Biology subjects

Peccoud, J.

Publications and source records attributed to Peccoud, J..

25 records · Page 2Linked to original sources

bioRxiv2019

Securing the exchange of synthetic genetic constructs using digital signatures

Synthetic biology relies on an ever-growing supply chain of synthetic genetic material. Technologies to secure the exchange of this material are still in their infancy. Solutions proposed thus far have focused on watermarks, a dated security approach that can be used to claim authorship, but is subject to counterfeit, and does not provide any information about the integrity of the genetic material itself. We describe how data encryption and digital signature algorithms can be used to ensure the integrity and authenticity of synthetic genetic constructs. Using a pilot software that generates digital signatures and other encrypted data for plasmids, we demonstrate that we can predictably extract information about the author, the identity, and the integrity of plasmid sequences from sequencing data alone without a reference sequence, all without compromising the function of the plasmids. We discuss how this technology can be improved, applied, and expanded to support the new bioeconomy.

synthetic biology↗

bioRxiv2019

Sex chromosomes control vertical transmission of feminizing Wolbachia symbionts in an isopod

Microbial endosymbiosis is widespread in animals, with major ecological and evolutionary implications. Successful symbiosis relies on efficient vertical transmission through host generations. However, when symbionts negatively affect host fitness, hosts are expected to evolve suppression of symbiont effects or transmission. Here we show that sex chromosomes control vertical transmission of feminizing Wolbachia endosymbionts in the isopod Armadillidium nasatum. Theory predicts that the invasion of an XY/XX species by cytoplasmic sex ratio distorters is unlikely because it leads to fixation of the unusual (and often lethal or infertile) YY genotype. We demonstrate that A. nasatum X and Y sex chromosomes are genetically highly similar and YY individuals are viable and fertile, thereby enabling Wolbachia spread in this XY-XX species. Nevertheless, we show that Wolbachia cannot drive fixation of YY individuals because infected YY females do not transmit Wolbachia to their offspring, unlike XX and XY females. The genetic basis fits the model of a Y-linked recessive allele (associated with an X-linked dominant allele), in which the homozygous state suppresses Wolbachia transmission. Moreover, production of all-male progenies by infected YY females restores a balanced sex ratio at the host population level. This suggests that blocking of Wolbachia transmission by YY females may have evolved to suppress feminization, thereby offering a whole new perspective on the evolutionary interplay between microbial symbionts and host sex chromosomes.

evolutionary biology↗

bioRxiv2019

A Hybrid Stochastic Model of the Budding Yeast Cell Cycle

The growth and division of eukaryotic cells are regulated by complex, multi-scale networks. In this process, the mechanism controlling cell cycle progression has to be robust against inherent noise in the system. In this paper, a hybrid stochastic model is developed to study the effects of noise on the control mechanism of the budding yeast cell cycle. The modeling approach leverages, in a single multi-scale model, the advantages of two regimes: 1) the computational efficiency of a deterministic approach, and 2) the accuracy of stochastic simulations. Our results show that this hybrid stochastic model achieves high computational efficiency while generating simulation results that match very well with published experimental measurements.

systems biology↗

bioRxiv2019

A stochastic model for error correction of kinetochore-microtubule attachments and its coupling to the spindle assembly checkpoint

To divide replicated chromosomes equally between daughter cells kinetochores must attach to microtubules emanating from opposite poles of the mitotic spindle. Two mechanisms, namely, error correction and spindle assembly checkpoint work together to facilitate this process. The error correction mechanism recognizes and detaches erroneous kinetochore-microtubule attachments, and the spindle assembly checkpoint delays the onset of anaphase until all the kinetochores are properly attached. Kinases and phosphatases at the kinetochore play a key role in proper functioning of these two mechanisms. Here we present a stochastic model to study how the opposing activities of kinases and phosphatases at the kinetochore affect error correction of kinetochore-microtubule attachments and checkpoint signaling in budding yeast, Saccharomyces cerevisiae. We show that error correction and biorientation of chromosomes occurs efficiently when the ratio between kinase activity of Ipl1 and the activity of an opposing phosphatase is a constant (balance point), and derive an approximate analytical formula that defines the balance point. Analysis of the coupling of the spindle assembly checkpoint signal to error correction shows that its strength remains high when the Ipl1 activity is equal to (or larger than) the value specified by the balance point, and the activity of another kinase, Mps1, is much larger (approximately 30 times larger) than its opposing phosphatase (PP1). We also find that the geometrical orientation of sister chromatids does not significantly improve the probability of their reaching biorientation, which depends entirely on Ipl1-dependent microtubule detachment. Author summaryThe kinetochore, the master regulator of chromosome segregation, integrates signals from different chromosome attachment states to generate an appropriate response, like the destabilization of erroneous kinetochore-microtubule attachments, stabilization of correct attachments, maintenance of the spindle assembly checkpoint signal until all kinetochores are properly attached, and finally silencing of checkpoint when biorientation is achieved. At a molecular level the job is carried out by kinases and phosphatases. The complexity of the interactions between these kinases and phosphatases makes intuitive analysis of the control network impossible, and a systems-level model is needed to put experimental information together and to generate testable hypotheses. Here we present such a model for the process of error correction and its coupling to the spindle assembly checkpoint in budding yeast. Using the model, we characterize the balance between kinase and phosphatase activities required for removing erroneous attachments and then establishing correct stable attachments between kinetochore and microtubule. We also analyze how the balance affects the strength of the spindle assembly checkpoint signal.

systems biology↗

bioRxiv2019

Challenges and opportunities for strain verification by whole-genome sequencing

Laboratory strains, cell lines, and other genetic materials change hands frequently in the life sciences. Despite evidence that such materials are subject to mix-ups, contamination, and accumulation of secondary mutations, verification of strains and samples is not an established part of many experimental workflows. With the plummeting cost of next generation technologies, it is conceivable that whole genome sequencing (WGS) could be applied to routine strain and sample verification in the future. To demonstrate the need for strain validation by WGS, we sequenced haploid yeast segregants derived from a popular commercial mutant collection and identified several unexpected mutations. We determined that available bioinformatics tools may be ill-suited for verification and highlight the importance of finishing reference genomes for commonly-used laboratory strains.

bioinformatics↗

bioRxiv2018

A framework for estimating the effects of sequential reproductive barriers: implementation using Bayesian models with field data from cryptic species

Determining how reproductive barriers modulate gene flow between populations represents a major step towards understanding the factors shaping the course of speciation. Although many indices quantifying reproductive isolation (RI) have been proposed, they do not permit the quantification of cross direction-specific RI under varying species frequencies and over arbitrary sequences of barriers. Furthermore, techniques quantifying associated uncertainties are lacking, and statistical methods unrelated to biological process are still preferred for obtaining confidence intervals and p-values. To address these shortcomings, we provide new RI indices that model changes in gene flow for both directions of hybridization, and we implement them in a Bayesian model. We use this model to quantify RI between two species of the psyllid Cacopsylla pruni based on field genotypic data for mating individuals, inseminated spermatophores and progeny. The results showed that pre-insemination isolation was strong, mildly asymmetric and undistinguishably different between study sites despite large differences in species frequencies; that post-insemination isolation strongly affected the more common hybrid type; and that cumulative isolation was close to complete. In the light of these results, we discuss how these developments can strengthen comparative RI studies.\n\nAuthor contributionsJP and NS initiated the study and obtained biological data. JP and DRJP developed the porosity-based approach. DRJP conceived the Bayesian implementation and code. JP, DRJP and NS wrote the manuscript.\n\nData availabilityMitochondrial sequence data will be available at Genbank, source code is available at xxx.

evolutionary biology↗

bioRxiv2017

Disentangling The Causes For Faster-X Evolution In Aphids

Faster evolution of X chromosomes has been documented in several species and results from the increased efficiency of selection on recessive alleles in hemizygous males and/or from increased drift due to the smaller effective population size of X chromosomes. Aphids are excellent models for evaluating the importance of selection in faster-X evolution, because their peculiar life-cycle and unusual inheritance of sex-chromosomes lead to equal effective population sizes for X and autosomes. Because we lack a high-density genetic map for the pea aphid whose complete genome has been sequenced, we assigned its entire genome to the X and autosomes based on ratios of sequencing depth in males and females. Unexpectedly, we found frequent scaffold misassembly, but we could unambiguously locate 13,726 genes on the X and 19,263 on autosomes. We found higher non-synonymous to synonymous substitutions ratios (dN/dS) for X-linked than for autosomal genes. Our analyses of substitution rates together with polymorphism and expression data showed that relaxed selection is likely to contribute predominantly to faster-X as a large fraction of X-linked genes are expressed at low rates and thus escape selection. Yet, a minor role for positive selection is also suggested by the difference between substitution rates for X and autosomes for male-biased genes (but not for asexual female-biased genes) and by lower Tajimas D for X-linked than for autosomal genes with highly male-biased expression patterns. This study highlights the relevance of organisms displaying alternative inheritance of chromosomes to the understanding of forces shaping genome evolution.

evolutionary biology↗