Biology subjects

Siri-Jegousse, A.

Publications and source records attributed to Siri-Jegousse, A..

7 recordsLinked to original sources

bioRxiv2026

TMRCA is observable from the branch lengths of a coalescent

The height of ancestral trees, in other words the time to the most recent common ancestor in a genealogical tree, is an informative statistic in population genomics and used in contexts of genealogical dating, demographic history inference, and assessing signals of selection. Exploiting a general pathwise identity between the height of a tree and its branch lengths, we revisit Zeng et al.s mutation rate estimator to develop a model-free estimator for the product of the expected height of genealogical trees with the scaled mutation rate, both for single loci and genomic regions. This estimator is a linear function of the site frequency spectrum of a sample, i.e., of the distribution of allele counts at all segregating sites across the locus or genomic region and thus both observable and computationally cheap. We show that, under the infinite sites model of mutation, our estimator is unbiased and, for two genome-wide models of ancestries (sequential Markovian coalescents and common-pedigree ancestries), consistent. Furthermore, we show via simulation that our estimator performs smaller errors than averaging over reconstructed ancestral tree heights (extracted from reconstructed ancestral recombination graphs) when considering genome properties similar to human genomes across large genomic regions. We then revisit a publicly available genomic dataset of dogs and wolves and compare our method with extracting TMRCAs from ancestral recombination graph reconstructions.

genetics↗

bioRxiv2024

The TMRCA of general genealogies in populations of variable size

We study the time to the most recent common ancestor (TMRCA) of a sample of finite size in a wide class of genealogical models for populations with deterministically varying size. This is made possible by recently developed results on inhomogeneous phase-type random variables, allowing us to obtain the density and the moments of the TMRCA of time-dependent coalescent processes in terms of matrix formulas. We also provide matrix simplifications permitting a more straightforward calculation. With these results, the TMRCA provides an explanatory variable to distinguish different evolutionary scenarios, and to infer model parameters.

evolutionary biology↗

bioRxiv2023

Estimating the Lambda measure in multiple-merger coalescents

Multiple-merger coalescents, also known as {Lambda}-coalescents, have been used to describe the genealogy of populations that have a skewed offspring distribution or that undergo strong selection. Inferring the characteristic measure {Lambda}, which describes the rates of the multiple-merger events, is key to understand these processes. So far, most inference methods only work for some particular families of {Lambda}-coalescents that are described by only one parameter, but not for more general models. This article is devoted to the construction of a non-parametric estimator of the density of {Lambda} that is based on the observation at a single time of the so-called Site Frequency Spectrum (SFS), which describes the allelic frequencies in a present population sample. First, we produce estimates of the multiple-merger rates by solving a linear system, whose coefficients are obtained by appropriately subsampling the SFS. Then, we use a technique that aggregates the information extracted from the previous step through a kernel type of re-construction to give a non-parametric estimation of the measure {Lambda}. We give a consistency result of this estimator under mild conditions on the behavior of {Lambda} around 0. We also show some numerical examples of how our method performs.

evolutionary biology↗

bioRxiv2022

Plasmid stability in fluctuating environments:population genetics of multi-copy plasmids

Plasmids are extra-chromosomal genetic elements that encode a wide variety of phenotypes and can be maintained in bacterial populations through vertical and horizontal transmission, thus increasing bacterial adaptation to hostile environmental conditions like those imposed by antimicrobial sub-stances. To circumvent the segregational instability resulting from randomly distributing plasmids between daughter cells upon division, non-transmissible plasmids tend to be carried in multiple copies per cell, with the added benefit of exhibiting increased gene dosage and resistance levels. But carrying multiple copies also results in a high metabolic burden to the bacterial host, therefore reducing the overall fitness of the population. This trade-off poses an existential question for plasmids: What is the optimal plasmid copy number? In this manuscript, we address this question by postulating and analyzing a population genetics model to evaluate the interaction between selective pressure, the number of plasmid copies carried by each cell, and the metabolic burden associated with plasmid bearing in the absence of selection for plasmid-encoded traits. Parameter values of the model were estimated experimentally using Escherichia coli K12 carrying a multicopy plasmid encoding for a fluorescent protein and blaTEM-1, a gene conferring resistance to {beta}-lactam antibiotics. By numerically determining the optimal plasmid copy number for constant and fluctuating selection regimes, we show that plasmid copy number is a highly optimized evolutionary trait that depends on the rate of environmental fluctuation and balances the benefit between increased stability in the absence of selection with the burden associated with carrying multiple copies of the plasmid.

evolutionary biology↗

bioRxiv2019

Site Frequency Spectrum of the Bolthausen-Sznitman coalescent

We derive explicit formulas for the two first moments of he site frequency spectrum (SFSn,b)1[≤]b[≤]n-1 of the Bolthausen-Sznitman coalescent along with some precise and efficient approximations, even for small sample sizes n. These results provide new L2-asymptotics for some values of b = o(n). We also study the length of internal branches carrying b > n/2 individuals. In this case we obtain the distribution function and a convergence in law. Our results rely on the random recursive tree construction of the Bolthausen-Sznitman coalescent.

genetics↗

bioRxiv2019

Distinguishing coalescent models - which statistics matter most?

Modelling genetic diversity needs an underlying genealogy model. To choose a fitting model based on genetic data, one can perform model selection between classes of genealogical trees, e.g. Kingmans coalescent with exponential growth or multiple merger coalescents. Such selection can be based on many different statistics measuring genetic diversity. A random forest based Approximate Bayesian Computation is used to disentangle the effects of different statistics on distinguishing between various classes of genealogy models. For the specific question of inferring whether genealogies feature multiple mergers, a new statistic, the minimal observable clade size, is introduced. When combined with classical site frequency based statistics, it reduces classification errors considerably.

evolutionary biology↗

bioRxiv2018

Phase-type distributions in population genetics

Probability modelling for DNA sequence evolution is well established and provides a rich framework for understanding genetic variation between samples of individuals from one or more populations. We show that both classical and more recent models for coalescence (with or without recombination) can be described in terms of the so-called phase-type theory, where complicated and tedious calculations are circumvented by the use of matrices. The application of phase-type theory consists of describing the stochastic model as a Markov model by appropriately setting up a state space and calculating the corresponding intensity and reward matrices. Formulae of interest are then expressed in terms of these aforementioned matrices. We illustrate this by a few examples calculating the mean, variance and even higher order moments of the site frequency spectrum in the multiple merger coalescent models, and by analysing the mean and variance for the number of segregating sites for multiple samples in the two-locus ancestral recombination graph. We believe that phase-type theory has great potential as a tool for analysing probability models in population genetics. The compact matrix notation is useful for clarification of current models, in particular their formal manipulation (calculation), but also for further development or extensions.

bioinformatics↗