Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userSurvival of the densest accounts for the expansion of mitochondrial mutations in ageing
68
0
0.0
(
0
)
Added by
Ferdinando Insalata
Publication date
2020
fields
Biology
and research's language is
English
Ask ChatGPT about the research
No Arabic abstract
The expansion of deleted mitochondrial DNA (mtDNA) molecules has been linked to ageing, particularly in skeletal muscle fibres; its mechanism has remained unclear for three decades. Previous accounts assigned a replicative advantage to the deletions, but there is evidence that cells can, instead, selectively remove defective mtDNA. We present a spatial model that, without a replicative advantage, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with wave speed consistent with experimental data, unlike a standard model based on replicative advantage. We provide a formula that predicts that the wave speed drops with copy number, in agreement with experimental data. Crucially, our model yields travelling waves of mutants even if mutants are preferentially eliminated. Justified by this exemplar of how noise, density and spatial structure affect muscle ageing, we introduce the mechanism of stochastic survival of the densest, an alternative to replicative advantage, that may underpin other phenomena, like the evolution of altruism.
rate research
Read More
Levy flights in the space of mutations model time evolution of bacterial DNA. Parameters in the model are adjusted in order to fit observations coming from the Long Time Evolution Experiment with E. Coli.
Establishing the conditions that guarantee the spreading or the sustenance of altruistic traits in a population is the main goal of intergroup selection models. Of particular interest is the balance of the parameters associated to group size, migration and group survival against the selective advantage of the non-altruistic individuals. Here we use Kimuras diffusion model of intergroup selection to determine those conditions in the case the group survival probability is a nonlinear non-decreasing function of the proportion of altruists in a group. In the case this function is linear, there are two possible steady states which correspond to the non-altruistic and the altruistic phases. At the discontinuous transition line separating these phases there is a non-ergodic coexistence phase. For a continuous concave survival function, we find an ergodic coexistence phase that occupies a finite region of the parameter space in between the altruistic and the non-altruistic phases, and is separated from these phases by continuous transition lines. For a convex survival function, the coexistence phase disappears altogether but a bistable phase appears for which the choice of the initial condition determines whether the evolutionary dynamics leads to the altruistic or the non-altruistic steady state.
Motivated by the classical Susceptible-Infected-Recovered (SIR) epidemic models proposed by Kermack and Mckendrick, we consider a class of stochastic compartmental dynamical systems with a notion of partial ordering among the compartments. We call such systems unidirectional Mass Transfer Models (MTMs). We show that there is a natural way of interpreting a uni-directional MTM as a Survival Dynamical System (SDS) that is described in terms of survival functions instead of population counts. This SDS interpretation allows us to employ tools from survival analysis to address various issues with data collection and statistical inference of unidirectional MTMs. In particular, we propose and numerically validate a statistical inference procedure based on SDS-likelihoods. We use the SIR model as a running example throughout the paper to illustrate the ideas.
In a recent paper, Klaere et al. modeled the impact of substitutions on arbitrary branches of a phylogenetic tree on an alignment site by the so-called One Step Mutation (OSM) matrix. By utilizing the concept of the OSM matrix for the four-state nucleotide alphabet, Nguyen et al. presented an efficient procedure to compute the minimal number of substitutions needed to translate one alignment site into another.The present paper delivers a proof for this computation.Moreover, we provide several mathematical insights into the generalization of the OSM matrix to multistate alphabets.The construction of the OSM matrix is only possible if the matrices representing the substitution types acting on the character states and the identity matrix form a commutative group with respect to matrix multiplication. We illustrate a means to establish such a group for the twenty-state amino acid alphabet and critically discuss its biological usefulness.
Data from a long time evolution experiment with Escherichia Coli and from a large study on copy number variations in subjects with european ancestry are analyzed in order to argue that mutations can be described as Levy flights in the mutation space. These Levy flights have at least two components: random single-base substitutions and large DNA rearrangements. From the data, we get estimations for the time rates of both events and the size distribution function of large rearrangements.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
