Showing papers in "Evolution, Medicine, and Public Health in 2020"

Lifetime cancer prevalence and life history traits in mammals

Abstract: Author(s): Boddy, Amy M; Abegglen, Lisa M; Pessier, Allan P; Aktipis, Athena; Schiffman, Joshua D; Maley, Carlo C; Witte, Carmel | Abstract: Background:Cancer is a common diagnosis in many mammalian species, yet they vary in their vulnerability to cancer. The factors driving this variation are unknown, but life history theory offers potential explanations to why cancer defense mechanisms are not equal across species. Methodology:Here we report the prevalence of neoplasia and malignancy in 37 mammalian species, representing 11 mammalian orders, using 42 years of well curated necropsy data from the San Diego Zoo and San Diego Zoo Safari Park. We collected data on life history components of these species and tested for associations between life history traits and both neoplasia and malignancy, while controlling for phylogenetic history. Results:These results support Peto's paradox, in that we find no association between lifespan and/or body mass and the prevalence of neoplasia or malignancy. However, a positive relationship exists between litter size and prevalence of malignancy (P = 0.005, Adj. R2 = 0.212), suggesting that a species' life history strategy may influence cancer vulnerabilities. Lastly, we tested for the relationship between placental invasiveness and malignancy. We find no evidence for an association between placental depth and malignancy prevalence (P = 0.618, Adj. R2 = 0.068). Conclusions:Life history theory offers a powerful framework to understand variation in cancer defenses across the tree of life. These findings provide insight into the relationship between life history traits and cancer vulnerabilities, which suggest a trade-off between reproduction and cancer defenses. Lay summary:Why are some mammals more vulnerable to cancer than others? We test whether life history trade-offs may explain this variation in cancer risk. Bigger, longer-lived animals do not develop more cancer compared to smaller, shorter-lived animals. However, we find a positive association between litter size and cancer prevalence in mammals.

Phage steering of antibiotic-resistance evolution in the bacterial pathogen, Pseudomonas aeruginosa.

Abstract: Background and objectives Antimicrobial resistance is a growing global concern and has spurred increasing efforts to find alternative therapeutics. Bacteriophage therapy has seen near constant use in Eastern Europe since its discovery over a century ago. One promising approach is to use phages that not only reduce bacterial pathogen loads but also select for phage resistance mechanisms that trade-off with antibiotic resistance-so called 'phage steering'. Methodology Recent work has shown that the phage OMKO1 can interact with efflux pumps and in so doing select for both phage resistance and antibiotic sensitivity of the pathogenic bacterium Pseudomonas aeruginosa. We tested the robustness of this approach to three different antibiotics in vitro (tetracycline, erythromycin and ciprofloxacin) and one in vivo (erythromycin). Results We show that in vitro OMKO1 can reduce antibiotic resistance of P. aeruginosa (Washington PAO1) even in the presence of antibiotics, an effect still detectable after ca.70 bacterial generations in continuous culture with phage. Our in vivo experiment showed that phage both increased the survival times of wax moth larvae (Galleria mellonella) and increased bacterial sensitivity to erythromycin. This increased antibiotic sensitivity occurred both in lines with and without the antibiotic. Conclusions and implications Our study supports a trade-off between antibiotic resistance and phage sensitivity. This trade-off was maintained over co-evolutionary time scales even under combined phage and antibiotic pressure. Similarly, OMKO1 maintained this trade-off in vivo, again under dual phage/antibiotic pressure. Our findings have implications for the future clinical use of steering in phage therapies. Lay Summary: Given the rise of antibiotic-resistant bacterial infection, new approaches to treatment are urgently needed. Bacteriophages (phages) are bacterial viruses. The use of such viruses to treat infections has been in near-continuous use in several countries since the early 1900s. Recent developments have shown that these viruses are not only effective against routine infections but can also target antibiotic resistant bacteria in a novel, unexpected way. Similar to other lytic phages, these so-called 'steering phages' kill the majority of bacteria directly. However, steering phages also leave behind bacterial variants that resist the phages, but are now sensitive to antibiotics. Treatment combinations of these phages and antibiotics can now be used to greater effect than either one independently. We evaluated the impact of steering using phage OMKO1 and a panel of three antibiotics on Pseudomonas aeruginosa, an important pathogen in hospital settings and in people with cystic fibrosis. Our findings indicate that OMKO1, either alone or in combination with antibiotics, maintains antibiotic sensitivity both in vitro and in vivo, giving hope that phage steering will be an effective treatment option against antibiotic-resistant bacteria.

How evolutionary behavioural sciences can help us understand behaviour in a pandemic

Abstract: The COVID-19 pandemic has brought science into the public eye and to the attention of governments more than ever before. Much of this attention is on work in epidemiology, virology and public health, with most behavioural advice in public health focusing squarely on 'proximate' determinants of behaviour. While epidemiological models are powerful tools to predict the spread of disease when human behaviour is stable, most do not incorporate behavioural change. The evolutionary basis of our preferences and the cultural evolutionary dynamics of our beliefs drive behavioural change, so understanding these evolutionary processes can help inform individual and government decision-making in the face of a pandemic. Lay summary: The COVID-19 pandemic has brought behavioural sciences into the public eye: Without vaccinations, stopping the spread of the virus must rely on behaviour change by limiting contact between people. On the face of it, "stop seeing people" sounds simple. In practice, this is hard. Here we outline how an evolutionary perspective on behaviour change can provide additional insights. Evolutionary theory postulates that our psychology and behaviour did not evolve to maximize our health or that of others. Instead, individuals are expected to act to maximise their inclusive fitness (i.e, spreading our genes) - which can lead to a conflict between behaviours that are in the best interests for the individual, and behaviours that stop the spread of the virus. By examining the ultimate explanations of behaviour related to pandemic-management (such as behavioural compliance and social distancing), we conclude that "good of the group" arguments and "one size fits all" policies are unlikely to encourage behaviour change over the long-term. Sustained behaviour change to keep pandemics at bay is much more likely to emerge from environmental change, so governments and policy makers may need to facilitate significant social change - such as improving life experiences for disadvantaged groups.

Lions, Tigers and Kittens too: ACE2 and susceptibility to CoVID-19

Abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has been reported to infect domesticated animals in a species-specific manner, where cats were susceptible but not dogs. Using the recently published crystal structure of the SARS-CoV-2 spike protein complexed with the human host cell receptor angiotensin converting enzyme 2 (ACE2), we characterized the structure and evolution of ACE2 in several of these species and identify a single interacting amino acid residue conserved between human and Felidae ACE2 but not in Canidae that correlates with virus susceptibility. Using computational analyses we describe how this site likely affects ACE2 targeting by the virus. Thus, we highlight how evolution-based approaches can be used to form hypotheses and study animal transmission of such viruses in the future.

The Maternal Nutritional Buffering Model: an evolutionary framework for pregnancy nutritional intervention

Abstract: Evidence that fetal nutrition influences adult health has heightened interest in nutritional interventions targeting pregnancy. However, as is true for other placental mammals, human females have evolved mechanisms that help buffer the fetus against short-term fluctuations in maternal diet and energy status. In this review, we first discuss the evolution of increasingly elaborate vertebrate strategies of buffering offspring from environmental fluctuations during development, including the important innovation of the eutherian placenta. We then present the Maternal Nutritional Buffering Model, which argues that, in contrast to many micronutrients that must be derived from dietary sources, the effects of short-term changes in maternal macronutrient intake during pregnancy, whether due to a deficit or supplementation, will be minimized by internal buffering mechanisms that work to ensure a stable supply of essential resources. In contrast to the minimal effects of brief macronutrient supplementation, there is growing evidence that sustained improvements in early life and adult pre-pregnancy nutrition could improve birth outcomes in offspring. Building on these and other observations, we propose that strategies to improve fetal macronutrient delivery will be most effective if they modify the pregnancy metabolism of mothers by targeting nutrition prior to conception and even during early development, as a complement to the conventional focus on bolstering macronutrient intake during pregnancy itself. Our model leads to the prediction that birth weight will be more strongly influenced by the mother's chronic pre-pregnancy nutrition than by pregnancy diet, and highlights the need for policy solutions aimed at optimizing future, intergenerational health outcomes. Lay summary: We propose that strategies to improve fetal macronutrient delivery will be most effective if they modify the pregnancy metabolism of mothers by targeting nutrition prior to conception and even during early development, as a complement to the conventional focus on bolstering macronutrient intake during pregnancy itself.

An African origin for Mycobacterium bovis.

Abstract: Background and objectives Mycobacterium bovis and Mycobacterium caprae are two of the most important agents of tuberculosis in livestock and the most important causes of zoonotic tuberculosis in humans. However, little is known about the global population structure, phylogeography and evolutionary history of these pathogens. Methodology We compiled a global collection of 3364 whole-genome sequences from M.bovis and M.caprae originating from 35 countries and inferred their phylogenetic relationships, geographic origins and age. Results Our results resolved the phylogenetic relationship among the four previously defined clonal complexes of M.bovis, and another eight newly described here. Our phylogeographic analysis showed that M.bovis likely originated in East Africa. While some groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world. Conclusions and implications Our results allow a better understanding of the global population structure of M.bovis and its evolutionary history. This knowledge can be used to define better molecular markers for epidemiological investigations of M.bovis in settings where whole-genome sequencing cannot easily be implemented. Lay summary During the last few years, analyses of large globally representative collections of whole-genome sequences (WGS) from the human-adapted Mycobacterium tuberculosis complex (MTBC) lineages have enhanced our understanding of the global population structure, phylogeography and evolutionary history of these pathogens. In contrast, little corresponding data exists for M. bovis, the most important agent of tuberculosis in livestock. Using whole-genome sequences of globally distributed M. bovis isolates, we inferred the genetic relationships among different M. bovis genotypes distributed around the world. The most likely origin of M. bovis is East Africa according to our inferences. While some M. bovis groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world driven by cattle movements.

Old friends meet a new foe: A potential role for immune-priming parasites in mitigating COVID-19 morbidity and mortality.

Abstract: The novel virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the associated Coronavirus Disease 2019 (COVID-19) represent a pathogen to which human beings have limited to no evolved immune response. The most severe symptoms are associated with overactive inflammatory immune responses, leading to a cytokine storm, tissue damage, and death, if not balanced and controlled. Hypotheses within Evolutionary Medicine, including the Hygiene/Old Friends Hypothesis, provide an important lens through which to understand and possibly control this overactive immune response. In this article, we explore the role that infection with soil-transmitted helminths (STHs; i.e. intestinal parasitic worms) may play in dampening SARS-CoV-2 symptoms and mitigating the worst COVID-19 outcomes. Specifically, STHs stimulate the immunosuppressive and regulatory T-helper 2 (TH2) branch of the immune system, which decreases ACE2-receptor expression (i.e. receptors SARS-CoV-2 uses to infect host cells), balances the inflammatory TH1/TH17 branches of the immune system triggered by SARS-CoV-2 infection, and reduces inflammation through the release of anti-inflammatory/regulatory cytokines. Because STHs are common and affect the most vulnerable and marginalized members of society, it is especially important to consider how these parasites may impact COVID-19 outcomes. Areas experiencing endemic STH infections are often characterized by a lack of preventative infrastructure and medical care, which may further exacerbate risk of SARS-CoV-2 infection and COVID-19 development. For this reason, we also explore biocultural factors that contribute to disease outcomes for both SARS-CoV-2 and STH infections. Biocultural and Evolutionary Medicine perspectives on COVID-19 are crucial for understanding the global impact of the disease. Lay summary: An evolutionary perspective is required to understand the global impact and various presentations of COVID-19. We consider how coinfection with soil-transmitted helminths (common parasitic worms that coevolved with humans) may suppress inflammatory immune activity, thereby potentially reducing COVID-19 disease severity. Structural and lifestyle factors shaping coinfection patterns are also discussed.

Knowledge and practices regarding antibiotics use: Findings from a cross-sectional survey among Italian adults.

Abstract: Background and objectives This study aimed to assess the knowledge on antibiotics and antimicrobial resistance (AMR) and the antibiotic use among the general public in Southern Italy and to analyze whether sociodemographic characteristics could be associated with poor knowledge and improper practices. Methodology From March to November 2019, a face-to-face interview was conducted with adult subjects attending the waiting room of 27 randomly selected general practitioners (GPs) in Southern Italy. The questionnaire covered sociodemographic characteristics, knowledge on antibiotics and AMR and practices regarding the consumption of and self-medication with antibiotics. Results The response rate was 89.7%. In the sample, 29.2% thought that antibiotics are effective for viral infections, and 49.5% correctly recognized the definition of AMR. Predictors of good knowledge about antibiotics and AMR were female gender and a higher education level. Almost half of the respondents had used antibiotics in the previous year and 23.6% took antibiotics to treat a common cold and/or fever. Among participants, 25.5% reported to have bought antibiotics without a prescription, and 30.6% were classified as antibiotic self-medication users. Use of antibiotics in the previous 12 months and having taken an antibiotic after a phone consultation with the GP were positively associated with both antibiotic use for a common cold and/or fever and self-medication with antibiotics. Conclusions and implications The findings of this study highlighted a considerable antibiotic consumption in the adult population of Southern Italy together with misconceptions regarding the correct indication for antibiotic use that could foster indiscriminate antibiotic use. Lay summary The findings of this study highlighted a considerable antibiotic consumption in the adult Italian population together with misconceptions regarding the correct indication for antibiotic use that could foster indiscriminate antibiotic use. Almost a quarter of the respondents took antibiotics to treat a common cold and/or fever and reported to have bought antibiotics without a prescription.

Evidence for height and immune function trade-offs among preadolescents in a high pathogen population.

Abstract: Author(s): Garcia, Angela R; Blackwell, Aaron D; Trumble, Benjamin C; Stieglitz, Jonathan; Kaplan, Hillard; Gurven, Michael D | Abstract: BackgroundIn an energy-limited environment, caloric investments in one characteristic should trade-off with investments in other characteristics. In high pathogen ecologies, biasing energy allocation towards immune function over growth would be predicted, given strong selective pressures against early-life mortality.MethodologyIn the present study, we use flow cytometry to examine trade-offs between adaptive immune function (T cell subsets, B cells), innate immune function (natural killer cells), adaptive to innate ratio and height-for-age z scores (HAZ) among young children (N = 344; aged 2 months-8 years) in the Bolivian Amazon, using maternal BMI and child weight-for-height z scores (WHZ) as proxies for energetic status.ResultsMarkers of adaptive immune function negatively associate with child HAZ, a pattern most significant in preadolescents (3+ years). In children under three, maternal BMI appears to buffer immune and HAZ associations, while child energetic status (WHZ) moderates relationships in an unexpected direction: HAZ and immune associations are greater in preadolescents with higher WHZ. Children with low WHZ maintain similar levels of adaptive immune function, but are shorter compared to high WHZ peers.ConclusionsReduced investment in growth in favor of immunity may be necessary for survival in high pathogen contexts, even under energetic constraints. Further, genetic and environmental factors are important considerations for understanding variation in height within this population. These findings prompt consideration of whether there may be a threshold of investment into adaptive immunity required for survival in high pathogen environments, and thus question the universal relevance of height as a marker of health.Lay summaryAdaptive immune function is negatively associated with child height in this high pathogen environment. Further, low weight-for-height children are shorter but maintain similar immune levels. Findings question the relevance of height as a universal health marker, given that costs and benefits of height versus immunity may be calibrated to local ecology.

Randolph M. Nesse, Good Reasons for Bad Feelings: Insights from the Frontier of Evolutionary Psychiatry

Abstract: The modern world, it seems, needs all the psychiatric help it can muster. In Europe, 38% of the population suffers from at least one mental disorder annually [1]. This is similar to the 35% of global college students who report having a mental disorder [2]. In America, 4 70 000 people died from drug overdoses in 2017 [3]—the latest year for which reliable statistics are available—and nearly 50 000 more died from suicide [4]. These numbers do not include an estimated 88 000 deaths from alcohol abuse or nearly 500 000 more attributed to cigarette smoking. Against all evolutionary logic, we seem to be working hard to do ourselves in. Against this backdrop of disturbing news, I picked up Randy Nesse’s engaging new book, Good Reasons for Bad Feelings: Insights from the Frontier of Evolutionary Psychiatry (Dutton, $28.00), in the hope that it would help me understand a bit more about the human behavior and especially mental states, disorders, and diseases than I currently did. I was not disappointed. Nesse, of course, is one of the founders of the field of evolutionary medicine. His 1991 Quarterly Review of Biology paper with George Williams brought together many of the ideas that still drive the field. Surprisingly, although I have read many of his papers since then, and heard him give more than a few talks, I had never before come to know Nesse’s outlook on his own chosen discipline, psychiatry. The book is gracefully written for an educated lay audience in four parts. Part 1 (Why Are Mental Disorders So Confusing?) lays out the basics of an evolutionary thinking about mental disorders and also traces Nesse’s own gradual awakening to what an evolutionary perspective could add to his understanding of his own patients, even though it might not necessarily suggest new therapies. Nesse is a traditionally trained, and before he encountered evolutionary thinking, a traditionally trained practicing psychiatrist. Consequently, one thing this book is not is an attack on traditional psychiatry. Given his long history of listening carefully to his patients, Nesse is aware that traditional, talking and drug-treatment based, psychiatric treatment is often helpful and necessary. What an evolutionary perspective has to offer is to bring some order to a chaos of symptoms and overlapping diagnoses as well as insight into the origins of moods, emotions and psychiatric diseases. The main messages I took from this part of the book are first that psychiatry too often fails to distinguish symptoms from diseases. This can lead to ignoring the importance of the situations that arouse extremes of emotion, such as anxiety and depression that psychiatrists deal with on a daily basis. Second, Nesse emphasizes a core feature of evolutionary medicine, namely that there are good evolutionary reasons, such as the mismatch between the modern environment and the environment in which we evolved, that natural selection has left us vulnerable to certain diseases, including mental diseases. Third, he points out a core problem for psychiatric diagnosis is the lack of a coherent perspective on the normal useful functions of moods and emotions. His book, in fact, provides such a perspective. The second part of the book (Reasons for Feelings) elaborates on this third point. Even if you are not a particularly introspective person—and I am not— this part of the book will make you freshly evaluate your own moods and emotions. Nesse’s hypothesis is that even seemingly negative emotions such as anxiety, depression, anger and guilt exist because they are part of a naturally selected system of adaptive responses to specific situations and that absence of such responses can be harmful. Painful emotions, for instance, can motivate us to change, escape, or avoid certain situations. These are the good reasons for bad feelings—his book’s title. Invoking what he calls the Smoke Detector book review 28

Evolutionary perspectives on human behavior during the coronavirus pandemic: Insights from game theory.

Abstract: The coronavirus pandemic constitutes a global challenge to society and medicine. Here, we review evolutionary insights that are relevant for the understanding of how people respond to the pandemic and what to expect in the aftermath of the crisis. Specifically, we argue that the behavioral immune system (BIS) and sickness behavior (SB) comprise two adaptive responses to impending and actual infection, respectively, and that individuals activating their BIS differ from those showing SB in important ways that may have implications for the prevention and treatment of COVID-19. Moreover, we reframe some of the behavioral health issues associated with the pandemic in a game-theoretical scenario, illustrating the difficulties that arise when public health is treated as a 'public good'. Lay summary: The coronavirus pandemic constitutes a global challenge to society and medicine. In this article, we employ evolutionary theory to improve our understanding of how people respond to the pandemic. Specifically, we argue that human behavior is guided by ancient mechanisms involving either the avoidance of infection or defense against attacks in times of enhanced vulnerability. Moreover, we reframe some of the behavioral health issues associated with the pandemic in a game-theoretical scenario. This helps understand why most people comply with rules of social distancing, while a minority fails to do so for very different reasons. The evolutionary perspective also allows making some predictions for the course of the pandemic.

Culture, behavior and health.

Abstract: Department of Anthropology, Pennsylvania State University, University Park, State College, PA 16802, USA and Department of Anthropology, University of Toronto, Toronto, Ontario, Canada *Corresponding author. Department of Anthropology, Pennsylvania State University, 516 Carpenter Building, University Park, State College, PA 16802, USA. Tel: (814) 865-2509; Fax: (814) 863-1474. E-mail: mzh235@psu.edu

Immune function during pregnancy varies between ecologically distinct populations.

Abstract: Background and objectives Among placental mammals, females undergo immunological shifts during pregnancy to accommodate the fetus (i.e. fetal tolerance). Fetal tolerance has primarily been characterized within post-industrial populations experiencing evolutionarily novel conditions (e.g. reduced pathogen exposure), which may shape maternal response to fetal antigens. This study investigates how ecological conditions affect maternal immune status during pregnancy by comparing the direction and magnitude of immunological changes associated with each trimester among the Tsimane (a subsistence population subjected to high pathogen load) and women in the USA. Methodology Data from the Tsimane Health and Life History Project (N = 935) and the National Health and Nutrition Examination Survey (N = 1395) were used to estimate population-specific effects of trimester on differential leukocyte count and C-reactive protein (CRP), a marker of systemic inflammation. Results In both populations, pregnancy was associated with increased neutrophil prevalence, reduced lymphocyte and eosinophil count and elevated CRP. Compared to their US counterparts, pregnant Tsimane women exhibited elevated lymphocyte and eosinophil counts, fewer neutrophils and monocytes and lower CRP. Total leukocyte count remained high and unchanged among pregnant Tsimane women while pregnant US women exhibited substantially elevated counts, resulting in overlapping leukocyte prevalence among all third-trimester individuals. Conclusions and implications Our findings indicate that ecological conditions shape non-pregnant immune baselines and the magnitude of immunological shifts during pregnancy via developmental constraints and current trade-offs. Future research should investigate how such flexibility impacts maternal health and disease susceptibility, particularly the degree to which chronic pathogen exposure might dampen inflammatory response to fetal antigens. Lay summary This study compares immunological changes associated with pregnancy between the Tsimane (an Amazonian subsistence population) and individuals in the USA. Results suggest that while pregnancy enhances non-specific defenses and dampens both antigen-specific immunity and parasite/allergy response, ecological conditions strongly influence immune baselines and the magnitude of shifts during gestation.

Evolutionary medical insights into the SARS-CoV-2 pandemic

Abstract: The author apply concepts and tools from evolutionary medicine to understanding the SARS-CoV-2 pandemic. The pandemic represents a mismatched conflict, with dynamics and pathology apparently driven by three main factors: (i) bat immune systems that rely on low inflammation but high efficacy of interferon-based defenses; (ii) viral tactics that differentially target the human interferon system, leading to substantial asymptomatic and pre-symptomatic transmission; and (ii) high mortality caused by hyper-inflammatory and hyper-coagulatory phenotypes, that represent dysregulated tradeoffs whereby collateral immune-induced damage becomes systemic and severe. This framework can explain the association of mortality with age (which involves immune life-history shifts towards higher inflammation and coagulation and reduced adaptive immunity), and sex (since males senesce faster than females). Genetic-risk factors for COVID-19 mortality can be shown, from a phenome-wide association analysis of the relevant SNPs, to be associated with inflammation and coagulation; the phenome-wide association study also provides evidence, consistent with several previous studies, that the calcium channel blocking drug amlodipine mediates risk of mortality. Lay Summary: SARS-CoV-2 is a bat virus that jumped into humans. The virus is adapted to bat immune systems, where it evolved to suppress the immune defenses (interferons) that mammals use to tell that they are infected. In humans, the virus can apparently spread effectively in the body with a delay in the production of symptoms and the initiation of immune responses. This delay may then promote overactive immune responses, when the virus is detected, that damage the body as a side effect. Older people are more vulnerable to the virus because they are less adapted to novel infectious agents, and invest less in immune defense, compared to younger people. Genes that increase risk of mortality from SARS-CoV-2 are functionally associated with a drug called amlodipine, which may represent a useful treatment.

Conservation analysis of SARS-CoV-2 spike suggests complicated viral adaptation history from bat to human

Abstract: Background The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-CoV-2, has become the most devastating public health emergency in the 21st century and one of the most influential plagues in history. Studies on the origin of SARS-CoV-2 have generally agreed that the virus probably comes from bat, closely related to a bat CoV named BCoV-RaTG13 taken from horseshoe bat (Rhinolophus affinis), with Malayan pangolin (Manis javanica) being a plausible intermediate host. However, due to the relatively low number of SARS-CoV-2-related strains available in public domain, the evolutionary history remains unclear. Methodology Nine hundred ninety-five coronavirus sequences from NCBI Genbank and GISAID were obtained and multiple sequence alignment was carried out to categorize SARS-CoV-2 related groups. Spike sequences were analyzed using similarity analysis and conservation analyses. Mutation analysis was used to identify variations within receptor-binding domain (RBD) in spike for SARS-CoV-2-related strains. Results We identified a family of SARS-CoV-2-related strains, including the closest relatives, bat CoV RaTG13 and pangolin CoV strains. Sequence similarity analysis and conservation analysis on spike sequence identified that N-terminal domain, RBD and S2 subunit display different degrees of conservation with several coronavirus strains. Mutation analysis on contact sites in SARS-CoV-2 RBD reveals that human-susceptibility probably emerges in pangolin. Conclusion and implication We conclude that the spike sequence of SARS-CoV-2 is the result of multiple recombination events during its transmission from bat to human, and we propose a framework of evolutionary history that resolve the relationship of BCoV-RaTG13 and pangolin coronaviruses with SARS-CoV-2. Lay summary This study analyses whole-genome and spike sequences of coronavirus from NCBI using phylogenetic and conservation analyses to reconstruct the evolutionary history of severe acute respiratory syndrome (SARS)-CoV-2 and proposes an evolutionary history of spike in the progenitors of SARS-CoV-2 from bat to human through mammal hosts before they recombine into the current form.

The impact of early life antibiotic use on atopic and metabolic disorders: Meta-analyses of recent insights.

Abstract: Background and objectives The impact of antibiotics use early in life on later-in-life morbidities has received substantial attention as explanations for atopic and metabolic disorders with a surge as modern lifestyle diseases. The objective of this study was to perform meta-analyses to determine if antibiotics administration during the first 2 years of infant life is associated with increased risks of atopic or metabolic disorders later in life. Methodology We screened more than 100 English-language prospective and retrospective studies published between January 2002 and March 2020 and assessed study quality using the Newcastle-Ottawa scale. We performed overall and subgroup meta-analyses on 31 high-quality comparable studies on atopic and 23 on metabolic disorders, involving more than 3.5 million children. Results Antibiotic exposure prenatally and during the first 2 years of life significantly impacts the risk of developing atopic and metabolic disorders. Exposure during the first 6 months of life appears most critical, consistent with this being the time when the microbiome is most susceptible to irreversible perturbations. The presence of dose-response associations and stronger impacts of broad- than narrow-spectrum antibiotics further point to effects being mediated by microbiota-induced changes. Conclusions and implications Our findings support that antibiotics use is a mismatch to modernity that can negatively affect the symbiotic associations we rely on for proper immune function and metabolism. Improving our understanding of these associations, the underlying proximate mechanisms and the impact of antibiotics use on future human-symbiont evolution will be important to improve human health. Lay summary The use of antibiotics in infancy has been suggested to increase the risks of atopic and metabolic disorders later in life. Through meta-analyses of more than 100 studies of >3.5 million children, we confirm these risks, and show that patterns are consistent with effects being due to microbiota-driven changes.

Comments on Boddy et al. 2020: Available data suggest positive relationship between placental invasion and malignancy.

Abstract: Yale Systems Biology Institute, West Haven, CT 06516, USA; Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06520, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Medical School, New Haven, CT 06510, USA; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48202, USA; Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA and Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA *Corresponding author. Yale Systems Biology Institute, West Haven, CT 06516, USA. E-mail: gunter.wagner@yale.edu Received 1 June 2020; revised version accepted 2 July 2020

Links between metabolic syndrome and the microbiome.

Abstract: Metabolic syndrome (MetS) is a cluster of harmful conditions which occur together, such as insulin resistance, abdominal obesity, and hypertension. The global prevalence of MetS is growing rapidly, with some estimates suggesting over one billion people worldwide experience increased morality and disease rates linked with this syndrome. One possible factor contributing to MetS risk is changes in microbiome composition. Approximately 100 trillion bacteria and other microbes reside in the human intestinal tract, collectively termed the gut microbiome. Humans and microbes share a long evolutionary history, with many of these microbes influencing human health outcomes. However, environmental conditions have changed dramatically with human technological innovations; many of these changes (e.g., diets high in processed foods and sedentary lifestyles) appear to impact human-microbe relationships. In general, recent changes in diet and activity patterns have been linked to decreased microbiome diversity, elevating inflammation and metabolic disease risk and likely promoting the development of MetS. Targeting patient diet or exercise patterns may therefore help doctors better treat patients suffering from MetS. Still, additional work is needed to determine how the microbiome responds to changes in patient activity and diet patterns across culturally and biologically diverse human populations.

Anthropocene-related disease: The inevitable outcome of progressive niche modification?

Abstract: While the Anthropocene is often discussed in terms of the health of the planet, there has been less attention paid to its impact on the health of humans. We argue that there is now sufficient evidence of broad and growing adverse effects on human health to consider Anthropocene-related diseases and their impact on public health as a category of conditions needing specific recognition and preventative action. Using the examples of climate change-related health challenges, non-communicable disease, antimicrobial resistance and the unique challenges of the digital environment, we discuss how the profound and pervasive environmental changes of the Anthropocene can affect our health, with broad effects on societal health. We frame this concept in terms of human evolutionary history and cultural evolution's runaway characteristics, reflecting our drive for continual and cumulative innovation for reasons beyond simply survival and Darwinian fitness. As the causative agents are often remote from those populations most adversely affected, prevention and mitigation require collective societal and policy actions. Lay summary: There is increasing evidence that our uniquely evolved ability to modify our environments rapidly and at an accelerating pace is having impacts on our health, particularly non-communicable diseases and poor mental wellbeing. Reframing these public health challenges as Anthropocene-related diseases emphasizes the need for collective responsibility and systems approaches to prevention.

Evolutionary consequences of feedbacks between within-host competition and disease control.

Abstract: Lay Summary: Competition often occurs among diverse parasites within a single host, but control efforts could change its strength. We examined how the interplay between competition and control could shape the evolution of parasite traits like drug resistance and disease severity.

Treatment timing shifts the benefits of short and long antibiotic treatment over infection.

Abstract: Antibiotics are the major tool for treating bacterial infections. Rising antibiotic resistance, however, calls for a better use of antibiotics. While classical recommendations favor long and aggressive treatments, more recent clinical trials advocate for moderate regimens. In this debate, two axes of 'aggression' have typically been conflated: treatment intensity (dose) and treatment duration. The third dimension of treatment timing along each individual's infection course has rarely been addressed. By using a generic mathematical model of bacterial infection controlled by immune response, we examine how the relative effectiveness of antibiotic treatment varies with its timing, duration and antibiotic kill rate. We show that short or long treatments may both be beneficial depending on treatment onset, the target criterion for success and on antibiotic efficacy. This results from the dynamic trade-off between immune response build-up and resistance risk in acute, self-limiting infections, and uncertainty relating symptoms to infection variables. We show that in our model early optimal treatments tend to be 'short and strong', while late optimal treatments tend to be 'mild and long'. This suggests a shift in the aggression axis depending on the timing of treatment. We find that any specific optimal treatment schedule may perform more poorly if evaluated by other criteria, or under different host-specific conditions. Our results suggest that major advances in antibiotic stewardship must come from a deeper empirical understanding of bacterial infection processes in individual hosts. To guide rational therapy, mathematical models need to be constrained by data, including a better quantification of personal disease trajectory in humans. Lay summary: Bacterial infections are becoming more difficult to treat worldwide because bacteria are becoming resistant to the antibiotics used. Addressing this problem requires a better understanding of how treatment along with other host factors impact antibiotic resistance. Until recently, most theoretical research has focused on the importance of antibiotic dosing on antibiotic resistance, however, duration and timing of treatment remain less explored. Here, we use a mathematical model of a generic bacterial infection to study three aspects of treatment: treatment dose/efficacy (defined by the antibiotic kill rate), duration, and timing, and their impact on several infection endpoints. We show that short and long treatment success strongly depends on when treatment begins (defined by the symptom threshold), the target criterion to optimize, and on antibiotic efficacy. We find that if administered early in an infection, "strong and short" therapy performs better, while if treatment begins at higher bacterial densities, a "mild and long" course of antibiotics is favored. In the model host immune defenses are key in preventing relapses, controlling antibiotic resistant bacteria and increasing the effectiveness of moderate intervention. In order to improve rational treatments of human infections, we call for a better quantification of individual disease trajectories in bacteria-immunity space.

A test of oscillation in the human secondary sex ratio.

Abstract: Author(s): Catalano, Ralph; Casey, Joan A; Bruckner, Tim A | Abstract: Background and objectivesThe sex ratio of human birth cohorts predicts the health and longevity of their members. Most literature invokes natural selection in support of the argument that heritable tendencies to produce male or female offspring induce oscillation in the sex ratio and its sequelae. Tests of the argument remain exceedingly rare because they require vital statistics describing many generations of a population both unaffected by migration and exposed to an exogenous stressor virulent enough to change the sex ratio at birth. We contribute to the literature by using time-series modeling to detect oscillation in the best data currently available for such a test.MethodologyWe apply rigorous time-series methods to data describing Sweden from 1751 through 1830, a period when the population not only aged in place without migration, but also exhibited the effects of an Icelandic volcanic eruption including a historically low secondary sex ratio. That very low sex ratio should have induced oscillation if heritable mechanisms appear in humans.ResultsWe detected oscillation in the ratio but not that predicted by heritable tendencies to produce males or females. We found peak-to-trough oscillation at 14 rather than the approximately 32 years expected from the heritable tendencies argument.Conclusions and implicationsOur findings suggest that mechanisms other than perturbation of heritable tendencies to produce males or females induce oscillation in the human secondary sex ratio. These other mechanisms may include reproductive suppression and selection in utero.Lay summaryThe male to female ratio in human birth cohorts predicts longevity but its variation over time remains unexplained. We test the long-held theory that the ratio oscillates due to heritable tendencies to produce males or females. We find oscillation, but it appears due to social processes rather than heritable mechanisms.

Effect of drug dose and timing of treatment on the emergence of drug resistance in vivo in a malaria model.

Abstract: Background and objectives There is a significant interest in identifying clinically effective drug treatment regimens that minimize the de novo evolution of antimicrobial resistance in pathogen populations. However, in vivo studies that vary treatment regimens and directly measure drug resistance evolution are rare. Here, we experimentally investigate the role of drug dose and treatment timing on resistance evolution in an animal model. Methodology In a series of experiments, we measured the emergence of atovaquone-resistant mutants of Plasmodium chabaudi in laboratory mice, as a function of dose or timing of treatment (day post-infection) with the antimalarial drug atovaquone. Results The likelihood of high-level resistance emergence increased with atovaquone dose. When varying the timing of treatment, treating either very early or late in infection reduced the risk of resistance. When we varied starting inoculum, resistance was more likely at intermediate inoculum sizes, which correlated with the largest population sizes at time of treatment. Conclusions and implications (i) Higher doses do not always minimize resistance emergence and can promote the emergence of high-level resistance. (ii) Altering treatment timing affects the risk of resistance emergence, likely due to the size of the population at the time of treatment, although we did not test the effect of immunity whose influence may have been important in the case of late treatment. (iii) Finding the 'right' dose and 'right' time to maximize clinical gains and limit resistance emergence can vary depending on biological context and was non-trivial even in our simplified experiments. Lay summary In a mouse model of malaria, higher drug doses led to increases in drug resistance. The timing of drug treatment also impacted resistance emergence, likely due to the size of the population at the time of treatment.

Why is preventing antibiotic resistance so hard? Analysis of failed resistance management.

Abstract: We describe the case of a patient with pancreatitis followed by intra-abdominal infection in which source control was not achieved Antimicrobial therapy led to the emergence of resistance in multiple organisms through multiple population dynamics processes While the initial insult was not due to infection, subsequent infections with resistant organisms contributed to a poor outcome for the patient Though resistance evolution was a known risk, it was difficult to predict the next organism that would arise in the setting of antibiotic pressure and its resistance profile This case illustrates the clinical challenge of antibiotic resistance that current approaches cannot readily prevent LAY SUMMARY Why is antibiotic resistance management so complex? Distinct evolutionary processes unfold when antibiotic treatment is initiated that lead, separately and together, to the undesired outcome of antibiotic resistance This clinical case exemplifies some of those processes and highlights the dire need for evolutionary risk assessments to be incorporated into clinical decision making

Spondylolysis and spinal adaptations for bipedalism: The overshoot hypothesis.

Abstract: Background and objectives The study reported here focused on the aetiology of spondylolysis, a vertebral pathology usually caused by a fatigue fracture. The goal was to test the Overshoot Hypothesis, which proposes that people develop spondylolysis because their vertebral shape is at the highly derived end of the range of variation within Homo sapiens. Methodology We recorded 3D data on the final lumbar vertebrae of H. sapiens and three great ape species, and performed three analyses. First, we compared H. sapiens vertebrae with and without spondylolysis. Second, we compared H. sapiens vertebrae with and without spondylolysis to great ape vertebrae. Lastly, we compared H. sapiens vertebrae with and without spondylolysis to great ape vertebrae and to vertebrae of H. sapiens with Schmorl’s nodes, which previous studies have shown tend to be located at the ancestral end of the range of H. sapiens shape variation. Results We found that H. sapiens vertebrae with spondylolysis are significantly different in shape from healthy H. sapiens vertebrae. We also found that H. sapiens vertebrae with spondylolysis are more distant from great ape vertebrae than are healthy H. sapiens vertebrae. Lastly, we found that H. sapiens vertebrae with spondylolysis are at the opposite end of the range of shape variation than vertebrae with Schmorl’s nodes. Conclusions Our findings indicate that H. sapiens vertebrae with spondylolysis tend to exhibit highly derived traits and therefore support the Overshoot Hypothesis. Spondylolysis, it appears, is linked to our lineage’s evolutionary history, especially its shift from quadrupedalism to bipedalism. Lay summary: Spondylolysis is a relatively common vertebral pathology usually caused by a fatigue fracture. There is reason to think that it might be connected with our lineage’s evolutionary shift from walking on all fours to walking on two legs. We tested this idea by comparing human vertebrae with and without spondylolysis to the vertebrae of great apes. Our results support the hypothesis. They suggest that people who experience spondylolysis have vertebrae with what are effectively exaggerated adaptations for bipedalism.

Fish consumption is associated with school performance in children in a non-linear way: Results from the German cohort study KiGGS.

Abstract: How the long chain fatty acids DHA and EPA in the diet permitted human brain evolution, and how much our brains need today to function optimally are still hot topics for debate. DHA and EPA are considered as semi-essential because only insufficient amounts can be produced from other nutrients, such that they must be ingested with the diet. However, the Dietary Reference Intake (DRI) of DHA and EPA, or of fish containing these fatty acids, has not yet been established. Eating fish is often recommended and generally considered beneficial for health and cognitive development in children and adolescents. For this study, data from a large cohort study were analysed to assess the association between fish consumption and cognitive school performance in children and adolescents. Methods Data from the German cohort of children and adolescent health KiGGS, which was conducted 2003-2006 and included more than 17’000 children, were analysed. Ordered logistic regressions were performed to test for associations between fish intake and school performance. Potential confounders were included in the models. Results A statistically significant association was found between an intake of 8 g of fish per day and the probability of increasing the final grade in German (OR 1.193, 95% CI 1.049-1.358) and mathematics (OR 1.16, 95% CI 1.022-1.317) by one point, compared to no or very limited fish consumption. For the outcome German, higher levels of fish intake also showed a positive effect. These relationships were not linear, but tended to decrease again at higher doses of fish. Discussion Our result confirms previous reports of a positive association between fish intake and school performance. Interestingly, this relationship was not linear, but tended to decrease again in the highest categories of fish intake. We hypothesize that mercury or other pollutants in the fish could be detrimental at high levels. As only half of all children met the minimal fish intake recommendations, fish consumption should be promoted more strongly in children in order to meet the minimal requirements of long-chain polyunsaturated fatty acids (LC-PUFAs).

Adoption of outgroup norms provides evidence for social transmission in perinatal care practices among rural Namibian women.

Abstract: Background and objectives How do new ideas spread in social groups? We apply the framework of cultural evolution theory to examine what drives change in perinatal care norms among Himba women in the Kunene region of Namibia. Access to formal medical care is on the rise in this region, and medical workers regularly visit communities to promote WHO-recommended perinatal care practices. This study investigates how various forms of social transmission affect women's uptake of medical recommendations concerning perinatal care. Methodology Based on interviews with one hundred Himba mothers, we used Bayesian multi-level logistical regression models to examine how perceptions of group preferences, prestige ascribed to outgroup conformers, interaction with the outgroup and access to resources affect norm adoption. Results Women who perceive medical recommendations as common in their group prefer, plan and practice these recommendations more often themselves. We observed a shift toward medical recommendations regarding birth location and contraception use that was in line with conformity bias predictions. Practices that serve as cultural identity markers persist in the population. Conclusions and implications Norm changes, and the cultural evolutionary processes that can lead to them, are not uniform, either in process or pace. Empirical studies like this one provide important examples of how these changes reflect local culture and circumstance and are critical for better understanding the models that currently predominate in cultural evolution work. These cases can also help bridge the gap between evolutionary anthropology and public health by demonstrating where promotion and prevention campaigns might be most effective. Lay Summary The recent promotion of WHO-recommended perinatal care practices in Namibia provides an opportunity to empirically study norm change using a cultural evolution framework. We found women adopt medical recommendations when they believe these are common in their social group. Local norms that were not discouraged persisted in the study group.

Brown adipose tissue and type 2 diabetes.

Abstract: Recent work proposes that a regimen of repeated mild cold exposure may have protective effects against the development of type II diabetes mellitus (T2D) by activating brown adipose tissue (BAT) metabolism. BAT may protect against by increasing whole-body energy expenditure and insulin sensitivity. An evolutionary perspective, however, highlights several limitations of this hypothesis. Some individuals adapt to acute cold stress by constricting their blood vessels, which leads to high blood pressure. Thus, a regimen of repeated mild cooling may have beneficial health effects for some individuals and negative consequences for others. Future research should examine the relationships between low temperature exposure, BAT metabolism, blood pressure, and type II diabetes risk.

COVID-19 and evolutionary medicine.

Abstract: Crises like the current pandemic allow us to see clearly our evolutionary legacy in terms of behaviour. Human innate conduct becomes obvious in crisis situations. It ranges from excessive altruism to extreme selfishness. Despite the rational underpinnings of governmental recommendations, people often do not follow minimal hygiene or social distancing. Human panic reactions are unconscious and irrational. They were formed by our earlier living conditions where flight-or-fight behaviours had adaptive value. Official rules often are not effective because of natural resistance towards orders that are counter-intuitive and constrain personal freedoms. We are not adapted to alter our routines quickly. This is why attempts at preventing the spread of infections will typically slow down transmission but are often unable to eliminate the pathogen. Humans are not evolutionarily programmed for sustainable behaviour reaching beyond a short time horizon. Thus, planning reserves in the medical care and political system are counter-intuitive and, in conjunction with constant pressures on institutional economies, fails in crisis situations. People tend to forget and neglect catastrophes that occurred too far back in time. For example, in Switzerland, there is a concept of a Katastrophenlücke (‘disaster gap’, a term first used by C. Pfister, University of Berne, in relation to the lack of major natural disasters for more than 100 years). Old catastrophic situations tend to repeat themselves after generational memory fades.