Domestication and microbiome succession may drive pathogen spillover.

Emerging infectious diseases have posed growing medical, social and economic threats to humanity. The biological background of pathogen spillover or host switch, however, still has to be clarified. Disease ecology finds pathogen spillovers frequently but struggles to explain at the molecular level. Contrarily, molecular biological traits of host-pathogen relationships with specific molecular binding mechanisms predict few spillovers. Here we aim to provide a synthetic explanation by arguing that domestication, horizontal gene transfer even between superkingdoms as well as gradual exchange of microbiome (microbiome succession) are essential in the whole scenario. We present a new perspective at the molecular level which can explain the observations of frequent pathogen spillover events at the ecological level. This proposed rationale is described in detail, along with supporting evidence from the peer-reviewed literature and suggestions for testing hypothesis validity. We also highlight the importance of systematic monitoring of virulence genes across taxonomical categories and in the whole biosphere as it helps prevent future epidemics and pandemics. We conclude that that the processes of domestication, horizontal gene transfer and microbial succession might be important mechanisms behind the many spillover events driven and accelerated by climate change, biodiversity loss and globalization.

Tick bite induced α-gal syndrome highlights anticancer effect of allergy.

Tick bite induced α-gal syndrome (AGS) following consumption of mammalian meat is a recently described intriguing disease occurring worldwide. Here we argue that AGS and delayed allergy in general is an adaptive defence method against cancer. Our hypothesis synthesizes two lines of supporting evidence. First, allergy has been shown to have direct anti-cancer effects with unknown mechanism. Second, eating processed meat was shown to be linked to developing cancer. Humans lost their genes encoding molecules α-gal 30 MYA and Neu5Gc 2 MYA, the latter co-occurring with the start of using fire. These molecules are acquired from external sources, as tick bite for α-gal and mammalian meat for Neu5Gc, the latter accumulating in tumors. The resulting specific delayed allergic response is a molecular adaptation to fight cancer. By further testing and applying our hypothesis, new avenues in cancer research and therapy will open that might save lives and decrease human suffering.

Harm or protection? The adaptive function of tick toxins.

The existence of tick toxins is an old enigma that has intrigued scientists for a long time. The adaptive value of using deadly toxins for predatory animals is obvious: they try to kill the prey in the most effective way or protect themselves from their natural enemies. Ticks, however, are blood-sucking parasites, and it seems paradoxical that they have toxins similar to spiders, scorpions and snakes. Based on published data, here we examine the potential adaptive function of different types of toxins produced by soft and hard ticks. We hypothesize that there are diverse evolutionary roles behind (a) to attack and reduce the tick-transmitted pathogens inside the vertebrate host systemically to protect the tick, (b) to paralyse the host to stop grooming, (c) to speed up host heartbeat to improve blood supply and (d) to inhibit the process of necroptosis to prevent the rejection of hard ticks. We will provide published evidence that supports the above-mentioned hypotheses, and we will give an outlook how these new scientific results might be applied in modern pharmacology and medicine.

Paradoxes of tumour complexity: somatic selection, vulnerability by design, or infectious aetiology?

The aetiology of cancer involves intricate cellular and molecular mechanisms that apparently emerge on the short timescale of a single lifetime. Some of these traits are remarkable not only for their complexity, but also because it is hard to conceive selection pressures that would favour their evolution within the local competitive microenvironment of the tumour. Examples include 'niche construction' (re-programming of tumour-specific target sites) to create permissive conditions for distant metastases; long-range feedback loops of tumour growth; and remarkably 'plastic' phenotypes (e.g. density-dependent dispersal) associated with metastatic cancer. These traits, which we term 'paradoxical tumour traits', facilitate the long-range spread or long-term persistence of the tumours, but offer no apparent benefit, and might even incur costs in the competition of clones within the tumour. We discuss three possible scenarios for the origin of these characters: somatic selection driven by specific selection regimes; non-adaptive emergence due to inherent vulnerabilities in the organism; and manipulation by putative transmissible agents that contribute to and benefit from these traits. Our work highlights a lack of understanding of some aspects of tumour development, and offers alternative hypotheses that might guide further research.

The evolutionary logic of sepsis.

The recently proposed Microbiome Mutiny Hypothesis posits that members of the human microbiome obtain information about the host individuals' health status and, when host survival is compromised, switch to an intensive exploitation strategy to maximize residual transmission. In animals and humans, sepsis is an acute systemic reaction to microbes invading the normally sterile body compartments. When induced by formerly mutualistic or neutral microbes, possibly in response to declining host health, sepsis appears to fit the 'microbiome mutiny' scenario except for its apparent failure to enhance transmission of the causative organisms. We propose that the ability of certain species of the microbiome to induce sepsis is not a fortuitous side effect of within-host replication, but rather it might, in some cases, be the result of their adaptive evolution. Whenever host health declines, inducing sepsis can be adaptive for those members of the healthy human microbiome that are capable of colonizing the future cadaver and spread by cadaver-borne transmission. We hypothesize that such microbes might exhibit switches along the 'mutualist - lethal pathogen - decomposer - mutualist again' scenario, implicating a previously unsuspected, surprising level of phenotypic plasticity. This hypothesis predicts that those species of the healthy microbiome that are recurring causative agents of sepsis can participate in the decomposition of cadavers, and can be transmitted as soil-borne or water-borne infections. Furthermore, in individual sepsis cases, the same microbial clones that dominate the systemic infection that precipitates sepsis, should also be present in high concentration during decomposition following death: this prediction is testable by molecular fingerprinting in experimentally induced animal models. Sepsis is a leading cause of human death worldwide. If further research confirms that some cases of sepsis indeed involve the 'mutiny' (facultative phenotypic switching) of normal members of the microbiome, then new strategies could be devised to prevent or treat sepsis by interfering with this process.

The microbiome mutiny hypothesis: can our microbiome turn against us when we are old or seriously ill?

BACKGROUND: The symbiotic organisms of the healthy microbiome tend to be harmless or even beneficial for the host; however, some symbionts are able to adjust their virulence in response to external stimuli. Evolutionary theory suggests that optimal virulence might increase if the mortality of the host (from unrelated causes) increases. PRESENTATION OF THE HYPOTHESIS: We hypothesize that microorganisms of the human microbiome may be capable of a coordinated phenotypic switch to higher virulence ("microbiome mutiny") in old or seriously ill people, to optimize their transmission under the conditions of increased background mortality. This proposed virulence shift might contribute to the death of old or seriously ill people even in the absence of apparent disease. TESTING THE HYPOTHESIS: Testable predictions of the hypothesis include increased expression of virulence factors in isolates of the same species of the microbiome obtained from ailing/old versus healthy/young individuals, and the existence of microbial mechanisms to assess the general condition (background mortality) of the host. Such tests are going to be important to distinguish the cases of "microbiome mutiny" from the situation where opportunistic infections or increased effective virulence arise from relaxed immune control in ailing or old individuals in the absence of changes in the symbionts/pathogens. IMPLICATIONS OF THE HYPOTHESIS: Elucidating this potential mechanism might open up new possibilities for the clinical management of age related health issues and critical injuries or disease. Targeted prophylaxis against the microbes capable of virulence shifts could break the harmful feedback loop between deteriorating health and the "mutiny" of the microbiome.

Why infest the loved ones--inherent human behaviour indicates former mutualism with head lice.

Head lice transmit to new hosts when people lean their heads together. Humans frequently touch their heads to express friendship or love, while this behaviour is absent in apes. We hypothesize that this behaviour was adaptive because it enabled people to acquire head lice infestations as early as possible to provoke an immune response effective against both head lice and body lice throughout the subsequent periods of their life. This cross-immunity could provide some defence against the body-louse-borne lethal diseases like epidemic typhus, trench fever, relapsing fever and the classical plague. Thus the human 'touching heads' behaviour probably acts as an inherent and unconscious 'vaccination' against body lice to reduce the threat exposed by the pathogens they may transmit. Recently, the eradication of body-louse-borne diseases rendered the transmission of head lice a maladaptive, though still widespread, behaviour in developed societies.

Sociosexually unrestricted parents have more sons: a further application of the generalized Trivers-Willard hypothesis (gTWH).

BACKGROUND: The generalized Trivers-Willard hypothesis (gTWH) proposes that parents who possess any heritable trait which increases male reproductive success at a greater rate than female reproductive success in a given environment will have a higher-than-expected offspring sex ratio, and parents who possess any heritable trait which increases the female reproductive success at a greater rate than male reproductive success in a given environment will have a lower-than-expected offspring sex ratio. AIM: One heritable trait which increases the reproductive success of sons much more than that of daughters is unrestricted sociosexual orientation. We therefore predict that parents with unrestricted sociosexual orientation (measured by the number of sexual partners, frequency of sex, and attitudes toward relationship commitment and sexual exclusivity) have a higher-than-expected offspring sex ratio (more sons). SUBJECTS AND METHOD: We analyse the US General Social Surveys and the National Longitudinal Study of Adolescent Health (Add Health), both with large nationally representative samples. RESULTS: Our analyses support the prediction from the gTWH. CONCLUSION: One standard deviation increase in unrestrictedness of sociosexual orientation increases the odds of having a son by 12-19% in the representative American samples.

The tripartite immune conflict in placentals and a hypothesis on fetal-->maternal microchimerism.

There is a two-way traffic of immune cells through the placenta; and fetal immune cells are often present in the maternal body even long after giving birth. We present an adaptationist theory to interpret fetal-->maternal microchimerism and the diverse set of concomitant medical phenomena. We handle fetal, maternal, and paternal adaptive interests separately and in interaction with one another. Fetuses may benefit from immunological information gathered by migrant cells in the maternal body, and also from improved maternal defence. However, they may be jeopardized by a selfish maternal usage of fetal-->maternal microchimerism - i.e., some mothers get pregnant only to improve their immune system and then to abort. The use of microchimeric cells by the maternal immune system may contribute to the adaptive benefits of female choosiness and polyandry. While fathers may enjoy an indirect benefit from enhanced fetal and maternal health, they also face the risk of wasting sexual efforts due to selfish pregnancies of cheating females. Paternal alleles acting via clones of microchimeric cells in the maternal body could launch an immunological attack against the non-kin sperm in the female genitalia, or against the non-kin fetus in the womb. Furthermore, an intraspecific version of Zahavi's Mafia Hypothesis could explain a potential interaction between the abortion of fetuses and a subsequent rise of an autoimmune disease. We suggest that males may be capable to provoke microchimerism-induced autoimmune-like diseases in the mother in revenge of selfish pregnancies. This hypothetic paternal threat could increase the maternal costs associated to selfish pregnancies. From a medical point of view, we propose new interpretations for autoimmune-like diseases, infertility, miscarriage, and also for the prevailing connections among them. Specifically, we argue that miscarriages may cause autoimmune diseases, a reversed causality as compared to the currently accepted one.

Deal in the womb: fetal opiates, parent-offspring conflict, and the future of midwifery.

This paper argues that parent-offspring conflict is mediated by placental beta-endorphins in placental mammals, i.e., foetuses make their mothers endorphin-dependent then manipulate them to increase nutrient allocation to the placenta. This hypothesis predicts that: (1) anatomic position of endorphin production should mirror its presumed role in fetal-maternal conflict; (2) endorphin levels should co-vary positively with nutrient carrying capacity of maternal blood system; (3) postpartum psychological symptoms (postpartum blues, depression and psychosis) in humans are side-effects of this mechanism that can be interpreted as endorphin-deprivation symptoms; (4) shortly after parturition, placentophagia could play an adaptive role in decreasing the negative side-effects of fetal manipulation; (5) later, breast-feeding induced endorphin excretion of the maternal pituitary saves mother from further deprivation symptoms. Finally, whatever the molecular mechanism of fetal manipulation is, widespread and intense medical care (such as caesarean section and use of antidepressants) affects the present and future evolution of mother-foetus conflict in the human species (and also in domestic animals) to increase 'fetal aggressiveness' and thus technology-dependency of reproduction.