Planktonic foraminiferal ecozones: response of the pelagic environment to palaeoclimatic changes in the eastern Mediterranean Sea

A detailed study of the planktonic environment of the eastern Mediterranean Sea has permitted the reconstruction of the climatic history of this part of the basin during the time span from 9.7 to 6.6 Ma. The eastern Mediterranean Sea is confirmed as having a strong sensitivity to the climatic changes that occurred during that timespan. One of the very few complete hemipelagic successions of the Upper Miocene in Mediterranean is found in Gavdos island (SW Crete). Quantitative and qualitative modifications of the planktonic foraminiferal communities observed in Metochia section exhibit a sequence of biological events summarized in 11 successive main time intervals. The bioevents are defined by frequency peaks and/or local (re)-occurrences or (temporary) disappearances of some of the taxa, in association with more or less important fluctuations of the more common species. The planktonic foraminifera show a strong correlation with sea surface temperature variations and with changes in the physical and chemical properties of the upper water column caused by the climatic instability. Two prominent shifts in faunal parameters divide the period recorded in Metochia section into three major time slices that are discussed in chronological order: a cooling trend from 9,7 to 7,6 Ma, a warmer period from 7,6 to 7,2 Ma and then a cooling trend which finishes at the Messinian

Rates of SARS-COV-2 transmission and vaccination impact the fate of vaccine-resistant strains

Se considera que las vacunas son la mejor solución para controlar la actual pandemia por SARS-CoV-2. Sin embargo, la proliferación de cepas resistentes a las vacunas puede ser demasiado rápida para que su aplicación alivie la propagación de la pandemia, así como sus consecuencias económicas y sociales. Para cuantificar y caracterizar el riesgo de este escenario, utilizamos un modelo SIR con una dinámica estocástica para estudiar la probabilidad de aparición y transmisión de cepas resistentes a la vacuna. Usando parámetros que repliquen de manera realista la transmisión del SARS-CoV-2, modelizamos el patrón en forma de olas de la pandemia y consideramos el impacto que el ritmo de vacunación y la intensidad de las medidas de contención adoptadas tienen sobre la probabilidad de aparición de cepas resistentes a la vacuna. Como era de esperar, un ritmo rápido de vacunación disminuye la probabilidad de aparición de una cepa resistente a la vacuna. Sin embargo, aunque en principio pueda parecer contraintuitivo, cuando se produce una relajación de las restricciones en el momento en el que la mayoría de la población ya ha sido vacunada, la probabilidad de aparición de una cepa resistente a la vacuna aumenta considerablemente. En consecuencia, un período de contención estricta de la transmisión cerca del final de la campaña de vacunación puede reducir sustancialmente la probabilidad del establecimiento de cepas resistentes a la vacuna. Estos resultados, por tanto, sugieren la conveniencia de mantener las medidas y los protocolos de prevención durante toda la duración de la campaña de vacunación.Vaccines are thought to be the best available solution for controlling the ongoing SARS-CoV-2 pandemic. However, the emergence of vaccine-resistant strains may come too rapidly for current vaccine developments to alleviate the health, economic and social consequences of the pandemic. To quantify and characterize the risk of such a scenario, we created a SIR-derived model with initial stochastic dynamics of the vaccine-resistant strain to study the probability of its emergence and establishment. Using parameters realistically resembling SARS-CoV-2 transmission, we model a wave-like pattern of the pandemic and consider the impact of the rate of vaccination and the strength of non-pharmaceutical intervention measures on the probability of emergence of a resistant strain. As expected, we found that a fast rate of vaccination decreases the probability of emergence of a resistant strain. Counterintuitively, when a relaxation of non-pharmaceutical interventions happened at a time when most individuals of the population have already been vaccinated the probability of emergence of a resistant strain was greatly increased. Consequently, we show that a period of transmission reduction close to the end of the vaccination campaign can substantially reduce the probability of resistant strain establishment. These results, therefore, suggest the convenience of maintaining non-pharmaceutical interventions and prevention protocols throughout the entire vaccination period

The molecular basis, genetic control and pleiotropic effects of local gene co-expression.

Nearby genes are often expressed as a group. Yet, the prevalence, molecular mechanisms and genetic control of local gene co-expression are far from being understood. Here, by leveraging gene expression measurements across 49 human tissues and hundreds of individuals, we find that local gene co-expression occurs in 13% to 53% of genes per tissue. By integrating various molecular assays (e.g. ChIP-seq and Hi-C), we estimate the ability of several mechanisms, such as enhancer-gene interactions, in distinguishing gene pairs that are co-expressed from those that are not. Notably, we identify 32,636 expression quantitative trait loci (eQTLs) which associate with co-expressed gene pairs and often overlap enhancer regions. Due to affecting several genes, these eQTLs are more often associated with multiple human traits than other eQTLs. Our study paves the way to comprehend trait pleiotropy and functional interpretation of QTL and GWAS findings. All local gene co-expression identified here is available through a public database ( https://glcoex.unil.ch/ )

Assessing allele-specific expression across multiple tissues from RNA-seq read data

Motivation: RNA sequencing enables allele-specific expression (ASE) studies that complement standard genotype expression studies for common variants and, importantly, also allow measuring the regulatory impact of rare variants. The Genotype-Tissue Expression (GTEx) project is collecting RNA-seq data on multiple tissues of a same set of individuals and novel methods are required for the analysis of these data. Results: We present a statistical method to compare different patterns of ASE across tissues and to classify genetic variants according to their impact on the tissue-wide expression profile. We focus on strong ASE effects that we are expecting to see for protein-truncating variants, but our method can also be adjusted for other types of ASE effects. We illustrate the method with a real data example on a tissue-wide expression profile of a variant causal for lipoid proteinosis, and with a simulation study to assess our method more generally. Availability and implementation: http://www.well.ox.ac.uk/~rivas/mamba/. R-sources and data examples http://www.iki.fi/mpirinen/ Contact: [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

The effect of genetic variation on promoter usage and enhancer activity.

The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification remains challenging. Here, we use natural genetic variation and CAGE transcriptomes from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals, to map 5376 and 110 regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs), respectively. We characterize five categories of genes associated with puQTLs, distinguishing single from multi-promoter genes. Among multi-promoter genes, we find puQTL effects either specific to a single promoter or to multiple promoters with variable effect orientations. Regulatory variants associated with opposite effects on different mRNA isoforms suggest compensatory mechanisms occurring between alternative promoters. Our analyses identify differential promoter usage and modulation of enhancer activity as molecular mechanisms underlying eQTLs related to regulatory elements

Time-dependent genetic effects on gene expression implicate aging processes

Gene expression is dependent on genetic and environmental factors. In the last decade, a large body of research has significantly improved our understanding of the genetic architecture of gene expression. However, it remains unclear whether genetic effects on gene expression remain stable over time. Here, we show, using longitudinal whole-blood gene expression data from a twin cohort, that the genetic architecture of a subset of genes is unstable over time. In addition, we identified 2213 genes differentially expressed across time points that we linked with aging within and across studies. Interestingly, we discovered that most differentially expressed genes were affected by a subset of 77 putative causal genes. Finally, we observed that putative causal genes and down-regulated genes were affected by a loss of genetic control between time points. Taken together, our data suggest that instability in the genetic architecture of a subset of genes could lead to widespread effects on the transcriptome with an aging signature

Large-Scale Population Study of Human Cell Lines Indicates that Dosage Compensation Is Virtually Complete

X chromosome inactivation in female mammals results in dosage compensation of X-linked gene products between the sexes. In humans there is evidence that a substantial proportion of genes escape from silencing. We have carried out a large-scale analysis of gene expression in lymphoblastoid cell lines from four human populations to determine the extent to which escape from X chromosome inactivation disrupts dosage compensation. We conclude that dosage compensation is virtually complete. Overall expression from the X chromosome is only slightly higher in females and can largely be accounted for by elevated female expression of approximately 5% of X-linked genes. We suggest that the potential contribution of escape from X chromosome inactivation to phenotypic differences between the sexes is more limited than previously believed

Epistatic Interactions Alter Dynamics of Multilocus Gene-for-Gene Coevolution

Fitness costs associated with resistance or virulence genes are thought to play a key role in determining the dynamics of gene-for-gene (GFG) host-parasite coevolution. However, the nature of interactions between fitness effects of multiple resistance or virulence genes (epistasis) has received less attention. To examine effects of the functional form of epistasis on the dynamics of GFG host-parasite coevolution we modified a classic multilocus GFG model framework. We show that the type of epistasis between virulence genes largely determines coevolutionary dynamics, and that coevolutionary fluctuations are more likely with acceleratingly costly (negative) than with linear or deceleratingly costly (positive) epistasis. Our results demonstrate that the specific forms of interaction between multiple resistance or virulence genes are a crucial determinant of host-parasite coevolutionary dynamics

Evolutionary Comparison Provides Evidence for Pathogenicity of RMRP Mutations

Cartilage-hair hypoplasia (CHH) is a pleiotropic disease caused by recessive mutations in the RMRP gene that result in a wide spectrum of manifestations including short stature, sparse hair, metaphyseal dysplasia, anemia, immune deficiency, and increased incidence of cancer. Molecular diagnosis of CHH has implications for management, prognosis, follow-up, and genetic counseling of affected patients and their families. We report 20 novel mutations in 36 patients with CHH and describe the associated phenotypic spectrum. Given the high mutational heterogeneity (62 mutations reported to date), the high frequency of variations in the region (eight single nucleotide polymorphisms in and around RMRP), and the fact that RMRP is not translated into protein, prediction of mutation pathogenicity is difficult. We addressed this issue by a comparative genomic approach and aligned the genomic sequences of RMRP gene in the entire class of mammals. We found that putative pathogenic mutations are located in highly conserved nucleotides, whereas polymorphisms are located in non-conserved positions. We conclude that the abundance of variations in this small gene is remarkable and at odds with its high conservation through species; it is unclear whether these variations are caused by a high local mutation rate, a failure of repair mechanisms, or a relaxed selective pressure. The marked diversity of mutations in RMRP and the low homozygosity rate in our patient population indicate that CHH is more common than previously estimated, but may go unrecognized because of its variable clinical presentation. Thus, RMRP molecular testing may be indicated in individuals with isolated metaphyseal dysplasia, anemia, or immune dysregulation