Evolution of Thriftiness: An analytical viewpoint

We examine here, using a simple mathematical model, the conditions under which thrifty genes or fetal programming could evolve. Obesity and related disorders are thought to have their roots in metabolic thirftiness that evolved to combat periodic starvation. The failure to detect any thrifty genes and the association of low birth weight with type 2 diabetes, caused a shift in the concept from thrifty gene to thrifty phenotype and fetal programming. This hypothesis assumes that intra-uterine undernutrition programs the body to be thrifty, predicting and preparing for starvation in later life. However, there are reproductive costs associated with thriftiness. Results of the model suggest that under no condition thrifty and non-thrifty genes would co-exist stably in a population. The conditions for evolution of fetal programming are also very restricted. For species with longer life spans, programming for thriftiness is unlikely to evolve if starvation is decided by seasonality or stochastic annual climatic variations since the correlation between intra-uterine and life-time conditions is poor. On the other hand, if starvation is governed by longer periodicity factors such as population oscillations or social hierarchies, there can be better correlation between intra-uterine and life time conditions. Therefore social and population processes are more likely to have selected for fetal programming rather than seasonal and climatic “feast and famine” conditions. Since social and population processes can have cues other than diet, these cues may also influence the incidence of obesity related disorders as some recent evidence suggest

Hyperinsulinemia and insulin resistance : What comes first ?

Background

1)	Classical explanation :
Classical explanation of diabetic pathophysiology states that obesity induced insulin resistance develops first and is followed by compensatory hyperinsulinnemia. Further insulin resistance leads to prolonged, increased secretary demand on beta cells leading to subsequent secondary beta cell failure, giving rise to hyperglycaemia and diabetes^2^.

2)	 Neurobehavioral origin hypothesis :
The Neurobehavioral origin hypothesis suggests that insulin resistance mediates a shift from muscle dependent (soldier) to brain dependent (diplomat) strategies of making a livelihood. If nutrient limitation affects intrauterine development, brain development is the least affected among all the organs^4,5^. As a result, in IUGR babies muscle weight is poor but the brain is relatively well developed. Such a person is more likely to be a successful diplomat rather than a soldier and insulin resistance is adaptive for such an individual^3^. Since insulin is involved in brain development and cognitive functions, higher levels of insulin are needed. As insulin is having strong anti-lipolytic effect, hyperinsulinnemia is followed by subsequent excess fat accumulation. Also compensatory insulin resistance is needed to avoid hypoglycemia. This hypothesis predicts a reverse order of pathophysiology i.e. primary hyperinsulinnemia followed by compensatory insulin resistance^3^

Objective-
To determine in diabetes whether hyperinsulinnemia develops first or insulin resistance develops first.

Methods :
We searched literature for studies that investigated directly or indirectly the sequence of development of hyperinsulinnemia and insulin resistance in humans and animal models from an early stage. Meta-analysis was conducted on published data.

Results-
1)	In low birth weight neonates in humans as well as in rat models, hyperinsulinnemia is found at very early stage.^6^
2)	Development of insulin resistance is preceded by hyperinsulinnemia in mice, rats as well as in humans.^7, 8^
3)	In normoglycaemic hyperinsulinemia state if insulin production is suppressed insulin sensitivity increases rapidly maintaining the normoglycaemic state.^9,10^
4)	Beta cell expansion beginning in intrauterine life is independent of glucose, Insulin and Insulin receptors.^6^


Conclusion-
All the four lines of evidence indicate that hyperinsulinnemia precedes insulin resistance supporting the predictions of neurobehavioral origin hypothesis over the orthodox view.



References :
1)	DeFronzo RA, Ferrannini E (1991). Diabetes Care 14:173-194
2)	Kruszynska YT, Olefsky JM (1996). J Investig Med 44: 413-428.
3)	Watve MG, Yajnik CY (2007). BMC Evolutionary Biology.7: 61-74.
 4) Winick M, Rosso P, Waterlow JC (1970). Exp Neurol, 26:393-400.
 5) Winick M. (1969) J Pediatr,74:667-679.
 6) Chakravarthy MV et.al. (2008) Diabetes, 57:2698-2707.
 7) Ramin A et. al. (1998) J Clin Endo and Met, 83 :1911-1915.
 8) Hansen BC (1990) Am J Physiol Regul Integr Comp Physiol 259: 612-617.
 9) Stanley L (1981) Life Sciences, 28: 1829-1840.
 10) Ratzmann KP et. al. (1983) Int J Obes, 7 : 453-458

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Hypercytokinemia: Increased or decreased innate immunity?

The adipose tissue is an active endocrine organ which secretes proinflammatory cytokines and chemokines resulting into raised serum levels. Hypercytokinemia has been interpreted as raised level of innate immunity and its evolution is interpreted as a response to increased chances of infection under starvation conditions in which the thrifty phenotype evolved. If starvation and infection challenges co-occurred during hunter gatherer life, thrifty genotype and infection resistant genotype may have co-evolved. An inherent weakness of this explanation is that in obesity or insulin resistance there is no evidence of increased resistance to infections. The raised levels of inflammatory cytokines have not been demonstrated to combat infections or enhance wound healing. We suggest that the raised chemokine levels actually decrease peripheral innate immunity. The normal movement of monocyte-macrophages and neutrophils from blood vessels to injured tissue is under a chemokine gradient. A gradient results from the difference between the basal levels of chemokines and those secreted by the injured tissue. Increase in the basal level is expected to weaken the gradient thereby decreasing extravasation and infiltration. Using diffusion kinetics we show that a small rise in basal levels can cause substantial reduction in cell infiltration. This interpretation is consistent with the behavioural switch hypothesis proposed by Watve and Yajnik which suggests that obesity and insulin resistance mark a transition from “soldier” to “diplomat” lifestyle. Hypercytokinemia may have evolved as a mechanism of disinvestment in peripheral innate immunity since the diplomat lifestyle is less injury prone. We evaluate the two alternative hypotheses by available evidence

Caloric restriction causes symmetric cell division and delays aging in Escherichia coli

Aging is one of the most intriguing processes of biology and despite decades of research, many aspects of aging are poorly understood. Aging is known to occur in bacteria and yeast that divide with morphological asymmetry. Morphologically symmetrically dividing bacteria such as _Escherichia coli_ were assumed not to age until they were shown to divide with functional asymmetry leading to aging and death of some of the cells even in exponentially growing cultures. In asymmetrically dividing _E. coli_ the newly synthesized components are presumed to occupy one pole so that after division one of the daughter cells receives newly synthesized components whereas the other retains the older components. Mathematical models predicted that at the population level, asymmetric growth should result in higher growth rate and symmetric growth in higher growth yield. Therefore, arguably symmetric cell division should be selected in low nutrient environments and asymmetric division in nutrient rich environments. A further prediction was that lower substrate concentrations should strengthen repair mechanisms and suppress aging whereas higher substrate concentrations suppress repair and enhance aging. We show here that _E. coli_ divides more symmetrically under caloric restriction, that both genetic selection and phenotypic plasticity are important determinants of cell division symmetry and also that the proportion of cells that stop dividing and therefore are presumably dead is significantly lower in symmetrically dividing cultures. However, contrary to the prediction, symmetry was not always accompanied by reduced growth rate. These results demonstrate that asymmetry of division in _E. coli_ is not hardwired but responsive to the nutritional environment. This provides a new perspective on why caloric restriction increases lifespan in organisms ranging from microbes to mammals. Symmetry of division may be a mechanism spanning across the width of life forms but regulating aging in different ways in different forms

Ecological correlates of wildlife diseases

The parasite loads appear to differ widely within and between species of free ranging wild mammals. Using data on fecal propagule densities of 29 species of wild mammals from 20 wild life parks in India we tried to identify the ecological factors that are best predictors of parasite loads. Parasite loads were consistently negatively correlated with predatory pressures at both interspecific and intraspecific levels. Carnivores had higher mean parasite loads and the effect of diet and that of predatory pressure appeared to be independent of each other. No other ecological factors were significantly and consistently associated with fecal parasite loads

Evolution of Co-operation When the Strategies are Hidden: The Human Mating Game

Defection is frequently seen in co-operative systems [1-3]. Game theoretical solutions to stabilize cooperation rely on reciprocity and reputation in iterated games[4-5]. One of the basic requirements for reciprocity or reputation building is that the strategies of players and the resulting payoffs should be open at the end of every interaction. For games in which the strategies and payoffs remain hidden, these stabilizing factors are unlikely to work. We examine the evolution of cooperation for hidden-strategy games using human mating game as an example. Here faithful parenting can be considered as cooperation and extra-pair mating (EPM) or cuckoldry as defection. Cuckoldry may get exposed only occasionally and the genetic benefits of cuckoldry also remain hidden from the players. Along with mate guarding, social policing is enabled in humans by language and gossiping. However, social policing can be invaded by second order free riders. We suggest that opportunistic blackmailing, which is unique to hidden strategy games can act as a keystone strategy in stabilizing co-operation. This can counteract free riding and stabilize policing. A game theoretical model results into a rock - paper – scissor (R-P-S) like situation with no evolutionary stable strategy (ESS). Simulations result into a stable or stably oscillating polymorphism. Obligate monogamy is an essential trait in the co-existence. In a gender difference model too, polymorphism is seen in both genders but with different traits predominating in the two genders. The model explains intra-gender, inter-gender as well as cross cultural variability in mating strategies in humans

Refinement of defection strategies stabilizes cooperation

Cooperation among unrelated individuals is an enduring evolutionary riddle and a number of possible solutions have been suggested. Most of these suggestions attempt to refine cooperative strategies, while little attention is given to the fact that novel defection strategies can also evolve in the population. Especially in the presence of punishment to the defectors and public knowledge of strategies employed by the players, a defecting strategy that avoids getting punished by selectively cooperating only with the punishers can get a selective benefit over non-conditional defectors. Furthermore, if punishment ensures cooperation from such discriminating defectors, defectors who punish other defectors can evolve as well. We show that such discriminating and punishing defectors can evolve in the population by natural selection in a Prisoner's Dilemma game scenario, even if discrimination is a costly act. These refined defection strategies destabilize unconditional defectors. They themselves are, however, unstable in the population. Discriminating defectors give selective benefit to the punishers in the presence of non-punishers by cooperating with them and defecting with others. However, since these players also defect with other discriminators they suffer fitness loss in the pure population. Among the punishers, punishing cooperators always benefit in contrast to the punishing defectors, as the latter not only defect with other punishing defectors but also punish them and get punished. As a consequence of both these scenarios, punishing cooperators get stabilized in the population. We thus show ironically that refined defection strategies stabilize cooperation. Furthermore, cooperation stabilized by such defectors can work under a wide range of initial conditions and is robust to mistakes

Group selection and reciprocity among Kin

The question how Darwinian mechanisms lead to the evolution of individually costly cooperative behavior has given rise to a number of hypotheses. However, attempts to build a synthesis where different types of mechanisms coexist and interact at different levels of selections are still scarce. Here we derive simple game theoretical models where the group level conflicts are resolved by group selection while simultaneously within group competition is resolved by kin selection and reciprocity. We show that none of the mechanisms, when alone, is as robust in evolving and maintaining cooperation as a synthesis of all. Furthermore, we show that initially within group conflicts can be overcome only by kin selection and not reciprocity. However, once common, different types of reciprocities can maintain high levels of cooperation even if average relatedness among individuals is lowered, groups become large, and the benefits of cooperation are reduced. Based on the synthesis we also propose a possible route to the evolution of social and eusocial systems

_Streptomyces_ sp. as predators of bacteria

Background: The ecological role of actinomycetes and their secondary metabolites is not yet completely understood. 
Hypothesis: Actinomycetes and Streptomyces sp. in particular, are non-obligate predators of bacteria in soil. 
Evidence: Ability to grow on live bacterial cells as a sole source of nutrients. Prey cell lysis accompanying growth. Circumstantial evidence for the involvement of antimicrobials along with enzymes.
Implications: This finding may open up a new source of novel secondary metabolites from the genus

Money handling influences BMI: a survey of cashiers

Money is a recent phenomenon in the evolutionary history of man and therefore no separate brain centre to handle money is likely to have evolved. The brain areas activated by food reward and money reward are extensively overlapping. In an experimental set-up, hunger was demonstrated to influence money related decisions and money related thoughts to influence hunger. This suggests that the brain areas evolved for handling food related emotions are exapted to handle money and therefore there could be a neuronal cross-talk between food and money. If this is true then attitude and behavior related to money and wealth could influence obesity. We conducted a survey of 211 individuals working as full time cashiers in order to test whether ownership over the cash, the amount of cash handled per day and the duration of cash handling work affected their body mass index (BMI). Cashiers who had ownership over the money had a significantly higher age corrected mean BMI than salaried cashiers. The BMI correlated positively with duration of service as cashier even after correcting for age and duration of sedentary job in males. Among salaried cashiers of both sexes, bank cashiers whose mean daily cash handling was one or two orders of magnitude greater than that of shop cashiers, had a significantly higher BMI. The effects of amount of money handled per day, years of service as cashier and ownership over the money handled could be shown to influence BMI independent of each other. The results support the exaptation hypothesis and suggest that the changing economy and attitudes towards money may be a contributing factor to the current obesity epidemic