Divergence, demography and gene loss along the human lineage

Genomic DNA sequences are an irreplaceable source for reconstructing the vanished past of living organisms. Based on updated sequence data, this paper summarizes our studies on species divergence time, ancient population size and functional loss of genes in the primate lineage leading to modern humans (Homo sapiens sapiens). The inter- and intraspecific comparisons of DNA sequences suggest that the human lineage experienced a rather severe bottleneck in the Middle Pleistocene, throughout which period the subdivided African population played a predominant role in shaping the genetic architecture of modern humans. Also, published and newly identified human-specific pseudogenes (HSPs) are enumerated in order to infer their significance for human evolution. Of the 121 candidate genes obtained, authentic HSPs turn out to comprise only 25 olfactory receptor genes, four T cell receptor genes and nine other genes. The fixation of HSPs has been too rare over the past 6–7 Myr to account for species differences between humans and chimpanzees

Molecular Clock on a Neutral Network

The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating the topological structure of a neutral network from empirical measurements of the substitution process.Comment: 10 page

Implantable Sensor System for Remote Detection of a Restenosis Condition

Part 7: Perceptional SystemsInternational audienceThe increase of life expectancy in the European Union, and the high risk of cardiovascular diseases associated with age, are some of the main factors to contribute to the rise of healthcare costs. An intelligent stent (e-stent), capable of obtaining and transmitting real-time measurements of physiological parameters for its clinical consultation, can be a useful tool for long-term monitoring, diagnostic, and early warning system for arterial blockage without patient hospitalization. In this paper, a behavioural model of capacitive Micro-Electro-Mechanical (MEMS) pressure sensor is proposed and simulated under several restenosis conditions. Special attention has been given to the need of an accurate fault model, obtained from realistic finite-element simulations,to ensure long-term reliability; particularly for those faults whose behavior cannot be easily described by an analytical model

Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages Under Selection

SELECTOR is a software package for studying the evolution of multiallelic genes under balancing or positive selection while simulating complex evolutionary scenarios that integrate demographic growth and migration in a spatially explicit population framework. Parameters can be varied both in space and time to account for geographical, environmental, and cultural heterogeneity. SELECTOR can be used within an approximate Bayesian computation estimation framework. We first describe the principles of SELECTOR and validate the algorithms by comparing its outputs for simple models with theoretical expectations. Then, we show how it can be used to investigate genetic differentiation of loci under balancing selection in interconnected demes with spatially heterogeneous gene flow. We identify situations in which balancing selection reduces genetic differentiation between population groups compared with neutrality and explain conflicting outcomes observed for human leukocyte antigen loci. These results and three previously published applications demonstrate that SELECTOR is efficient and robust for building insight into human settlement history and evolution

Statistics of selectively neutral genetic variation

Random models of evolution are instrumental in extracting rates of microscopic evolutionary mechanisms from empirical observations on genetic variation in genome sequences. In this context it is necessary to know the statistical properties of empirical observables (such as the local homozygosity for instance). Previous work relies on numerical results or assumes Gaussian approximations for the corresponding distributions. In this paper we give an analytical derivation of the statistical properties of the local homozygosity and other empirical observables assuming selective neutrality. We find that such distributions can be very non-Gaussian.Comment: 4 pages, 4 figure

A two-directional approach to pyrrolizidines: total syntheses and biological evaluation of alkaloid cis-223B and (+/-)-xenovenine

Total syntheses of alkaloid cis-223B and xenovenine are reported in 3 and 4 steps respectively using a two-directional synthesis/triple reductive amination strategy, and their neurotoxic properties assessed

Lack of self-averaging in neutral evolution of proteins

We simulate neutral evolution of proteins imposing conservation of the thermodynamic stability of the native state in the framework of an effective model of folding thermodynamics. This procedure generates evolutionary trajectories in sequence space which share two universal features for all of the examined proteins. First, the number of neutral mutations fluctuates broadly from one sequence to another, leading to a non-Poissonian substitution process. Second, the number of neutral mutations displays strong correlations along the trajectory, thus causing the breakdown of self-averaging of the resulting evolutionary substitution process.Comment: 4 pages, 2 figure

Utterance Selection Model of Language Change

We present a mathematical formulation of a theory of language change. The theory is evolutionary in nature and has close analogies with theories of population genetics. The mathematical structure we construct similarly has correspondences with the Fisher-Wright model of population genetics, but there are significant differences. The continuous time formulation of the model is expressed in terms of a Fokker-Planck equation. This equation is exactly soluble in the case of a single speaker and can be investigated analytically in the case of multiple speakers who communicate equally with all other speakers and give their utterances equal weight. Whilst the stationary properties of this system have much in common with the single-speaker case, time-dependent properties are richer. In the particular case where linguistic forms can become extinct, we find that the presence of many speakers causes a two-stage relaxation, the first being a common marginal distribution that persists for a long time as a consequence of ultimate extinction being due to rare fluctuations.Comment: 21 pages, 17 figure