56. Dinsdale, NL; Crespi, BJ. (2021) Endometriosis and polycystic ovary syndrome are diametric disorders.Evol. Appl. 14: 1693-1715 Endometriosis and polycystic ovary syndrome are diametric disorders
anogenital distance; endometriosis; folliculogenesis; polycystic ovary syndrome; testosterone
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. DOI PubMed
55.Crespi, BJ. (2020) The blind men and the elephant: What is missing cognitively in the study of cumulative technological evolution.Behav. Brain Sci. 43 The blind men and the elephant: What is missing cognitively in the study of cumulative technological evolution
I describe and explain (1) evidence regarding a key role for autism spectrum cognition in human technology; (2) tradeoffs of autistic cognition with social skills; and (3) a model of how cumulative technological culture evolves. This model involves positive feedback whereby increased technical complexity selects for enhanced social learning of mechanistic concepts and skills, leading to further advances in technology. DOI PubMed
54.Crespi, B; Dinsdale, N; Read, S; Hurd, P. (2019) Spirituality, dimensional autism, and schizotypal traits: The search for meaning.PLoS One 14 Spirituality, dimensional autism, and schizotypal traits: The search for meaning
The relationships of spirituality with human social cognition, as exemplified in autism spectrum and schizophrenia spectrum cognitive variation, remain largely unstudied. We quantified non-clinical levels of autism spectrum and schizotypal spectrum traits (using the Autism Quotient and the Schizotypal Personality Questionnaire-Brief Revised) and dimensions of spirituality (using the Hardt Spirituality Questionnaire) in a large sample of undergraduate students. We tested in particular the hypothesis, based on the diametrical model of autism and psychosis, that autism should be negatively associated, and positive schizotypal traits should be positively associated, with spirituality. Our primary findings were threefold. First, in support of the diametric model, total Spirituality score was significantly negatively correlated with total Autism Quotient score, and significantly positively correlated with Positive Schizotypal traits (the Schizotypal Personality Cognitive-Perceptual subscale), as predicted. Second, these associations were driven mainly by opposite patterns regarding the Search for Meaning Spirituality subscale, which was the only subscale that was significantly negatively associated with autism, and significantly positively associated with Positive Schizotypal traits. Third, Belief in God was positively correlated with Positive Schizotypal traits, but was uncorrelated with autism traits. The opposite findings for Search for Meaning can be interpreted in the contexts of well-supported cognitive models for understanding autism in terms of weak central coherence, and understanding Positive Schizotypal traits in terms of enhanced salience. DOI PubMed
53.Crespi, B; Read, S; Hurd, P. (2018) The SETDB2 locus: evidence for a genetic link between handedness and atopic disease.Heredity 120: 77-82 The SETDB2 locus: evidence for a genetic link between handedness and atopic disease
The gene SETDB2, which mediates aspects of laterality in animal model systems, has recently been linked with human handedness as measured continuously on a scale from strong left to strong right. By contrast, it was marginally associated with a left-right dichotomous measure, and it showed no evidence of association with absolute handedness strength independent of direction. We genotyped the SETDB2 handedness-associated single nucleotide polymorphism, rs4942830, in a large healthy population likewise phenotyped for continuous, absolute, and dichotomous handedness variables. Our results demonstrated significant effects of rs4942830 genotype on continuous handedness, and weaker, marginal effects on dichotomous handedness, but no effects on absolute handedness. These results help to establish the locus marked by the SNP rs4942830 as a strong candidate for mediating human handedness. Intriguingly, rs4942830 is also in complete linkage disequilibrium with rs386770867, a polymorphism recently shown to affect human serum levels of IgE production and other atopic phenotypes. These findings implicate this locus in the longstanding links of handedness with asthma and other atopic diseases. DOI
52. Jha, S; Read, S; Hurd, P; Crespi, B. (2018) Segregating polymorphism in the NMDA receptor gene GRIN2A, schizotypy, and mental rotation among healthy individuals.Neuropsychologia 117 Segregating polymorphism in the NMDA receptor gene GRIN2A, schizotypy, and mental rotation among healthy individuals
Schizotypy; Mental rotation; GRIN2A; NMDA receptor; Imagery
Common alleles associated with psychiatric disorders are often regarded as deleterious genes that influence vulnerability to disease, but they may also be considered as mediators of variation in adaptively structured cognitive phenotypes among healthy individuals. The schizophrenia-associated gene GRIN2A (glutamate ionotropic receptor NMDA type subunit 2a) codes for a protein subunit of the NMDA (N-methyl-D-aspartate) receptor that underlies central aspects of human cognition. Pharmacological NMDA blockage recapitulates the major features of schizophrenia in human subjects, and represents a key model for the neurological basis of this disorder. We genotyped two functional GRIN2A polymorphisms in a large population of healthy individuals who were scored for schizotypy and mental imagery/manipulation (the mental rotation test). Rare-allele homozygosity of the promoter microsatellite rs3219790 was associated with high total schizotypy (after adjustment for multiple comparisons) and with enhanced mental rotation ability (nominally, but not after adjustment for multiple comparisons), among males. These findings provide preliminary evidence regarding a genetic basis to previous reports of enhanced mental imagery in schizophrenia and schizotypy. The results also suggest that some schizophrenia-related alleles may be subject to cognitive tradeoffs involving both positive and negative effects on psychological phenotypes, which may help to explain the maintenance of psychiatric-disorder risk alleles in human populations. DOI PubMed
51. Mokkonen, M; Koskela, E; Procyshyn, T; Crespi, B. (2018) Socio-reproductive Conflicts and the Father's Curse Dilemma.Am. Nat. 192 Socio-reproductive Conflicts and the Father's Curse Dilemma
genomic conflict; sexual conflict; parent-offspring conflict; testosterone; oxytocin; bank vole
Evolutionary conflicts between males and females can manifest over sexually antagonistic interactions at loci or over sexually antagonistic interests within a locus. The latter form of conflict, intralocus sexual conflict, arises from sexually antagonistic selection and constrains the fitness of individuals through a phenotypic compromise. These conflicts, and socio-reproductive interactions in general, are commonly mediated by hormones, and thus predictive insights can be gained from studying their mediating effects. Here, we integrate several lines of evidence to describe a novel, hormonally mediated reproductive dilemma that we call the father's curse, which results from an intralocus conflict between mating and parental efforts. Essentially, a genetic locus exerts pleiotropic and antagonistic effects on the mating effort of one individual and the parental effort of a related individual who is the primary provider of parental care. We outline the criteria for operation of the father's curse dilemma, provide evidence of the phenomenon, and discuss the predictions and outcomes arising from its dynamics. By integrating the effects of hormones into socio-reproductive conflicts and socio-reproductive effort, clearer links between genotypes, phenotypes, and fitness can be established. DOI PubMed
50. Nosil, P; Villoutreix, R; de Carvalho, CF; Farkas, TE; Soria-Carrasco, V; Feder, JL; Crespi, BJ; Gompert, Z. (2018) Natural selection and the predictability of evolution in Timema stick insects.Science 359: 765-770 Natural selection and the predictability of evolution in Timema stick insects
Predicting evolution remains difficult. We studied the evolution of cryptic body coloration and pattern in a stick insect using 25 years of field data, experiments, and genomics. We found that evolution is more difficult to predict when it involves a balance between multiple selective factors and uncertainty in environmental conditions than when it involves feedback loops that cause consistent back-and-forth fluctuations. Specifically, changes in color-morph frequencies are modestly predictable through time (r(2) = 0.14) and driven by complex selective regimes and yearly fluctuations in climate. In contrast, temporal changes in pattern-morph frequencies are highly predictable due to negative frequency-dependent selection (r(2) = 0.86). For both traits, however, natural selection drives evolution around a dynamic equilibrium, providing some predictability to the process. DOI PubMed
48.Crespi, BJ; Procyshyn, TL. (2017) Williams syndrome deletions and duplications: Genetic windows to understanding anxiety, sociality, autism, and schizophrenia.Neurosci. Biobehav. Rev. 79: 14-26 Williams syndrome deletions and duplications: Genetic windows to understanding anxiety, sociality, autism, and schizophrenia
Williams syndrome; Prosociality; Anxiety; Oxytocin; Autism; Schizophrenia
We describe and evaluate an integrative hypothesis for helping to explain the major neurocognitive features of individuals with Williams syndrome region deletions and duplications. First, we demonstrate how the cognitive differences between Williams syndrome individuals, individuals with duplications of this region, and healthy individuals parallel the differences between individuals subject to effects of increased or decreased oxytocin. Second, we synthesize evidence showing that variation in expression of the gene GTF2I (General Transcription Factor II-I) underlies the primary social phenotypes of Williams syndrome and that common genetic variation in GTF2I mediates oxytocin reactivity, and its correlates, in healthy populations. Third, we describe findings relevant to the hypothesis that the GTF2I gene is subject to parent of origin effects whose behavioral expression fits with predictions from the kinship theory of genomic imprinting. Fourth, we describe how Williams syndrome can be considered, in part, as an autistic syndrome of Lorna Wing's 'active-but-odd' autism subtype, in contrast to associations of duplications with both schizophrenia and autism. DOI
47. Riesch, R; Muschick, M; Lindtke, D; Villoutreix, R; Comeault, AA; Farkas, TE; Lucek, K; Hellen, E; Soria-Carrasco, V; Dennis, SR; de Carvalho, CF; Safran, RJ; Sandoval, CP; Feder, J; Gries, R; Crespi, BJ; Gries, G; Gompert, Z; Nosil, P. (2017) Transitions between phases of genomic differentiation during stick-insect speciation.Nature Ecology & Evolution 1 Transitions between phases of genomic differentiation during stick-insect speciation
Speciation can involve a transition from a few genetic loci that are resistant to gene flow to genome-wide differentiation. However, only limited data exist concerning this transition and the factors promoting it. Here, we study phases of speciation using data from >100 populations of 11 species of Timema stick insects. Consistent with early phases of genie speciation, adaptive colour-pattern loci reside in localized genetic regions of accentuated differentiation between populations experiencing gene flow. Transitions to genome-wide differentiation are also observed with gene flow, in association with differentiation in polygenic chemical traits affecting mate choice. Thus, intermediate phases of speciation are associated with genome-wide differentiation and mate choice, but not growth of a few genomic islands. We also find a gap in genomic differentiation between sympatric taxa that still exchange genes and those that do not, highlighting the association between differentiation and complete reproductive isolation. Our results suggest that substantial progress towards speciation may involve the alignment of multi-faceted aspects of differentiation. DOI
46.Crespi, BJ. (2016) Oxytocin, testosterone, and human social cognition.Biological Reviews 91: 390-408 Oxytocin, testosterone, and human social cognition
oxytocin; testosterone; social cognition; autism; schizophrenia; depression
I describe an integrative social-evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co-opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness-enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness-reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self-oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under-developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively 'hyper-developed' social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint effects partially mediate risks and phenotypes of autism and psychotic-affective conditions. These considerations have direct implications for the development of therapies for alleviating disorders of social cognition, and for understanding how such disorders are associated with the evolution of human cognitive-affective architecture. DOI
45.Crespi, BJ. (2016) The convergent and divergent evolution of social-behavioral economics.Behavioral and Brain Sciences 39 The convergent and divergent evolution of social-behavioral economics
Human hunter-gatherers share a suite of traits with social insects, which demonstrates convergent social evolution of these taxa prior to agriculture. Humans differ from social insects in that their divisions of labor are more competitive than cooperative. Resulting higher within-group competition in humans has been alleviated by religion and culturally imposed monogamy, both of which also find parallels among social insects. DOI
44. Robinson, KJ; Hurd, PL; Read, S; Crespi, BJ. (2016) The PCSK6 gene is associated with handedness, the autism spectrum, and magical ideation in a non-clinical population.Neuropsychologia 84: 205-212 The PCSK6 gene is associated with handedness, the autism spectrum, and magical ideation in a non-clinical population
Handedness; Lateralization; PCSK6 gene; VNTR; Autism; Schizotypy
Common polymorphisms in the gene PCSK6, whose protein product mediates the development of brain and body asymmetry through the NODAL pathway, have recently been associated with handedness in three studies, making it a key candidate gene for understanding the developmental and expression of human lateralization. We tested the hypothesis that the PCSK6 VNTR polymorphism rs1053972 influences the expression of handedness and aspects of dimensional schizotypy and autism. For a sample of 709 healthy individuals, rs1053972 genotype was significantly associated with categorical measures of handedness, and with dimensional handedness in subsets of the population with high schizotypy and magical ideation or a lack of strong right-handedness. Both findings showed evidence of stronger or exclusive effects among females, compared to males. Genotypes of PCSK6 also showed significant sex limited associations with magical ideation, a component of positive schizotypal cognition measured using the Schizotypal Personality Questionnaire, and total autism score, measured using the Autism Spectrum Quotient. These results partially replicate previous studies on effects of PCSK6 rs1053972 genetic variation on handedness phenotypes, link the PCSK6 gene with the dimensional expression of neurodevelopmental conditions in healthy individuals, and show that associations of this gene with handedness and psychological phenotypes exhibit evidence of sex-limited effects. (C) 2016 Elsevier Ltd. All rights reserved. DOI PubMed
43. Arbuthnott, D; Crespi, BJ; Schwander, T. (2015) Female Stick Insects Mate Multiply to Find Compatible Mates.American Naturalist 186: 519-530 Female Stick Insects Mate Multiply to Find Compatible Mates
polyandry; mate choice; genetic compatibility; sexual selection; phasmid
Why females of many species mate multiply in the absence of direct benefits remains an open question in evolutionary ecology. Interacting and mating with multiple males can be costly to females in terms of time, resources, predation risk, and disease transmission. A number of indirect genetic benefits have been proposed to explain such behaviors, but the relative importance of these mechanisms in natural systems remains unclear. We tested for several direct and indirect benefits of polyandry in the walking stick Timema cristinae. We found no evidence of direct benefits with respect to longevity or fecundity. However, male x female genotypic interactions affected egg-hatching success and offspring production independent of relatedness, suggesting that mating with certain males benefits females and that the best male may differ for each female. Furthermore, multiply mated females biased paternity toward one or few males, and the extent of this bias was positively correlated to egg-hatching success. Our data, therefore, provide evidence for indirect benefits through compatibility effects in this species. By mating multiply, females may improve their chances of mating with a compatible male if compatibility cannot be assessed before mating. Such compatibility effects can explain the evolution and maintenance of polyandry in Timema and many other species. DOI
42. Arnal, A; Ujvari, B; Crespi, B; Gatenby, RA; Tissot, T; Vittecoq, M; Ewald, PW; Casali, A; Ducasse, H; Jacqueline, C; Misse, D; Renaud, F; Roche, B; Thomas, F. (2015) Evolutionary perspective of cancer: myth, metaphors, and reality.Evolutionary Applications 8: 541-544 Evolutionary perspective of cancer: myth, metaphors, and reality
adaptationism; cancer; evolutionary processes
The evolutionary perspective of cancer (which origins and dynamics result from evolutionary processes) has gained significant international recognition over the past decade and generated a wave of enthusiasm among researchers. In this context, several authors proposed that insights into evolutionary and adaptation dynamics of cancers can be gained by studying the evolutionary strategies of organisms. Although this reasoning is fundamentally correct, in our opinion, it contains a potential risk of excessive adaptationism, potentially leading to the suggestion of complex adaptations that are unlikely to evolve among cancerous cells. For example, the ability of recognizing related conspecifics and adjusting accordingly behaviors as in certain free-living species appears unlikely in cancer. Indeed, despite their rapid evolutionary rate, malignant cells are under selective pressures for their altered lifestyle for only few decades. In addition, even though cancer cells can theoretically display highly sophisticated adaptive responses, it would be crucial to determine the frequency of their occurrence in patients with cancer, before therapeutic applications can be considered. Scientists who try to explain oncogenesis will need in the future to critically evaluate the metaphorical comparison of selective processes affecting cancerous cells with those affecting organisms. This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications. DOI
41.Crespi, BJ. (2015) Cognitive trade-offs and the costs of resilience.Behavioral and Brain Sciences 38 Cognitive trade-offs and the costs of resilience
Genetic, endocrinological, and psychological evidence demonstrates that resilience commonly trades off with sensitivity. The existence of such trade-offs indicates that resilience bears costs as well as benefits, and that some disorders can best be conceptualized in terms of extremes of trade-offs rather than expression of deficits. Testing for cognitive trade-offs should be a priority for psychiatry, psychology, neuroscience, and genetics. DOI
40. Elliot, MG; Crespi, BJ. (2015) Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals.Philosophical Transactions of the Royal Society B-Biological Sciences 370 Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals
placentation; pre-eclampsia; positive selection; candidate genes; Darwinian medicine
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. DOI PubMed
39. Mokkonen, M; Crespi, BJ. (2015) Genomic conflicts and sexual antagonism in human health: insights from oxytocin and testosterone.Evolutionary Applications 8: 307-325 Genomic conflicts and sexual antagonism in human health: insights from oxytocin and testosterone
genomic imprinting; kinship theory; parental antagonism; parent-offspring conflict; sexual antagonism; sexual conflict
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. DOI PubMed
38.Crespi, B. (2013) Diametric gene-dosage effects as windows into neurogenetic architecture.Current Opinion in Neurobiology 23: 143-151 Diametric gene-dosage effects as windows into neurogenetic architecture
17Q21.31 MICRODELETION SYNDROME; PRADER-WILLI-SYNDROME; BEHAVIORAL PHENOTYPES; BIPOLAR DISORDER; UP-REGULATION; KANSL1 CAUSE; AUTISM; SCHIZOPHRENIA; MICE; 16P11.2
Gene expression can be modulated in two opposite directions, towards higher or lower amounts of product. How do diametric changes in gene dosage influence neurological development and function? Recent studies of transgenic and knockout mouse models, genomic copy-number variants, imprinted-gene expression alterations, and sex-chromosome aneuploidies are revealing examples of 'mirror-extreme' brain and behavior phenotypes, which provide unique insights into neurodevelopmental architecture. These convergent studies quantitatively connect gene dosages with specific trajectories and outcomes, with important implications for the experimental dissection of normal neurological functions, the genetic analysis of psychiatric disorders, the development of pharmacological therapies, and mechanisms for the evolution of human brain and behavior. DOI
37.Crespi, B; Nosil, P. (2013) Conflictual speciation: species formation via genomic conflict.Trends in Ecology & Evolution 28: 48-57 Conflictual speciation: species formation via genomic conflict
SELFISH GENETIC ELEMENTS; HYBRID MALE-STERILITY; FEMALE MEIOTIC DRIVE; REPRODUCTIVE ISOLATION; TRANSPOSABLE ELEMENTS; X-CHROMOSOME; DROSOPHILA-MELANOGASTER; ECOLOGICAL SPECIATION; SEXUAL-DIMORPHISM; FLOWERING PLANTS
A remarkable suite of forms of genomic conflict has recently been implicated in speciation. We propose that these diverse roles of genomic conflict in speciation processes can be unified using the concept of 'conflictual speciation'. Conflictual speciation centers on the evolution of reproductive isolation as a byproduct of antagonistic selection among genomic elements with divergent fitness interests. Intragenomic conflicts are expected to readily generate Dobzhansky-Muller incompatibilities, due to population-specific interactions between opposing elements, and thus they could be especially important in speciation. Moreover, selection from genomic conflicts should be relatively unrelenting across ecological and evolutionary time scales. We explain how intra-genomic conflicts can promote, or sometimes constrain, speciation, and describe evidence relating conflicts to the evolution of reproductive isolation. DOI
36. Crosley, EJ; Elliot, MG; Christians, JK; Crespi, BJ. (2013) Placental invasion, preeclampsia risk and adaptive molecular evolution at the origin of the great apes: Evidence from genome-wide analyses.Placenta 34: 127-132 Placental invasion, preeclampsia risk and adaptive molecular evolution at the origin of the great apes: Evidence from genome-wide analyses
DEEP TROPHOBLAST INVASION; MATRIX-METALLOPROTEINASES; NONHUMAN-PRIMATES; INSULIN-RECEPTORS; LOWLAND GORILLA; GENE-EXPRESSION; CELL INVASION; ACTIVIN-A; PREGNANCY; INHIBIN
Introduction: Recent evidence from chimpanzees and gorillas has raised doubts that preeclampsia is a uniquely human disease. The deep extravillous trophoblast (EVT) invasion and spiral artery remodeling that characterizes our placenta (and is abnormal in preeclampsia) is shared within great apes, setting Homininae apart from Hylobatidae and Old World Monkeys, which show much shallower trophoblast invasion and limited spiral artery remodeling. We hypothesize that the evolution of a more invasive placenta in the lineage ancestral to the great apes involved positive selection on genes crucial to EVT invasion and spiral artery remodeling. Furthermore, identification of placentally-expressed genes under selection in this lineage may identify novel genes involved in placental development. Methods: We tested for positive selection in approximately 18,000 genes using the ratio of non-synonymous to synonymous amino acid substitution for protein-coding DNA. DAVID Bioinformatics Resources identified biological processes enriched in positively selected genes, including processes related to EVT invasion and spiral artery remodeling. Results: Analyses revealed 295 and 264 genes under significant positive selection on the branches ancestral to Hominidae (Human, Chimp, Gorilla, Orangutan) and Homininae (Human, Chimp, Gorilla), respectively. Gene ontology analysis of these gene sets demonstrated significant enrichments for several functional gene clusters relevant to preeclampsia risk, and sets of placentally-expressed genes that have been linked with preeclampsia and/or trophoblast invasion in other studies. Conclusion: Our study represents a novel approach to the identification of candidate genes and amino acid residues involved in placental pathologies by implicating them in the evolution of highly-invasive placenta. (C) 2012 Elsevier Ltd. All rights reserved. DOI
35. Dinsdale, NL; Hurd, PL; Wakabayashi, A; Elliot, M; Crespi, BJ. (2013) How Are Autism and Schizotypy Related? Evidence from a Non-Clinical Population.PLOS One 8 How Are Autism and Schizotypy Related? Evidence from a Non-Clinical Population
SPECTRUM QUOTIENT AQ; HIGH-FUNCTIONING AUTISM; GENERAL-POPULATION; MAGICAL IDEATION; MIXED-HANDEDNESS; HAND PREFERENCE; SEX-DIFFERENCES; SOCIAL BRAIN; SCHIZOPHRENIA; DISORDERS
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. DOI
34. Konefal, S; Elliot, M; Crespi, B. (2013) The adaptive significance of adult neurogenesis: an integrative approach.Frontiers in Neuroanatomy 7 The adaptive significance of adult neurogenesis: an integrative approach
LONG-TERM POTENTIATION; NEURAL STEM-CELLS; GENERATED GRANULE CELLS; ENHANCED SYNAPTIC PLASTICITY; BORN HIPPOCAMPAL-NEURONS; OLFACTORY-BULB NEURONS; DENTATE GYRUS; PATTERN SEPARATION; ENTORHINAL CORTEX; NEWBORN NEURONS
Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structural by ecologically and socially relevant selective contexts. DOI
33. Ryan, CP; Crespi, BJ. (2013) Androgen receptor polyglutamine repeat number: models of selection and disease susceptibility.Evolutionary Applications 6: 180-196 Androgen receptor polyglutamine repeat number: models of selection and disease susceptibility
PROSTATE-CANCER RISK; BULBAR MUSCULAR-ATROPHY; GENE CAG REPEAT; SIMPLE SEQUENCE REPEATS; CORONARY-ARTERY-DISEASE; BONE-MINERAL DENSITY; ACID TANDEM REPEATS; HUMAN BREAST-CANCER; MALE-INFERTILITY; PERSONALITY-TRAITS
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. DOI
32. Schwander, T; Arbuthnott, D; Gries, R; Gries, G; Nosil, P; Crespi, BJ. (2013) Hydrocarbon divergence and reproductive isolation in Timema stick insects.BMC Evolutionary Biology 13 Hydrocarbon divergence and reproductive isolation in Timema stick insects
HOST-PLANT ADAPTATION; CRISTINAE WALKING-STICKS; MALE MATE CHOICE; CUTICULAR HYDROCARBONS; SEXUAL SELECTION; DROSOPHILA-MOJAVENSIS; MORPHOLOGICAL EVOLUTION; CACTOPHILIC DROSOPHILA; INCIPIENT SPECIATION; MATING PREFERENCES
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. DOI
31. Schwander, T; Crespi, BJ; Gries, R; Gries, G. (2013) Neutral and selection-driven decay of sexual traits in asexual stick insects.Proceedings of the Royal Society B-Biological Sciences 280 Neutral and selection-driven decay of sexual traits in asexual stick insects
TIMEMA WALKING-STICKS; WOLBACHIA-INDUCED PARTHENOGENESIS; LEPTOPILINA-CLAVIPES HYMENOPTERA; EVOLUTION; REPRODUCTION; ANCIENT; VESTIGIALIZATION; PHYLOGENETICS; PARASITOIDS; APHELINIDAE
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. DOI
30. Stencel, A; Crespi, B. (2013) What is a genome?Molecular Ecology 22: 3437-3443 What is a genome?
HORIZONTAL GENE-TRANSFER; TRANSPOSABLE ELEMENTS; EVOLUTION; CHROMOSOME; HISTORY; ENCODE; DNA; INTROGRESSION; DIVERSITY; SEQUENCES
The field of genomics is expanding rapidly, yet the meanings of the word genome' have yet to be conceptualized in explicit, coherent and useful frameworks. We develop and apply an evolutionary conceptualization of the genome, which represents a logical extension of the evolutionary definition of a gene developed by George C. Williams. An evolutionary genome thus represents a set of genetic material, in a lineage, that due to common interests tends to favour the same or similar phenotypes. This conceptualization provides novel perspectives on genome functions, boundaries and evolution, which should help to guide theoretical and empirical genomics research. DOI
29. Antolin, MF; Jenkins, KP; Bergstrom, CT; Crespi, BJ; De, S; Hancock, A; Hanley, KA; Meagher, TR; Moreno-Estrada, A; Nesse, RM; Omenn, GS; Stearns, SC. (2012) EVOLUTION AND MEDICINE IN UNDERGRADUATE EDUCATION: A PRESCRIPTION FOR ALL BIOLOGY STUDENTS.Evolution 66: 1991-2006 EVOLUTION AND MEDICINE IN UNDERGRADUATE EDUCATION: A PRESCRIPTION FOR ALL BIOLOGY STUDENTS
Biomedical research; evolution of disease; host-pathogen interactions; human genetics; medical practice; mismatch hypothesis; premedical curriculum; public health; science education
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. DOI
28.Crespi, B; Schwander, T. (2012) Asexual evolution: do intragenomic parasites maintain sex?Molecular Ecology 21: 3893-3895 Asexual evolution: do intragenomic parasites maintain sex?
adaptation; animal mating; breeding systems; ecological genetics; evolution of sex
Resolving the paradox of sex, with its twofold cost to genic transmission, remains one of the major unresolved questions in evolutionary biology. Counting this genetic cost has now gone genomic. In this issue of Molecular Ecology, Kraaijeveld (2012) describe the first genome-scale comparative study of related sexual and asexual animal lineages, to test the hypothesis that asexuals bear heavier loads of deleterious transposable elements. A much higher density of such parasites might be expected, due to the inability of asexual lineages to purge transposons via mechanisms exclusive to sexual reproduction. They find that the answer is yesand nodepending upon the family of transposons considered. Like many such advances in testing theory, more questions are raised by this study than answered, but a door has been opened to molecular evolutionary analyses of how responses to selection from intragenomic parasites might mediate the costs of sex. DOI
26. Henry, L; Schwander, T; Crespi, BJ. (2012) Deleterious Mutation Accumulation in Asexual Timema Stick Insects.Molecular Biology and Evolution 29: 401-408 Deleterious Mutation Accumulation in Asexual Timema Stick Insects
CYTOCHROME-OXIDASE-I; FRESH-WATER SNAIL; SEXUAL REPRODUCTION; ANCIENT ASEXUALITY; BDELLOID ROTIFERS; EVOLUTION; SELECTION; PATTERNS; PARTHENOGENESIS; RECOMBINATION
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. DOI
25. Joy, JB; Crespi, BJ. (2012) Island phytophagy: explaining the remarkable diversity of plant-feeding insects.Proceedings of the Royal Society B-Biological Sciences 279: 3250-3255 Island phytophagy: explaining the remarkable diversity of plant-feeding insects
macroevolution; plant-insect interactions; diversification; island biogeography; plant genetic distinctiveness; insularity
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. DOI
23.Crespi, B. (2011) The evolutionary biology of child health.Proceedings of the Royal Society B-Biological Sciences 278: 1441-1449 The evolutionary biology of child health
evolutionary medicine; child health; cancer; growth
I apply evolutionary perspectives and conceptual tools to analyse central issues underlying child health, with emphases on the roles of human-specific adaptations and genomic conflicts in physical growth and development. Evidence from comparative primatology, anthropology, physiology and human disorders indicates that child health risks have evolved in the context of evolutionary changes, along the human lineage, affecting the timing, growth-differentiation phenotypes and adaptive significance of prenatal stages, infancy, childhood, juvenility and adolescence. The most striking evolutionary changes in humans are earlier weaning and prolonged subsequent pre-adult stages, which have structured and potentiated maladaptations related to growth and development. Data from human genetic and epigenetic studies, and mouse models, indicate that growth, development and behaviour during pre-adult stages are mediated to a notable degree by effects from genomic conflicts and imprinted genes. The incidence of cancer, the primary cause of non-infectious childhood mortality, mirrors child growth rates from birth to adolescence, with paediatric cancer development impacted by imprinted genes that control aspects of growth. Understanding the adaptive significance of child growth and development phenotypes, in the context of human-evolutionary changes and genomic conflicts, provides novel insights into the causes of disease in childhood. DOI
22. Frank, SA; Crespi, BJ. (2011) Pathology from evolutionary conflict, with a theory of X chromosome versus autosome conflict over sexually antagonistic traits.Proceedings of the National Academy of Sciences of the United States of America 108: 10886-10893 Pathology from evolutionary conflict, with a theory of X chromosome versus autosome conflict over sexually antagonistic traits
BECKWITH-WIEDEMANN-SYNDROME; PRADER-WILLI-SYNDROME; SILVER-RUSSELL-SYNDROME; ANGELMAN-SYNDROME; TUMOR RISK; PARENTAL ANTAGONISM; GENE-EXPRESSION; BIRTH-WEIGHT; FETAL-GROWTH; SELECTION
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. DOI
21. Schwander, T; Henry, L; Crespi, BJ. (2011) Molecular Evidence for Ancient Asexuality in Timema Stick Insects.Current Biology 21: 1129-1134 Molecular Evidence for Ancient Asexuality in Timema Stick Insects
SEXUAL REPRODUCTION; BDELLOID ROTIFERS; HYBRID ORIGINS; DNA-SEQUENCES; EVOLUTION; RECOMBINATION; POPULATION; LINEAGES; PARTHENOGENESIS; PATTERNS
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. DOI
20. Springer, SA; Crespi, BJ; Swanson, WJ. (2011) Beyond the phenotypic gambit: molecular behavioural ecology and the evolution of genetic architecture.Molecular Ecology 20: 2240-2257 Beyond the phenotypic gambit: molecular behavioural ecology and the evolution of genetic architecture
adaptation; behaviour; social evolution; evolutionary conflict; genetic architecture
Most studies of behaviour examine traits whose proximate causes include sensory input and neural decision-making, but conflict and collaboration in biological systems began long before brains or sensory systems evolved. Many behaviours result from non-neural mechanisms such as direct physical contact between recognition proteins or modifications of development that coincide with altered behaviour. These simple molecular mechanisms form the basis of important biological functions and can enact organismal interactions that are as subtle, strategic and interesting as any. The genetic changes that underlie divergent molecular behaviours are often targets of selection, indicating that their functional variation has important fitness consequences. These behaviours evolve by discrete units of quantifiable phenotypic effect (amino acid and regulatory mutations, often by successive mutations of the same gene), so the role of selection in shaping evolutionary change can be evaluated on the scale at which heritable phenotypic variation originates. We describe experimental strategies for finding genes that underlie biochemical and developmental alterations of behaviour, survey the existing literature highlighting cases where the simplicity of molecular behaviours has allowed insight to the evolutionary process and discuss the utility of a genetic knowledge of the sources and spectrum of phenotypic variation for a deeper understanding of how genetic and phenotypic architectures evolve. DOI
19.Crespi, B; Stead, P; Elliot, M. (2010) Comparative genomics of autism and schizophrenia.Proceedings of the National Academy of Sciences of the United States of America 107: 1736-1741 Comparative genomics of autism and schizophrenia
genetics; evolution; psychiatry
We used data from studies of copy-number variants (CNVs), single-gene associations, growth-signaling pathways, and intermediate phenotypes associated with brain growth to evaluate four alternative hypotheses for the genomic and developmental relationships between autism and schizophrenia: (i) autism subsumed in schizophrenia, (ii) independence, (iii) diametric, and (iv) partial overlap. Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other. Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance. However, differentiation between the partial overlap and diametric hypotheses using these data is precluded by limited overlap in the specific genetic markers analyzed in both autism and schizophrenia. Evidence from the effects of risk variants on growth-signaling pathways shows that autism-spectrum conditions tend to be associated with up-regulation of pathways due to loss of function mutations in negative regulators, whereas schizophrenia is associated with reduced pathway activation. Finally, data from studies of head and brain size phenotypes indicate that autism is commonly associated with developmentally-enhanced brain growth, whereas schizophrenia is characterized, on average, by reduced brain growth. These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurodevelopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain. DOI
18.Crespi, B; Summers, K; Dorus, S. (2010) Evolutionary genomics of human intellectual disability.Evolutionary Applications 3: 52-63 Evolutionary genomics of human intellectual disability
LINKED MENTAL-RETARDATION; NIJMEGEN-BREAKAGE-SYNDROME; AARSKOG-SCOTT-SYNDROME; REGULATING BRAIN SIZE; RHO-FAMILY GTPASES; FRAGILE-X-SYNDROME; POSITIVE SELECTION; DNA-DAMAGE; ADAPTIVE EVOLUTION; COGNITIVE-ABILITY
Previous studies have postulated that X-linked and autosomal genes underlying human intellectual disability may have also mediated the evolution of human cognition. We have conducted the first comprehensive assessment of the extent and patterns of positive Darwinian selection on intellectual disability genes in humans. We report three main findings. First, as noted in some previous reports, intellectual disability genes with primary functions in the central nervous system exhibit a significant concentration to the X chromosome. Second, there was no evidence for a higher incidence of recent positive selection on X-linked than autosomal intellectual disability genes, nor was there a higher incidence of selection on such genes overall, compared to sets of control genes. However, the X-linked intellectual disability genes inferred to be subject to recent positive selection were concentrated in the Rho GTP-ase pathway, a key signaling pathway in neural development and function. Third, among all intellectual disability genes, there was evidence for a higher incidence of recent positive selection on genes involved in DNA repair, but not for genes involved in other functions. These results provide evidence that alterations to genes in the Rho GTP-ase and DNA-repair pathways may play especially-important roles in the evolution of human cognition and vulnerability to genetically-based intellectual disability. DOI
16. Schwander, T; Vuilleumier, S; Dubman, J; Crespi, BJ. (2010) Positive feedback in the transition from sexual reproduction to parthenogenesis.Proceedings of the Royal Society B-Biological Sciences 277: 1435-1442 Positive feedback in the transition from sexual reproduction to parthenogenesis
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. DOI
15. Summers, K; Crespi, BJ. (2010) Xmrks the spot: life history tradeoffs, sexual selection and the evolutionary ecology of oncogenesis.Molecular Ecology 19: 3022-3024 Xmrks the spot: life history tradeoffs, sexual selection and the evolutionary ecology of oncogenesis
In a classic paper, George Williams (1957) argued that alleles promoting reproductive success early in life may be favoured by selection, even if they reduce the lifespan of individuals that bear the allele. A variety of evidence supports the theory that such 'antagonistic pleiotropy' is a major factor contributing to the evolution of senescence (Ljubuncic & Reznick 2009), but examples of specific alleles known to fulfil Williams' criteria remain rare, in both humans and other animals (e.g. Alexander et al. 2007; Kulminski et al. 2010). An intriguing example in this issue of Molecular Ecology (Fernandez & Bowser 2010) demonstrates that both natural and sexual selection may favour melanoma-promoting oncogene alleles in the fish genus Xiphophorus. DOI
14.Crespi, B. (2009) Gender, biology, and mathematics performance.Proceedings of the National Academy of Sciences of the United States of America 106: E102-E102 Gender, biology, and mathematics performance
DOI
13. Schwander, T; Crespi, BJ. (2009) MULTIPLE DIRECT TRANSITIONS FROM SEXUAL REPRODUCTION TO APOMICTIC PARTHENOGENESIS IN TIMEMA STICK INSECTS.Evolution 63: 84-103 MULTIPLE DIRECT TRANSITIONS FROM SEXUAL REPRODUCTION TO APOMICTIC PARTHENOGENESIS IN TIMEMA STICK INSECTS
CRISTINAE WALKING-STICKS; DROSOPHILA-MERCATORUM; PHYLOGENETIC-RELATIONSHIPS; GEOGRAPHIC PARTHENOGENESIS; LEAF BEETLES; GENE FLOW; EVOLUTION; SELECTION; HYBRIDIZATION; ADAPTATION
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. DOI
12. Schwander, T; Crespi, BJ. (2009) Twigs on the tree of life? Neutral and selective models for integrating macroevolutionary patterns with microevolutionary processes in the analysis of asexuality.Molecular Ecology 18: 28-42 Twigs on the tree of life? Neutral and selective models for integrating macroevolutionary patterns with microevolutionary processes in the analysis of asexuality
NEW-ZEALAND SNAIL; MITOCHONDRIAL-DNA SEQUENCES; EVOLUTIONARY DEAD-END; GEOGRAPHICAL PARTHENOGENESIS; PHYLOGENETIC-RELATIONSHIPS; DELETERIOUS MUTATIONS; BDELLOID ROTIFERS; POTAMOPYRGUS-ANTIPODARUM; MOLECULAR PHYLOGENETICS; ENDOSYMBIOTIC BACTERIA
Neutral models characterize evolutionary or ecological patterns expected in the absence of specific causal processes, such as natural selection or ecological interactions. In this study, we describe and evaluate three neutral models that can, in principle, help to explain the apparent 'twigginess' of asexual lineages on phylogenetic trees without involving the negative consequences predicted for the absence of recombination and genetic exchange between individuals. Previously, such phylogenetic twiggyness of asexual lineages has been uncritically interpreted as evidence that asexuality is associated with elevated extinction rates and thus represents an evolutionary dead end. Our first model uses simple phylogenetic simulations to illustrate that, with sexual reproduction as the ancestral state, low transition rates to stable asexuality, or low rates of ascertained 'speciation' in asexuals, can generate twiggy distributions of asexuality, in the absence of high extinction rates for asexual lineages. The second model, developed by Janko et al. (2008), shows that a dynamic equilibrium between origins and neutral losses of asexuals can, under some conditions, generate a relatively low mean age of asexual lineages. The third model posits that the risk of extinction for asexual lineages may be higher than that of sexuals simply because asexuals inhabit higher latitudes or altitudes, and not due to effects of their reproductive systems. Such neutral models are useful in that they allow quantitative evaluation of whether empirical data, such as phylogenetic and phylogeographic patterns of sex and asexuality, indeed support the idea that asexually reproducing lineages persist over shorter evolutionary periods than sexual lineages, due to such processes as mutation accumulation, slower rates of adaptive evolution, or relatively lower levels of genetic variability. DOI
10.Crespi, B. (2008) Genomic imprinting in the development and evolution of psychotic spectrum conditions.Biological Reviews 83: 441-493 Genomic imprinting in the development and evolution of psychotic spectrum conditions
schizophrenia; psychosis; autism; genomic imprinting; evolution; genomic conflict PRADER-WILLI-SYNDROME; BIPOLAR AFFECTIVE-DISORDER; PARENT-OF-ORIGIN; MATERNAL UNIPARENTAL DISOMY; FAMILY-BASED ASSOCIATION; SMITH-MAGENIS-SYNDROME; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; LINKED MENTAL-RETARDATION; GENOMEWIDE LINKAGE SCAN; FACTOR BDNF GENE
I review and evaluate genetic and genomic evidence salient to the hypothesis that the development and evolution of psychotic spectrum conditions have been mediated in part by alterations of imprinted genes expressed in the brain. Evidence from the genetics and genomics of schizophrenia, bipolar disorder, major depression, Prader-Willi syndrome, Klinefelter syndrome, and other neurogenetic conditions support the hypothesis that the etiologies of psychotic spectrum conditions commonly involve genetic and epigenetic imbalances in the effects of imprinted genes, with a bias towards increased relative effects from imprinted genes with maternal expression or other genes favouring maternal interests. By contrast, autistic spectrum conditions, including Kanner autism, Asperger syndrome, Rett syndrome, Turner syndrome, Angelman syndrome, and Beckwith-Wiedemann syndrome, commonly engender increased relative effects from paternally expressed imprinted genes, or reduced effects from genes favouring maternal interests. Imprinted-gene effects on the etiologies of autistic and psychotic spectrum conditions parallel the diametric effects of imprinted genes in placental and foetal development, in that psychotic spectrum conditions tend to be associated with undergrowth and relatively-slow brain development, whereas some autistic spectrum conditions involve brain and body overgrowth, especially in foetal development and early childhood. An important role for imprinted genes in the etiologies of psychotic and autistic spectrum conditions is consistent with neurodevelopmental models of these disorders, and with predictions from the conflict theory of genomic imprinting. DOI
6.Crespi, B; Summers, K. (2005) Evolutionary biology of cancer.Trends in Ecology & Evolution 20: 545-552 Evolutionary biology of cancer
Cancer is driven by the somatic evolution of cell lineages that have escaped controls on replication and by the population-level evolution of genes that influence cancer risk. We describe here how recent evolutionary ecological studies have elucidated the roles of predation by the immune system and competition among normal and cancerous cells in the somatic evolution of cancer. Recent analyses of the evolution of cancer at the population level show how rapid changes in human environments have augmented cancer risk, how strong selection has frequently led to increased cancer risk as a byproduct, and how anticancer selection has led to tumor-suppression systems, tissue designs that slow somatic evolution, constraints on morphological evolution and even senescence itself. We discuss how applications of the tools of ecology and evolutionary biology are poised to revolutionize our understanding and treatment of this disease.
5.Crespi, BJ. (2004) Vicious circles: positive feedback in major evolutionary and ecological transitions.Trends in Ecology & Evolution 19: 627-633 Vicious circles: positive feedback in major evolutionary and ecological transitions
Evolutionary biologists and ecologists often focus on equilibrium states that are subject to forms of negative feedback, such as optima for phenotypic traits or regulation of population sizes. However, recent theoretical and empirical studies show how positive feedback can be instrumental in driving many of the most important and spectacular processes in evolutionary ecology, including the evolution of sex and genetic systems, mating systems, life histories, complex cooperation in insects and humans, ecological specialization, species diversity, species ranges, speciation and extinction. Taken together, this work suggests that positive feedback is more common than is generally appreciated, and that its self-reinforcing dynamics generate the conditions for changes that might otherwise be difficult or impossible for selection or other mechanisms to achieve. Testing for positive feedback requires analysing each causal link in feedback loops, tracking genetic, character and population-dynamic changes across generations, and elucidating the conditions that can result in self-reinforcing change.
4. Nosil, P; Crespi, BJ; Sandoval, CP. (2002) Host-plant adaptation drives the parallel evolution of reproductive isolation.Nature 417: 440-443 Host-plant adaptation drives the parallel evolution of reproductive isolation
Parallel evolution of similar traits in independent populations that inhabit ecologically similar environments strongly implicates natural selection as the cause of evolution(1). 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(1,2). 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(2-4). The parallel evolution of reproductive isolation provides strong evidence for natural selection in the process of speciation(1), but only one conclusive example from nature is known(2). 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(5,6). 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.
2.Crespi, BJ. (2001) The evolution of social behavior in microorganisms.Trends in Ecology & Evolution 16: 178-183 The evolution of social behavior in microorganisms
Recent studies of microorganisms have revealed diverse complex social behaviors, including cooperation in foraging, building, reproducing, dispersing and communicating. These microorganisms should provide novel,tractable systems for the analysis of social evolution. The application of evolutionary and ecological theory to understanding their behavior will aid in developing better means to control the many pathogenic bacteria that use social interactions to affect humans.
1. Carmean, D; Crespi, BJ. (1995) Do long branches attract flies?Nature 373: 666 Do long branches attract flies?
Strepsiptera and Diptera group together in phylogenetic analysis as an artefact resulting from the high substitution rates in their 18S rDNA sequences. The grouping is an excellent example of long-branch attraction resulting from the violation of the molecular clock for this gene. Website DOI
