the genes SNORD-116, UBE3A and MAGEL2, with outcomes depending upon the genotypic cause of Angelman syndrome. The diametric variation observed in sleep and eating phenotypes in Prader-Willi and Angelman syndromes is consistent with predictions from the kinship theory of imprinting, reflecting extremes of higher resource demand in Angelman syndrome and lower demand in Prader-Willi syndrome, with a special emphasis on social-attentional demands and attachment associated with bedtime, and feeding demands associated with mother-provided complementary foods compared to offspring-foraged family-type foods., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The author declares no conflict of interest.

The neurohormone oxytocin plays a central role in human social behaviour and cognition, and oxytocin dysregulation may contribute to psychiatric disorders. However, genetic factors influencing individual variation in the oxytocinergic system remain poorly understood. We genotyped 169 healthy adults for a functional polymorphism in GTF2I ( general transcription factor II-I ), a gene associated with high prosociality and reduced social anxiety in Williams syndrome, a condition reported to involve high oxytocin levels and reactivity. Participants' salivary oxytocin levels were measured before and after watching a validated empathy-inducing video. Oxytocin reactivity, defined as pre- to post-video percentage change in salivary oxytocin, varied substantially and significantly between individuals with different GTF2I genotypes, with, additionally, a trend towards an interaction between genotype and sex. Individuals with more oxytocin-reactive genotypes also reported significantly lower social anxiety. These findings suggest a model whereby GTF2I has a continuum of effects on human sociality, from the extreme social phenotypes and oxytocin dysregulation associated with gene deletion in Williams syndrome, to individual differences in oxytocin reactivity and sociality associated with common polymorphisms in healthy populations., (© 2017 The Author(s).)

A suite of recent studies has reported positive genetic correlations between autism risk and measures of mental ability. These findings indicate that alleles for autism overlap broadly with alleles for high intelligence, which appears paradoxical given that autism is characterized, overall, by below-average IQ. This paradox can be resolved under the hypothesis that autism etiology commonly involves enhanced, but imbalanced, components of intelligence. This hypothesis is supported by convergent evidence showing that autism and high IQ share a diverse set of convergent correlates, including large brain size, fast brain growth, increased sensory and visual-spatial abilities, enhanced synaptic functions, increased attentional focus, high socioeconomic status, more deliberative decision-making, profession and occupational interests in engineering and physical sciences, and high levels of positive assortative mating. These findings help to provide an evolutionary basis to understanding autism risk as underlain in part by dysregulation of intelligence, a core human-specific adaptation. In turn, integration of studies on intelligence with studies of autism should provide novel insights into the neurological and genetic causes of high mental abilities, with important implications for cognitive enhancement, artificial intelligence, the relationship of autism with schizophrenia, and the treatment of both autism and intellectual disability.

Tradeoffs centrally mediate the expression of human adaptations. We propose that tradeoffs also influence the prevalence and forms of human maladaptation manifest in disease. By this logic, increased risk for one set of diseases commonly engenders decreased risk for another, diametric, set of diseases. We describe evidence for such diametric sets of diseases from epidemiological, genetic and molecular studies in four clinical domains: (i) psychiatry (autism vs psychotic-affective conditions), (ii) rheumatology (osteoarthritis vs osteoporosis), (iii) oncology and neurology (cancer vs neurodegenerative disorders) and (iv) immunology (autoimmunity vs infectious disease). Diametric disorders are important to recognize because genotypes or environmental factors that increase risk for one set of disorders protect from opposite disorders, thereby providing novel and direct insights into disease causes, prevention and therapy. Ascertaining the mechanisms that underlie disease-related tradeoffs should also indicate means of circumventing or alleviating them, and thus reducing the incidence and impacts of human disease in a more general way., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)

We review the hypothesized and observed effects of two of the major forms of genomic conflicts, genomic imprinting and sexual antagonism, on human health. We focus on phenotypes mediated by peptide and steroid hormones (especially oxytocin and testosterone) because such hormones centrally mediate patterns of physical and behavioral resource allocation that underlie both forms of conflict. In early development, a suite of imprinted genes modulates the human oxytocinergic system as predicted from theory, with paternally inherited gene expression associated with higher oxytocin production, and increased solicitation to mothers by infants. This system is predicted to impact health through the incompatibility of paternal-gene and maternal-gene optima and increased vulnerability of imprinted gene systems to genetic and epigenetic changes. Early alterations to oxytocinergic systems have long-term negative impacts on human psychological health, especially through their effects on attachment and social behavior. In contrast to genomic imprinting, which generates maladaptation along an axis of mother-infant attachment, sexual antagonism is predicted from theory to generate maladaptation along an axis of sexual dimorphism, modulated by steroid and peptide hormones. We describe evidence of sexual antagonism from studies of humans and other animals, demonstrating that sexually antagonistic effects on sex-dimorphic phenotypes, including aspects of immunity, life history, psychology, and behavior, are commonly observed and lead to forms of maladaptation that are demonstrated, or expected, to impact human health. Recent epidemiological and psychiatric studies of schizophrenia in particular indicate that it is mediated, in part, by sexually antagonistic alleles. The primary implication of this review is that data collection focused on (i) effects of imprinted genes that modulate the oxytocin system, and (ii) effects of sexually antagonistic alleles on sex-dimorphic, disease-related phenotypes will lead to novel insights into both human health and the evolutionary dynamics of genomic conflicts.

The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

Background: Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated., Results: We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies., Conclusions: These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.

Imprinted genes have been posited to have important roles in human brain development and cognition, but their effects in nonclinical populations have yet to be investigated. Single-nucleotide polymorphisms (SNPs) of the imprinted gene LRRTM1 have previously been associated with schizophrenia risk and with handedness in individuals with dyslexia. We tested the hypothesis that genetic variation (SNPs) and epigenetic variation (methylation) in this gene are associated with schizotypy and handedness in a nonclinical population. Risk alleles of the three schizophrenia-linked SNPs were associated with significantly and substantially higher levels of total schizotypy. Variation in SNP genotypes was not associated with handedness, but levels of methylation in a block of CpG sites in the putative LRRTM1 promoter region were associated with more-mixed handedness. These findings provide evidence of continuity between schizophrenia and schizotypy with regard to the psychological effects of allelic variation in this imprinted gene, and show that epigenetic variation in an imprinted gene mediates the development and expression of human handedness.

William D. Hamilton postulated the existence of 'genes underlying altruism', under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals.

Background: Individuals commonly prefer certain trait values over others when choosing their mates. If such preferences diverge between populations, they can generate behavioral reproductive isolation and thereby contribute to speciation. Reproductive isolation in insects often involves chemical communication, and cuticular hydrocarbons, in particular, serve as mate recognition signals in many species. We combined data on female cuticular hydrocarbons, interspecific mating propensity, and phylogenetics to evaluate the role of cuticular hydrocarbons in diversification of Timema walking-sticks., Results: Hydrocarbon profiles differed substantially among the nine analyzed species, as well as between partially reproductively-isolated T. cristinae populations adapted to different host plants. In no-choice trials, mating was more likely between species with similar than divergent hydrocarbon profiles, even after correcting for genetic divergences. The macroevolution of hydrocarbon profiles, along a Timema species phylogeny, fits best with a punctuated model of phenotypic change concentrated around speciation events, consistent with change driven by selection during the evolution of reproductive isolation., Conclusion: Altogether, our data indicate that cuticular hydrocarbon profiles vary among Timema species and populations, and that most evolutionary change in hydrocarbon profiles occurs in association with speciation events. Similarities in hydrocarbon profiles between species are correlated with interspecific mating propensities, suggesting a role for cuticular hydrocarbon profiles in mate choice and speciation in the genus Timema.

Environmental shifts and lifestyle changes may result in formerly adaptive traits becoming non-functional or maladaptive. The subsequent decay of such traits highlights the importance of natural selection for adaptations, yet its causes have rarely been investigated. To study the fate of formerly adaptive traits after lifestyle changes, we evaluated sexual traits in five independently derived asexual lineages, including traits that are specific to males and therefore not exposed to selection. At least four of the asexual lineages retained the capacity to produce males that display normal courtship behaviours and are able to fertilize eggs of females from related sexual species. The maintenance of male traits may stem from pleiotropy, or from these traits only regressing via drift, which may require millions of years to generate phenotypic effects. By contrast, we found parallel decay of sexual traits in females. Asexual females produced altered airborne and contact signals, had modified sperm storage organs, and lost the ability to fertilize their eggs, impeding reversals to sexual reproduction. Female sexual traits were decayed even in recently derived asexuals, suggesting that trait changes following the evolution of asexuality, when they occur, proceed rapidly and are driven by selective processes rather than drift.

Both autism spectrum conditions (ASCs) and schizophrenia spectrum conditions (SSCs) involve altered or impaired social and communicative functioning, but whether these shared features indicate overlapping or different etiological factors is unknown. We outline three hypotheses (overlapping, independent, and diametric) for the possible relationship between ASCs and SSCs, and compare their predictions for the expected relationships between autistic and schizotypal phenotypes using the Autism Spectrum Quotient and the Schizotypal Personality Questionnaire-Brief Revised from a large non-clinical sample of undergraduate students. Consistent with previous research, autistic features were positively associated with several schizotypal features, with the most overlap occurring between interpersonal schizotypy and autistic social and communication phenotypes. The first component of a principal components analysis (PCA) of subscale scores reflected these positive correlations, and suggested the presence of an axis (PC1) representing general social interest and aptitude. By contrast, the second principal component (PC2) exhibited a pattern of positive and negative loadings indicative of an axis from autism to positive schizotypy, such that positive schizotypal features loaded in the opposite direction to core autistic features. These overall PCA patterns were replicated in a second data set from a Japanese population. To evaluate the validity of our interpretation of the PCA results, we measured handedness and mental rotation ability, as these are established correlates of SSCs and ASCs, respectively. PC2 scores were significantly associated with hand preference, such that increasingly 'schizotypal' scores predicted reduced strength of handedness, which is consistent with previous research. PC1 scores were positively related to performance on the mental rotation task, suggesting trade-offs between social skills and visual-spatial ability. These results provide novel evidence for an autism-positive schizotypy axis, and highlight the importance of recognizing that psychological variation involving reduced social interest and functioning may have diverse causes.

Variation in polyglutamine repeat number in the androgen receptor (AR CAGn) is negatively correlated with the transcription of androgen-responsive genes and is associated with susceptibility to an extensive list of human disease. Only a small portion of the heritability for many of these diseases is explained by conventional SNP-based genome-wide association studies, and the forces shaping AR CAGn among humans remains largely unexplored. Here, we propose evolutionary models for understanding selection at the AR CAG locus, namely balancing selection, sexual conflict, accumulation-selection, and antagonistic pleiotropy. We evaluate these models by examining AR CAGn-linked susceptibility to eight extensively studied diseases representing the diverse physiological roles of androgens, and consider the costs of these diseases by their frequency and fitness effects. Five diseases could contribute to the distribution of AR CAGn observed among contemporary human populations. With support for disease susceptibilities associated with long and short AR CAGn, balancing selection provides a useful model for studying selection at this locus. Gender-specific differences AR CAGn health effects also support this locus as a candidate for sexual conflict over repeat number. Accompanied by the accumulation of AR CAGn in humans, these models help explain the distribution of repeat number in contemporary human populations.

Plant-feeding insects have undergone unparalleled diversification among different plant taxa, yet explanations for variation in their diversity lack a quantitative, predictive framework. Island biogeographic theory has been applied to spatially discrete habitats but not to habitats, such as host plants, separated by genetic distance. We show that relationships between the diversity of gall-inducing flies and their host plants meet several fundamental predictions from island biogeographic theory. First, plant-taxon genetic distinctiveness, an integrator for long-term evolutionary history of plant lineages, is a significant predictor of variance in the diversity of gall-inducing flies among host-plant taxa. Second, range size and structural complexity also explain significant proportions of the variance in diversity of gall-inducing flies among different host-plant taxa. Third, as with other island systems, plant-lineage age does not predict species diversity. Island biogeographic theory, applied to habitats defined by genetic distance, provides a novel, comprehensive framework for analysing and explaining the diversity of plant-feeding insects and other host-specific taxa.

The interface between evolutionary biology and the biomedical sciences promises to advance understanding of the origins of genetic and infectious diseases in humans, potentially leading to improved medical diagnostics, therapies, and public health practices. The biomedical sciences also provide unparalleled examples for evolutionary biologists to explore. However, gaps persist between evolution and medicine, for historical reasons and because they are often perceived as having disparate goals. Evolutionary biologists have a role in building a bridge between the disciplines by presenting evolutionary biology in the context of human health and medical practice to undergraduates, including premedical and preprofessional students. We suggest that students will find medical examples of evolution engaging. By making the connections between evolution and medicine clear at the undergraduate level, the stage is set for future health providers and biomedical scientists to work productively in this synthetic area. Here, we frame key evolutionary concepts in terms of human health, so that biomedical examples may be more easily incorporated into evolution courses or more specialized courses on evolutionary medicine. Our goal is to aid in building the scientific foundation in evolutionary biology for all students, and to encourage evolutionary biologists to join in the integration of evolution and medicine., (© 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.)

Background: Autism spectrum disorders and schizophrenia have been associated with an overlapping set of copy number variant loci, but the nature and degree of overlap in copy number variants (deletions compared to duplications) between these two disorders remains unclear., Methods: We systematically evaluated three lines of evidence: (1) the statistical bases for associations of autism spectrum disorders and schizophrenia with a set of the primary CNVs thus far investigated, from previous studies; (2) data from case series studies on the occurrence of these CNVs in autism spectrum disorders, especially among children, and (3) data on the extent to which the CNVs were associated with intellectual disability and developmental, speech, or language delays. We also conducted new analyses of existing data on these CNVs in autism by pooling data from seven case control studies., Results: Four of the CNVs considered, dup 1q21.1, dup 15q11-q13, del 16p11.2, and dup 22q11.21, showed clear statistical evidence as autism risk factors, whereas eight CNVs, del 1q21.1, del 3q29, del 15q11.2, del 15q13.3, dup 16p11.2, dup 16p13.1, del 17p12, and del 22q11.21, were strongly statistically supported as risk factors for schizophrenia. Three of the CNVs, dup 1q21.1, dup 16p11.2, and dup 16p13.1, exhibited statistical support as risk factors for both autism and schizophrenia, although for each of these CNVs statistical significance was nominal for tests involving one of the two disorders. For the CNVs that were statistically associated with schizophrenia but were not statistically associated with autism, a notable number of children with the CNVs have been diagnosed with autism or ASD; children with these CNVs also demonstrate a high incidence of intellectual disability and developmental, speech, or language delays., Conclusions: These findings suggest that although CNV loci notably overlap between autism and schizophrenia, the degree of strongly statistically supported overlap in specific CNVs at these loci remains limited. These analyses also suggest that relatively severe premorbidity to CNV-associated schizophrenia in children may sometimes be diagnosed as autism spectrum disorder.

Sexual reproduction is extremely widespread in spite of its presumed costs relative to asexual reproduction, indicating that it must provide significant advantages. One postulated benefit of sex and recombination is that they facilitate the purging of mildly deleterious mutations, which would accumulate in asexual lineages and contribute to their short evolutionary life span. To test this prediction, we estimated the accumulation rate of coding (nonsynonymous) mutations, which are expected to be deleterious, in parts of one mitochondrial (COI) and two nuclear (Actin and Hsp70) genes in six independently derived asexual lineages and related sexual species of Timema stick insects. We found signatures of increased coding mutation accumulation in all six asexual Timema and for each of the three analyzed genes, with 3.6- to 13.4-fold higher rates in the asexuals as compared with the sexuals. In addition, because coding mutations in the asexuals often resulted in considerable hydrophobicity changes at the concerned amino acid positions, coding mutations in the asexuals are likely associated with more strongly deleterious effects than in the sexuals. Our results demonstrate that deleterious mutation accumulation can differentially affect sexual and asexual lineages and support the idea that deleterious mutation accumulation plays an important role in limiting the long-term persistence of all-female lineages.

Autism and schizophrenia are highly heritable neurodevelopmental disorders, each mediated by a diverse suite of genetic and environmental risk factors. Comorbidity and familial aggregation of such neurodevelopmental disorders with other disease-related conditions can provide important insights into their etiology. Epidemiological studies have documented reduced rates of rheumatoid arthritis, a systemic autoimmune condition, in schizophrenia, and recent work has shown increased rates of rheumatoid arthritis in first-degree relatives of autistic individuals, especially mothers. Advances in understanding the genetic basis of rheumatoid arthritis have shown that much of the genetic liability to this condition is due to risk and protective alleles at the HLA DRB1 locus. These data allow robust testing of the hypotheses that allelic variation at DRB1 pleiotropically modulates risk of rheumatoid arthritis, autism and schizophrenia. Systematic review of the literature indicates that reported associations of DRB1 variants with these three conditions are congruent with a pleiotropic model: DRB1*04 alleles have been associated with increased risk of rheumatoid arthritis and autism but decreased risk of schizophrenia, and DRB1*13 alleles have been associated with protection from rheumatoid arthritis and autism but higher risk of schizophrenia. These convergent findings from genetics and epidemiology imply that a subset of autism and schizophrenia cases may be underlain by genetically based neuroimmune alterations, and that analyses of the causes of risk and protective effects from DRB1 variants may provide new approaches to therapy., (© 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.)

Asexuality is rare in animals in spite of its apparent advantage relative to sexual reproduction, indicating that it must be associated with profound costs [1-9]. One expectation is that reproductive advantages gained by new asexual lineages will be quickly eroded over time [3, 5-7]. Ancient asexual taxa that have evolved and adapted without sex would be "scandalous" exceptions to this rule, but it is often difficult to exclude the possibility that putative asexuals deploy some form of "cryptic" sex, or have abandoned sex more recently than estimated from divergence times to sexual relatives [10]. Here we provide evidence, from high intraspecific divergence of mitochondrial sequence and nuclear allele divergence patterns, that several independently derived Timema stick-insect lineages have persisted without recombination for more than a million generations. Nuclear alleles in the asexual lineages displayed significantly higher intraindividual divergences than in related sexual species. In addition, within two asexuals, nuclear allele phylogenies suggested the presence of two clades, with sequences from the same individual appearing in both clades. These data strongly support ancient asexuality in Timema and validate the genus as an exceptional opportunity to attack the question of how asexual reproduction can be maintained over long periods of evolutionary time., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Evolutionary conflicts cause opponents to push increasingly hard and in opposite directions on the regulation of traits. One can see only the intermediate outcome from the balance of the exaggerated and opposed forces. Intermediate expression hides the underlying conflict, potentially misleading one to conclude that trait regulation is designed to achieve efficient and robust expression, rather than arising by the precarious resolution of conflict. Perturbation often reveals the underlying nature of evolutionary conflict. Upon mutation or knockout of one side in the conflict, the other previously hidden and exaggerated push on the trait may cause extreme, pathological expression. In this regard, pathology reveals hidden evolutionary design. We first review several evolutionary conflicts between males and females, including conflicts over mating, fertilization, and the growth rate of offspring. Perturbations of these conflicts lead to infertility, misregulated growth, cancer, behavioral abnormalities, and psychiatric diseases. We then turn to antagonism between the sexes over traits present in both males and females. For many traits, the different sexes favor different phenotypic values, and constraints prevent completely distinct expression in the sexes. In this case of sexual antagonism, we present a theory of conflict between X-linked genes and autosomal genes. We suggest that dysregulation of the exaggerated conflicting forces between the X chromosome and the autosomes may be associated with various pathologies caused by extreme expression along the male-female axis. Rapid evolution of conflicting X-linked and autosomal genes may cause divergence between populations and speciation.

In this review, I describe how evolutionary genomics is uniquely suited to spearhead advances in understanding human disease risk, owing to the privileged position of genes as fundamental causes of phenotypic variation, and the ability of population genetic and phylogenetic methods to robustly infer processes of natural selection, drift, and mutation from genetic variation at the levels of family, population, species, and clade. I first provide an overview of models for the origins and maintenance of genetically based disease risk in humans. I then discuss how analyses of genetic disease risk can be dovetailed with studies of positive and balancing selection, to evaluate the degree to which the 'genes that make us human' also represent the genes that mediate risk of polygenic disease. Finally, I present four basic principles for the nascent field of human evolutionary medical genomics, each of which represents a process that is nonintuitive from a proximate perspective. Joint consideration of these principles compels novel forms of interdisciplinary analyses, most notably studies that (i) analyze tradeoffs at the level of molecular genetics, and (ii) identify genetic variants that are derived in the human lineage or in specific populations, and then compare individuals with derived versus ancestral alleles.

Understanding how new phenotypes evolve is challenging because intermediate stages in transitions from ancestral to derived phenotypes often remain elusive. Here we describe and evaluate a new mechanism facilitating the transition from sexual reproduction to parthenogenesis. In many sexually reproducing species, a small proportion of unfertilized eggs can hatch spontaneously ('tychoparthenogenesis') and develop into females. Using an analytical model, we show that if females are mate-limited, tychoparthenogenesis can result in the loss of males through a positive feedback mechanism whereby tychoparthenogenesis generates female-biased sex ratios and increasing mate limitation. As a result, the strength of selection for tychoparthenogenesis increases in concert with the proportion of tychoparthenogenetic offspring in the sexual population. We then tested the hypothesis that mate limitation selects for tychoparthenogenesis and generates female-biased sex ratios, using data from natural populations of sexually reproducing Timema stick insects. Across 41 populations, both the tychoparthenogenesis rates and the proportions of females increased exponentially as the density of individuals decreased, consistent with the idea that low densities of individuals result in mate limitation and selection for reproductive insurance through tychoparthenogenesis. Our model and data from Timema populations provide evidence for a simple mechanism through which parthenogenesis can evolve rapidly in a sexual population.

The classic evolutionary hypothesis of ecological opportunity proposes that both heterogeneity of resources and freedom from enemies promote phenotypic divergence as a response to increased niche availability. Although phenotypic divergence and speciation have often been inferred to be the primary consequences of the release from competition or predation that accompanies a shift to a new adaptive zone, increased phenotypic variation within species is expected to represent the first stage resulting from such a shift. Using measures of intraspecific morphological variation of 30 species of Galápagos endemic land snails in a phylogenetically controlled framework, we show that the number of local congeners and the number of local plant species are associated with lower and higher intraspecific phenotypic variation, respectively. In this clade, ecological opportunity thus explicitly links the role of competition from congeners and the heterogeneity of resources to the extent of intraspecific phenotypic divergence as adaptive radiation proceeds.

Transitions from sexual reproduction to parthenogenesis may occur along multiple evolutionary pathways and involve various cytological mechanisms to produce diploid eggs. Here, we investigate routes to parthenogenesis in Timema stick insects, a genus comprising five obligate parthenogens. By combining information from microsatellites and karyotypes with a previously published mitochondrial phylogeny, we show that all five parthenogens likely evolved spontaneously from sexually reproducing species, and that the sexual ancestor of one of the five parthenogens was probably of hybrid origin. The complete maintenance of heterozygosity between generations in the five parthenogens strongly suggests that eggs are produced by apomixis. Virgin females of the sexual species were also able to produce parthenogenetic offspring, but these females produced eggs by automixis. High heterozygosity levels stemming from conserved ancestral alleles in the parthenogens suggest, however, that automixis has not generated the current parthenogenetic Timema lineages but that apomixis appeared abruptly in several sexual species. A direct transition from sexual reproduction to (at least functional) apomixis results in a relatively high level of allelic diversity and high efficiency for parthenogenesis. Because both of these traits should positively affect the demographic success of asexual lineages, spontaneous apomixis may have contributed to the origin and maintenance of asexuality in Timema.

Facultative joint colony founding by social insects provides opportunities to analyze the roles of genetic and ecological factors in the evolution of cooperation. Although cooperative nesting is observed in range of social insect taxa, the most detailed studies of this behavior have been conducted with Hymenoptera (ants, bees, and wasps). Here, we show that foundress associations in the haplodiploid social thrips Dunatothrips aneurae (Insecta: Thysanoptera) are most often comprised of close relatives (sisters), though groups with unrelated foundresses are also found. Associations among relatives appear to be facilitated by limited female dispersal, which results in viscous population structure. In addition, we found that per capita productivity declined with increasing group size, sex ratios were female-biased, and some female offspring apparently remained in their natal domicile for some time following eclosion. D. aneurae thus exhibits a suite of similarities with eusocial Hymenoptera, providing evidence for the convergent evolution of associated social and life-history traits in Hymenoptera and Thysanoptera.

Gamete-recognition proteins often evolve rapidly, but it is not known if their divergence occurs within species and corresponds with the evolution of reproductive isolation, or if divergence typically accumulates between already isolated lineages. We examined the evolution of a candidate gamete-recognition protein in several sympatric and allopatric populations of Mytilus blue mussels, species that hybridize in nature. Within a single species, Mytilus galloprovincialis, we found adaptive divergence of Lysin-M7, a sperm acrosomal protein that dissolves the egg vitelline envelope during fertilization. Mytilus galloprovincialis Lysin-M7 alleles group into two distinct clades (termed G and G(D)), and individual alleles in these clades are separated from each other by at least three and up to eleven amino-acid substitutions. Maximum-likelihood estimates of selective pressure (dN/dS =omega) implicate selection in the divergence between M. galloprovincialis Lysin-M7 clades, and within the G(D) clade. Exact tests of population differentiation indicate that the relative frequency of G and G(D) Lysin-M7 alleles differs significantly among M. galloprovincialis populations. Compared with allopatric Mediterranean samples, Lysin-M7 alleles in the G(D) clade are found at elevated frequency in samples from the East Atlantic and California, areas of secondary contact and hybridization between Mytilus species, and Australia, an area of unknown species composition. Adaptive divergence between the alleles most common in allopatry and those found at elevated frequency in samples from sympatry suggests that selection pressures acting in hybridizing populations, likely following Pleistocene secondary contact with M. edulis in the East Atlantic, drove the divergence of Lysin-M7 in M. galloprovincialis.

Speciation of plant-feeding insects is typically associated with host-plant shifts, with subsequent divergent selection and adaptation to the ecological conditions associated with the new plant. However, a few insect groups have apparently undergone speciation while remaining on the same host-plant species, and such radiations may provide novel insights into the causes of adaptive radiation. We used mitochondrial and nuclear DNA to infer a phylogeny for 14 species of gall-inducing Asphondylia flies (Diptera: Cecidomyiidae) found on Larrea tridentata (creosote bush), which have been considered to be monophyletic based on morphological evidence. Our phylogenetic analyses provide strong support for extensive within-host plant speciation in this group, and it demonstrates that diversification has involved numerous shifts between different plant organs (leaves, buds, flowers, and stems) of the same host-plant species. Within-plant speciation of Asphondylia is thus apparently facilitated by the opportunity to partition the plant ecologically. One clade exhibits temporal isolation among species, which may have facilitated divergence via allochronic shifts. Using a novel method based on Bayesian reconstruction, we show that the rate of change in an ecomorphological trait, ovipositor length, was significantly higher along branches with inferred shifts between host-plant organs than along branches without such shifts. This finding suggests that Larrea gall midges exhibit close morphological adaptation to specific host-plant parts, which may mediate ecological transitions via disruptive selection.

Sexual isolation can evolve due to natural selection against hybrids (reinforcement). However, many different forms of hybrid dysfunction, and selective processes that do not involve hybrids, can contribute to the evolution of sexual isolation. Here we review how different selective processes affect the evolution of sexual isolation, describe approaches for distinguishing among them, and assess how they contribute to variation in sexual isolation among populations of Timema cristinae stick-insects. Pairs of allopatric populations of T. cristinae living on different host-plant species exhibit greater sexual isolation than those on the same host, indicating that some sexual isolation has evolved due to host adaptation. Sexual isolation is strongest in regions where populations on different hosts are in geographic contact, a pattern of reproductive character displacement that is indicative of reinforcement. Ecological costs to hybridization do occur but traits under ecological selection (predation) do not co-vary strongly with the probability of between-population mating such that selection on ecological traits is not predicted to produce a strong correlated evolutionary response in mate preference. Moreover, F1 hybrid egg inviability is lacking and the factors contributing to reproductive character displacement require further study. Finally, we show that sexual isolation involves, at least in part, olfactory communication. Our results illustrate how understanding of the evolution of sexual isolation can be enhanced by isolating the roles of diverse ecological and evolutionary processes.

Species richness on island or islandlike systems is a function of colonization, within-island speciation, and extinction. Here we evaluate the relative importance of the first two of these processes as a function of the biogeographical and ecological attributes of islands using the Galápagos endemic land snails of the genus Bulimulus, the most species-rich radiation of these islands. Species in this clade have colonized almost all major islands and are found in five of the six described vegetation zones. We use molecular phylogenetics (based on COI and ITS 1 sequence data) to infer the diversification patterns of extant species of Bulimulus, and multiple regression to investigate the causes of variation among islands in species richness. Maximum-likelihood, Bayesian, and maximum-parsimony analyses yield well-resolved trees with similar topologies. The phylogeny obtained supports the progression rule hypothesis, with species found on older emerged islands connecting at deeper nodes. For all but two island species assemblages we find support for only one or two colonization events, indicating that within-island speciation has an important role in the formation of species on these islands. Even though speciation through colonization is not common, island insularity (distance to nearest major island) is a significant predictor of species richness resulting from interisland colonization alone. However, island insularity has no effect on the overall bulimulid species richness per island. Habitat diversity (measured as plant species diversity), island elevation, and island area, all of which are indirect measures of niche space, are strong predictors of overall bulimulid land snail species richness. Island age is also an important independent predictor of overall species richness, with older islands harboring more species than younger islands. Taken together, our results demonstrate that the diversification of Galápagos bulimulid land snails has been driven by a combination of geographic factors (island age, size, and location), which affect colonization patterns, and ecological factors, such as plant species diversity, that foster within-island speciation.

A central question in evolutionary biology is why animal lineages differ strikingly in rates and patterns of the evolution of reproductive isolation. Here, we show that the maximum genetic distance at which interspecific mammalian pregnancies yield viable neonates is significantly greater in clades with invasive (hemochorial) placentation than in clades with noninvasive (epitheliochorial or endotheliochorial) placentation. Moreover, sister species with invasive placentation exhibit higher allopatry in their geographic ranges, suggesting that formerly separated populations in mammals with this placental type fuse more readily on recontact. These differences are apparently driven by the stronger downregulation of maternal immune responses under invasive placentation, where fetal antigens directly contact the maternal bloodstream. Our results suggest that placental invasiveness mediates a major component of reproductive isolation in mammals.

Adaptive radiation is the evolution of ecological and phenotypic diversity within a rapidly multiplying lineage. Recent studies have identified general patterns in adaptive radiation and inferred that resource competition is a primary factor driving phenotypic divergence. The role and importance of other processes, such as predation, remains controversial. Here we use Timema stick insects to show that adaptive radiation can be driven by divergent selection from visual predators. Ecotypes using different host-plant species satisfy criteria for the early stages of adaptive radiation and differ in quantitative aspects of color, color pattern, body size, and body shape. A manipulative field experiment demonstrates that the direction and strength of divergent selection on these traits is strongly positively correlated with the direction and magnitude of their population divergence in nature but only when selection is estimated in the presence of predation. Our results indicate that both competition and predation may commonly serve as mechanisms of adaptive radiation.

Speciation can involve the evolution of 'cryptic' reproductive isolation that occurs after copulation but before hybrid offspring are produced. Because such cryptic barriers to gene exchange involve post-mating sexual interactions, analyses of their evolution have focused on sexual conflict or traditional sexual selection. Here, we show that ecological divergence between populations of herbivorous walking sticks is integral to the evolution of cryptic reproductive isolation. Low female fitness following between-population mating can reduce gene exchange between populations, thus acting as a form of cryptic isolation. Female walking sticks show reduced oviposition rate and lower lifetime fecundity following between-population versus within-population mating, but only for mating between populations using different host-plant species. Our results indicate that even inherently sexual forms of reproductive isolation can evolve as a by-product of ecological divergence and that post-mating sexual interactions do not necessarily evolve independently of the ecological environment.

Studies of the genetic covariance between habitat preference and performance have reported conflicting outcomes ranging from no covariance to strong covariance. The causes of this variability remain unclear. Here we show that variation in the magnitude of genetic covariance can result from variability in migration regimes. Using data from walking stick insects and a mathematical model, we find that genetic covariance within populations between host plant preference and a trait affecting performance on different hosts (cryptic color pattern) varies in magnitude predictably among populations according to migration regimes. Specifically, genetic covariance within populations is high in heterogeneous habitats where migration between populations locally adapted to different host plants generates nonrandom associations (i.e., linkage disequilibrium) between alleles at color pattern and host preference loci. Conversely, genetic covariance is low in homogeneous habitats where a single host exists and migration between hosts does not occur. Our results show that habitat structure and patterns of migration can strongly affect the evolution and variability of genetic covariance within populations.

We used microsatellite data to estimate levels of inbreeding in four species of solitary gall thrips that are in the same clade as the six species with soldier castes. Three of the four species were highly inbred (Fis 0.54-0.68), and the other apparently mated randomly (Fis near zero). These estimates, combined with previous data from species with soldiers, suggest that inbreeding is a pervasive life-history feature of the gall-inducing thrips on Australian Acacia. Mapping of inbreeding estimates onto the phylogeny of the gall inducers showed that the ancestral lineage that gave rise to soldiers was apparently highly inbred, and therefore, inbreeding could have played a role in the origin of sociality within this group. Moreover, there was a trend from high levels of inbreeding at the origin of soldiers to low levels in the most derived species with soldiers, which exhibits the highest levels of reproductive division of labor and soldier altruism. These patterns are consistent with considerations from population genetics, which show that the likelihood of the origin of soldier altruism is higher in inbreeding populations but that, once soldiers have evolved, a reduction in inbreeding levels may facilitate the evolution of enhanced division of labor and reproductive skew.

Population differentiation often reflects a balance between divergent natural selection and the opportunity for homogenizing gene flow to erode the effects of selection. However, during ecological speciation, trait divergence results in reproductive isolation and becomes a cause, rather than a consequence, of reductions in gene flow. To assess both the causes and the reproductive consequences of morphological differentiation, we examined morphological divergence and sexual isolation among 17 populations of Timema cristinae walking-sticks. Individuals from populations adapted to using Adenostoma as a host plant tended to exhibit smaller overall body size, wide heads, and short legs relative to individuals using Ceonothus as a host. However, there was also significant variation in morphology among populations within host-plant species. Mean trait values for each single population could be reliably predicted based upon host-plant used and the potential for homogenizing gene flow, inferred from the size of the neighboring population using the alternate host and mitochondrial DNA estimates of gene flow. Morphology did not influence the probability of copulation in between-population mating trials. Thus, morphological divergence is facilitated by reductions in gene flow, but does not cause reductions in gene flow via the evolution of sexual isolation. Combined with rearing data indicating that size and shape have a partial genetic basis, evidence for parallel origins of the host-associated forms, and inferences from functional morphology, these results indicate that morphological divergence in T. cristinae reflects a balance between the effects of host-specific natural selection and gene flow. Our findings illustrate how data on mating preferences can help determine the causal associations between trait divergence and levels of gene flow.

Recent years have seen a resurgence of interest in the process of speciation but few studies have elucidated the mechanisms either driving or constraining the evolution of reproductive isolation. In theory, the direct effects of reinforcing selection for increased mating discrimination where interbreeding produces hybrid offspring with low fitness and the indirect effects of adaptation to different environments can both promote speciation. Conversely, high levels of homogenizing gene flow can counteract the forces of selection. We demonstrate the opposing effects of reinforcing selection and gene flow in Timema cristinae walking-stick insects. The magnitude of female mating discrimination against males from other populations is greatest when migration rates between populations adapted to alternate host plants are high enough to allow the evolution of reinforcement, but low enough to prevent gene flow from eroding adaptive divergence in mate choice. Moreover, reproductive isolation is strongest under the combined effects of reinforcement and adaptation to alternate host plants. Our findings demonstrate the joint effects of reinforcement, ecological adaptation and gene flow on progress towards speciation in the wild.

Determining the evolutionary age of asexual lineages should help in inferring the temporal scale under which asexuality and sex evolve and assessing selective factors involved in the evolution of asexuality. We used 416 bp of the mitochondrial COI gene to infer phylogenetic relationships of virtually all known Timema walkingstick species, including extensive intraspecific sampling for all five of the asexuals and their close sexual relatives. The asexuals T. douglasi and T. shepardii were very closely related to each other and evolutionarily young (less than 0.5 million years old). For the asexuals T. monikensis and T. tahoe, evidence for antiquity was weak since only one population of each was sampled, intraspecific divergences were low, and genetic distances to related sexuals were high: maximum-likelihood molecular-clock age estimates ranged from 0.26 to 2.39 million years in T. monikensis and from 0.29-1.06 million years in T. tahoe. By contrast, T. genevieve was inferred to be an ancient asexual, with an age of 0.81 to 1.42 million years. The main correlate of the age of asexual lineages was their geographic position, with younger asexuals being found further north.

Parallel evolution of similar traits in independent populations that inhabit ecologically similar environments strongly implicates natural selection as the cause of evolution. Parallel speciation is a special form of parallel evolution where traits that determine reproductive isolation evolve repeatedly, in closely related populations, as by-products of adaptation to ecological conditions. The outcome of such parallel evolution is that ecologically divergent pairs of populations exhibit greater levels of reproductive isolation than ecologically similar pairs of populations of a similar or younger age. The parallel evolution of reproductive isolation provides strong evidence for natural selection in the process of speciation, but only one conclusive example from nature is known. Populations of the walking-stick insect Timema cristinae that use different host-plant species have diverged in body size and shape, host preference, behaviour and the relative frequency of two highly cryptic colour-pattern morphs. Here we report that divergent selection for host adaptation, and not genetic drift, has promoted the parallel evolution of sexual isolation in this species. Our findings represent a clear demonstration that host-plant adaptation can play a crucial and repeatable role in the early stages of speciation.

The selective pressures involved in the evolution of semelparity and its associated life-history traits are largely unknown. We used species-level analyses, independent contrasts, and reconstruction of ancestral states to study the evolution of body length, fecundity, egg weight, gonadosomatic index, and parity (semelparity vs. degree of iteroparity) in females of 12 species of salmonid fishes. According to both species-level analysis and independent contrasts analysis, body length was positively correlated with fecundity, egg weight, and gonadosomatic index, and semelparous species exhibited a significantly steeper slope for the regression of egg weight on body length than did iteroparous species. Percent repeat breeding (degree of iteroparity) was negatively correlated with gonadosomatic index using independent contrasts analysis. Semelparous species had significantly larger eggs by species-level analysis, and the egg weight contrast for the branch on which semelparity was inferred to have originated was significantly larger than the other egg weight contrasts, corresponding to a remarkable increase in egg weight. Reconstruction of ancestral states showed that egg weight and body length apparently increased with the origin of semelparity, but fecundity and gonadosomatic index remained more or less constant or decreased. Thus, the strong evolutionary linkages between body size, fecundity, and gonadosomatic index were broken during the transition from iteroparity to semelparity. These findings suggest that long-distance migrations, which increase adult mortality between breeding episodes, may have been necessary for the origin of semelparity in Pacific salmon, but that increased egg weight, leading to increased juvenile survivorship, was crucial in driving the transition. Our analyses support the life-history hypotheses that a lower degree of repeat breeding is linked to higher reproductive investment per breeding episode, and that semelparity evolves under a combination of relatively high juvenile survivorship and relatively low adult survivorship.