A simple model of unbounded evolutionary versatility as a largest-scale trend in organismal evolution

The idea that there are any large-scale trends in the evolution of biological organisms is highly controversial. It is commonly believed, for example, that there is a large-scale trend in evolution towards increasing complexity, but empirical and theoretical arguments undermine this belief. Natural selection results in organisms that are well adapted to their local environments, but it is not clear how local adaptation can produce a global trend. In this paper, I present a simple computational model, in which local adaptation to a randomly changing environment results in a global trend towards increasing evolutionary versatility. In this model, for evolutionary versatility to increase without bound, the environment must be highly dynamic. The model also shows that unbounded evolutionary versatility implies an accelerating evolutionary pace. I believe that unbounded increase in evolutionary versatility is a large-scale trend in evolution. I discuss some of the testable predictions about organismal evolution that are suggested by the model

Avalanche dynamics in Bak-Sneppen evolution model observed with standard distribution width of fitness

We introduce the standard distribution width of fitness to characterize the global and individual features of a ecosystem in the Bak-Sneppen evolution model. Through tracking this quantity in evolution, a different hierarchy of avalanche dynamics, $w_{0}$ avalanche is observed. The corresponding gap equation and the self-organized threshold $w_{c}$ are obtained. The critical exponents $\tau ,$ $\gamma$and $\rho$, which describe the behavior of the avalanche size distribution, the average avalanche size and the relaxation to attractor, respectively, are calculated with numerical simulation. The exact master equation and $\gamma$ equation are derived. And the scaling relations are established among the critical exponents of this new avalanche.Comment: 14 pages, 3 figure

A forward genetic screen identifies host factors that influence the lysis-lysogeny decision in phage lambda

The lysis‐lysogeny decision made by bacteriophage lambda is one of the classic problems of molecular biology. Shortly after infecting a cell, the virus can either go down the lytic pathway and make more viruses, or go down the lysogenic pathway and integrate itself into the host genome. While much is known about how this decision takes place, the extent to which host physiology influences this decision and the mechanisms by which this influence takes place has remained mysterious. To answer this question, we performed a forward genetic screen to systematically identify all of the genes in E. coli that influence the lysis‐lysogeny decision. Our results demonstrate previously unknown links between host physiology and viral decision making and shed new light on this classic system

Evolutionary instability of Zero Determinant strategies demonstrates that winning isn't everything

Zero Determinant (ZD) strategies are a new class of probabilistic and conditional strategies that are able to unilaterally set the expected payoff of an opponent in iterated plays of the Prisoner's Dilemma irrespective of the opponent's strategy, or else to set the ratio between a ZD player's and their opponent's expected payoff. Here we show that while ZD strategies are weakly dominant, they are not evolutionarily stable and will instead evolve into less coercive strategies. We show that ZD strategies with an informational advantage over other players that allows them to recognize other ZD strategies can be evolutionarily stable (and able to exploit other players). However, such an advantage is bound to be short-lived as opposing strategies evolve to counteract the recognition.Comment: 14 pages, 4 figures. Change in title (again!) to comply with Nature Communications requirements. To appear in Nature Communication

The diplomat's dilemma: Maximal power for minimal effort in social networks

Closeness is a global measure of centrality in networks, and a proxy for how influential actors are in social networks. In most network models, and many empirical networks, closeness is strongly correlated with degree. However, in social networks there is a cost of maintaining social ties. This leads to a situation (that can occur in the professional social networks of executives, lobbyists, diplomats and so on) where agents have the conflicting objectives of aiming for centrality while simultaneously keeping the degree low. We investigate this situation in an adaptive network-evolution model where agents optimize their positions in the network following individual strategies, and using only local information. The strategies are also optimized, based on the success of the agent and its neighbors. We measure and describe the time evolution of the network and the agents' strategies.Comment: Submitted to Adaptive Networks: Theory, Models and Applications, to be published from Springe

The developmental dynamics of terrorist organizations

We identify robust statistical patterns in the frequency and severity of violent attacks by terrorist organizations as they grow and age. Using group-level static and dynamic analyses of terrorist events worldwide from 1968-2008 and a simulation model of organizational dynamics, we show that the production of violent events tends to accelerate with increasing size and experience. This coupling of frequency, experience and size arises from a fundamental positive feedback loop in which attacks lead to growth which leads to increased production of new attacks. In contrast, event severity is independent of both size and experience. Thus larger, more experienced organizations are more deadly because they attack more frequently, not because their attacks are more deadly, and large events are equally likely to come from large and small organizations. These results hold across political ideologies and time, suggesting that the frequency and severity of terrorism may be constrained by fundamental processes.Comment: 28 pages, 8 figures, 4 tables, supplementary materia

A forward genetic screen identifies host factors that influence the lysis-lysogeny decision in phage lambda

The lysis‐lysogeny decision made by bacteriophage lambda is one of the classic problems of molecular biology. Shortly after infecting a cell, the virus can either go down the lytic pathway and make more viruses, or go down the lysogenic pathway and integrate itself into the host genome. While much is known about how this decision takes place, the extent to which host physiology influences this decision and the mechanisms by which this influence takes place has remained mysterious. To answer this question, we performed a forward genetic screen to systematically identify all of the genes in E. coli that influence the lysis‐lysogeny decision. Our results demonstrate previously unknown links between host physiology and viral decision making and shed new light on this classic system

Proliferation Index: A Continuous Model to Predict Prognosis in Patients with Tumours of the Ewing's Sarcoma Family

The prognostic value of proliferation index (PI) and apoptotic index (AI), caspase-8, -9 and -10 expression have been investigated in primary Ewing's sarcoma family of tumours (ESFT). Proliferating cells, detected by immunohistochemistry for Ki-67, were identified in 91% (91/100) of tumours with a median PI of 14 (range 0–87). Apoptotic cells, identified using the TUNEL assay, were detected in 96% (76/79) of ESFT; the median AI was 3 (range 0–33). Caspase-8 protein expression was negative (0) in 14% (11/79), low (1) in 33% (26/79), medium (2) in 38% (30/79) and high (3) in 15% (12/79) of tumours, caspase-9 expression was low (1) in 66% (39/59) and high (3) in 34% (20/59), and caspase-10 protein was low (1) in 37% (23/62) and negative (0) in 63% (39/62) of primary ESFT. There was no apparent relationship between caspase-8, -9 and -10 expression, PI and AI. PI was predictive of relapse-free survival (RFS; p = 0.011) and overall survival (OS; p = <0.001) in a continuous model, whereas AI did not predict outcome. Patients with tumours expressing low levels of caspase-9 protein had a trend towards a worse RFS than patients with tumours expressing higher levels of caspase-9 protein (p = 0.054, log rank test), although expression of caspases-8, -9 and/or -10 did not significantly predict RFS or OS. In a multivariate analysis model that included tumour site, tumour volume, the presence of metastatic disease at diagnosis, PI and AI, PI independently predicts OS (p = 0.003). Consistent with previous publications, patients with pelvic tumours had a significantly worse OS than patients with tumours at other sites (p = 0.028); patients with a pelvic tumour and a PI≥20 had a 6 fold-increased risk of death. These studies advocate the evaluation of PI in a risk model of outcome for patients with ESFT

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations

Redirecting T Cells to Ewing's Sarcoma Family of Tumors by a Chimeric NKG2D Receptor Expressed by Lentiviral Transduction or mRNA Transfection

We explored the possibility to target Ewing's sarcoma family of tumors (ESFT) by redirecting T cells. To this aim, we considered NKG2D-ligands (NKG2D-Ls) as possible target antigens. Detailed analysis of the expression of MICA, MICB, ULBP-1, -2, and -3 in fourteen ESFT cell lines revealed consistent expression of at least one NKG2D-L. Thus, for redirecting T cells, we fused a CD3ζ/CD28-derived signaling domain to the ectodomain of NKG2D, however, opposite transmembrane orientation of this signaling domain and NKG2D required inverse orientation fusion of either of them. We hypothesized that the particularly located C-terminus of the NKG2D ectodomain should allow reengineering of the membrane anchoring from a native N-terminal to an artificial C-terminal linkage. Indeed, the resulting chimeric NKG2D receptor (chNKG2D) was functional and efficiently mediated ESFT cell death triggered by activated T cells. Notably, ESFT cells with even low NKG2D-L expression were killed by CD8pos and also CD4pos cells. Both, mRNA transfection and lentiviral transduction resulted in high level surface expression of chNKG2D. However, upon target-cell recognition receptor surface levels were maintained by tranfected RNA only during the first couple of hours after transfection. Later, target-cell contact resulted in strong and irreversible receptor down-modulation, whereas lentivirally mediated expression of chNKG2D remained constant under these conditions. Together, our study defines NKG2D-Ls as targets for a CAR-mediated T cell based immunotherapy of ESFT. A comparison of two different methods of gene transfer reveals strong differences in the susceptibility to ligand-induced receptor down-modulation with possible implications for the applicability of RNA transfection