Juan Antonio Rodríguez

Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European

Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.

Virtual Agents and 3D Virtual Worlds for Preserving and Simulating Cultures

Many researchers associate a culture with some form of knowledge; other scholars stress the importance of the environment inhabited by the knowledge carriers; while archaeologists learn about cultures through the objects produced in the environment as a result of utilizing this knowledge. In our work we propose a model of virtual culture that preserves the environment, objects and knowledge associated with a certain culture in a 3D Virtual World. We highlight the significance of virtual agents in our model as, on the one hand, being the knowledge carriers and, on the other hand, being an important element establishing the connection between the environment, objects and knowledge. For testing the resulting model we have developed a research prototype simulating the culture of the ancient City of Uruk 3000 B. C. (one of the first human-built cities on Earth) within a Virtual World of Second Life.

Developing virtual heritage applications as normative multiagent systems

The majority of existing virtual heritage applications are focused on detailed 3D reconstruction of historically significant sites and ancient artifacts. Recreating the way of life of ancient people is only considered by some researchers, who employ crowd simulation for this task. Existing crowd simulation algorithms are not suitable for modeling complex individual behaviors and role dependent agent interactions with other participants in the Virtual World. To address this problem we suggest treating 3D Virtual Worlds as Normative Multiagent Systems and propose the Virtual Institutions Methodology to be used for design and deployment of Virtual Worlds that require complex interactions involving both humans and autonomous agents. To highlight the usefulness of this approach we illustrate how Virtual Institutions are employed in the development of the Uruk prototype, which integrates 3D Virtual Worlds and Artificial Intelligence in the domain of cultural heritage.

Antagonistic pleiotropy and mutation accumulation influence human senescence and disease

Senescence has long been a public health challenge as well as a fascinating evolutionary problem. There is neither a universally accepted theory for its ultimate causes, nor a consensus about what may be its impact on human health. Here we test the predictions of two evolutionary explanations of senescence—mutation accumulation and antagonistic pleiotropy—which postulate that genetic variants with harmful effects in old ages can be tolerated, or even favoured, by natural selection at early ages. Using data from genome-wide association studies (GWAS), we study the effects of genetic variants associated with diseases appearing at different periods in life, when they are expected to have different impacts on fitness. Data fit theoretical expectations. Namely, we observe higher risk allele frequencies combined with large effect sizes for late-onset diseases, and detect a significant excess of early–late antagonistically pleiotropic variants that, strikingly, tend to be harboured by genes related to ageing. Beyond providing systematic, genome-wide evidence for evolutionary theories of senescence in our species and contributing to the long-standing question of whether senescence is the result of adaptation, our approach reveals relationships between previously unrelated pathologies, potentially contributing to tackling the problem of an ageing population.

Genomic analysis of the blood attributed to Louis XVI (1754–1793), king of France

A pyrographically decorated gourd, dated to the French Revolution period, has been alleged to contain a handkerchief dipped into the blood of the French king Louis XVI (1754–1793) after his beheading but recent analyses of living males from two Bourbon branches cast doubts on its authenticity. We sequenced the complete genome of the DNA contained in the gourd at low coverage (~2.5×) with coding sequences enriched at a higher ~7.3× coverage. We found that the ancestry of the gourds genome does not seem compatible with Louis XVIs known ancestry. From a functional perspective, we did not find an excess of alleles contributing to height despite being described as the tallest person in Court. In addition, the eye colour prediction supported brown eyes, while Louis XVI had blue eyes. This is the first draft genome generated from a person who lived in a recent historical period; however, our results suggest that this sample may not correspond to the alleged king.

Multi-agent simulation applied to on-line music distribution market

Over the past few years it has become clear that the Internet will play an ever greater role in the distribution of digital contents. Our main aim is to provide businesses in the digital contents sector with a tool, which enables them to take informed business strategy decisions and become more competitive by adapting their traditional business models to the new, demanding reality. To achieve this objective, we have implemented a first version of a music market model called SimWebA that is based on multiagent simulation technology. In our simulations, agents represent market stakeholders that act autonomously according to their interests and interact with other agents inside the market environment. This allows end users to investigate the implications of a variety of decisions and strategies by running simulations starting from different initial conditions.

Integrating genomics into evolutionary medicine

The application of the principles of evolutionary biology into medicine was suggested long ago and is already providing insight into the ultimate causes of disease. However, a full systematic integration of medical genomics and evolutionary medicine is still missing. Here, we briefly review some cases where the combination of the two fields has proven profitable and highlight two of the main issues hindering the development of evolutionary genomic medicine as a mature field, namely the dissociation between fitness and health and the still considerable difficulties in predicting phenotypes from genotypes. We use publicly available data to illustrate both problems and conclude that new approaches are needed for evolutionary genomic medicine to overcome these obstacles.

Genetic factors affecting EBV copy number in lymphoblastoid cell lines derived from the 1000 Genome Project samples

Epstein-Barr virus (EBV), human herpes virus 4, has been classically associated with infectious mononucleosis, multiple sclerosis and several types of cancers. Many of these diseases show marked geographical differences in prevalence, which points to underlying genetic and/or environmental factors. Those factors may include a different susceptibility to EBV infection and viral copy number among human populations. Since EBV is commonly used to transform B-cells into lymphoblastoid cell lines (LCLs) we hypothesize that differences in EBV copy number among individual LCLs may reflect differential susceptibility to EBV infection. To test this hypothesis, we retrieved whole-genome sequenced EBV-mapping reads from 1,753 LCL samples derived from 19 populations worldwide that were sequenced within the context of the 1000 Genomes Project. An in silico methodology was developed to estimate the number of EBV copy number in LCLs and validated these estimations by real-time PCR. After experimentally confirming that EBV relative copy number remains stable over cell passages, we performed a genome wide association analysis (GWAS) to try detecting genetic variants of the host that may be associated with EBV copy number. Our GWAS has yielded several genomic regions suggestively associated with the number of EBV genomes per cell in LCLs, unraveling promising candidate genes such as CAND1, a known inhibitor of EBV replication. While this GWAS does not unequivocally establish the degree to which genetic makeup of individuals determine viral levels within their derived LCLs, for which a larger sample size will be needed, it potentially highlighted human genes affecting EBV-related processes, which constitute interesting candidates to follow up in the context of EBV related pathologies.

A dynamic tool for finding redundant computations in native code

Compilers perform optimizations to improve application runtime performance, but they often fail to generate optimal code due to complicated interactions between optimizations and unforeseen interactions of optimizations with the target architecture. Although there exist performance monitoring tools that can collect CPU performance information via hardware event counters, compiler developers or performance analysts need to comprehensively interpret the information to infer deficiencies in compiler optimizations. This paper presents a tool that can identify potentially redundant computations relevant to specific compiler optimizations. In particular, our current implementation can identify redundant computations that match three patterns occurring in compiler generated native code: 1. redundant sign/zero extension, 2. redundant constant-spill, and 3. missing copy/constant propagation. Our tool adapts the Pin dynamic instrumentation framework to analyze program execution contexts at runtime and identify the redundant computations described above. We use this tool to report both locations and execution frequencies of redundant computations within the SPEC®CPU2006 benchmarks generated by two GCC compiler versions targeting IA-32 and Intel® 64 architectures. By effectively removing instrumentation that has become unnecessary, our tools runs at 19x the average execution time of these benchmarks. From this study, we are able to address how redundant computations are affected by different architectural features such as a number of registers and memory address size, and different compiler versions.

Replicability and Prediction: Lessons and Challenges from GWAS

Since the publication of the Wellcome Trust Case Control Consortium (WTCCC) landmark study a decade ago, genome-wide association studies (GWAS) have led to the discovery of thousands of risk variants involved in disease etiology. This success story has two angles that are often overlooked. First, GWAS findings are highly replicable. This is an unprecedented phenomenon in complex trait genetics, and indeed in many areas of science, which in past decades have been plagued by false positives. At a time of increasing concerns about the lack of reproducibility, we examine the biological and methodological reasons that account for the replicability of GWAS and identify the challenges ahead. In contrast to the exemplary success of disease gene discovery, at present GWAS findings are not useful for predicting phenotypes. We close with an overview of the prospects for individualized prediction of disease risk and its foreseeable impact in clinical practice.