Biology subjects

Saber, S.

Publications and source records attributed to Saber, S..

8 recordsLinked to original sources

bioRxiv2025

Evolution of the rate, spectrum, and fitness effects of mutation under minimal selection in Caenorhabditis elegans

The rate, molecular spectrum, and fitness effects of mutations vary at all levels of the biological hierarchy, from within individual genomes to among taxonomic domains. Understanding the evolutionary factors underpinning that variation is of fundamental importance to biology. Accurate quantification of the properties of mutations requires that other evolutionary forces, especially natural selection, be minimized as much as possible. To investigate the evolution of the mutational process in C. elegans, we propagated a set of 100 "first order" mutation accumulation (O1MA) lines under minimal selection for [~]150 generations, divided each O1MA line into two "second order" MA (O2MA) lines and propagated them for another [~]150 generations, at which time the genome of each O2MA line was sequenced, and a subset of 50 O1MA families was assayed for competitive fitness. Over the course of the experiment, the mean nucleotide substitution mutation rate did not change, but the variance increased. In contrast, the indel mutation rate increased significantly. The two types of mutations fulfill the predictions of different theoretical models for the evolution of mutation rate. These results reinforce previous findings that the rate of indels is more sensitive to endogenous stress than the rate of nucleotide substitutions. Several evolutionary quandaries could be resolved if deleterious mutations interact synergistically (negative epistasis). Evidence for synergistic epistasis is famously inconclusive, although there is reason to think it may be more detectable under competitive conditions. However, a model of constant mutational effects on competitive fitness explains the results significantly better than a model including epistasis.

evolutionary biology↗

bioRxiv2025

Outcrossing Complicates Mutation Purging by Trapping Single Nucleotide Polymorphisms in Structural Variant Mutations

Classical mutational theories centered on single nucleotide polymorphisms suggest that outcrossing enhances the purging of deleterious mutations by promoting recombination. However, larger structural variants, such as insertions, deletions, and inversions, can suppress recombination and create linkage blocks. Using experimental evolution and whole-genome long- and short-read sequencing, we characterized structural and nucleotide mutation landscapes in three Caenorhabditis elegans strains following repeated mutagen exposure and recovery. We found substantial strain-specific differences in structural variant accumulation and mutation retention. The strain with the highest outcrossing propensity exhibited the greatest structural variant burden and a higher fraction of single nucleotide polymorphisms within structural variant intervals. Consistent with this pattern, our population genetic simulations showed that structural variants can persist more readily under higher outcrossing rates. Together, these results indicate that structural variant architecture may influence mutation retention dynamics and highlight strain-specific constraints on purging following mutagenesis in C. elegans.

bioinformatics↗

bioRxiv2025

Ultrasound-based prediction of spawning time in females of Octopus vulgaris

There has been a great interest in common octopus Octopus vulgaris aquaculture over recent years and commercial production is coming within reach. In addition, O. vulgaris is a short-lived semelparous species with a long spawning period. Therefore, monitoring ovary maturation in cultured octopuses can be useful in the scheduling of hatchery operations and management of culture resources. The present work aimed to assess the ovary maturity status in cultured and wild common octopus by means of a noninvasive technique, ultrasonography, to anticipate the time of spawning in aquaculture. A total of 27 octopuses (15 cultured and 12 wild ones) in different ovarian maturation stages were used in ultrasonographic procedures. Ultrasound-based ovary volumes were compared with real ovarian volumes and then the ultrasonography-based gonadosomatic index (GSIU) was estimated. Data from cultured females indicate that GSIU was initially below 0.3 cm3 per 100 g of body weight in immature animals, and attained a fast increase until reaching about 4.0 cm3 per 100 g of body weight right before spawning. The steep increase in relative volume occurred similarly in females of different body weights. In addition, the specific growth rate of cultured animals decreases with time, and with GSIU. Lastly, a linear mixed model indicated a significantly negative and logarithmic relationship between the time to spawning and GSIU in captive females. That relationship will be useful to predict spawning time in immature and maturing females, helping in the management of octopus broodstocks in research and production facilities.

zoology↗

bioRxiv2024

Direct inference of the distribution of fitness effects of spontaneous mutations from recombinant inbred C. elegans mutation accumulation lines

The distribution of fitness effects (DFE) of new mutations plays a central role in evolutionary biology. Estimates of the DFE from experimental Mutation Accumulation (MA) lines are compromised by the complete linkage disequilibrium (LD) between mutations in different lines. To reduce LD, we constructed two sets of recombinant inbred lines from a cross of two C. elegans MA lines. One set of lines ("RIAILs") was intercrossed for ten generations prior to ten generations of selfing; the second set of lines ("RILs") omitted the intercrossing. Residual LD in the RIAILs is much less than in the RILs, which affects the inferred DFE when the sets of lines are analyzed separately. The best-fit model estimated from all lines (RIAILs + RILs) infers a large fraction of mutations with positive effects ([~]40%); models that constrain mutations to have negative effects fit much worse. The conclusion is the same using only the RILs. For the RIAILs, however, models that constrain mutations to have negative effects fit nearly as well as models that allow positive effects. When mutations in high LD are pooled into haplotypes, the inferred DFE becomes increasingly negative-skewed and leptokurtic. We conclude that the conventional wisdom - most mutations have effects near zero, a handful of mutations have effects that are substantially negative and mutations with positive effects are very rare - is likely correct, and that unless it can be shown otherwise, estimates of the DFE that infer a substantial fraction of mutations with positive effects are likely confounded by LD.

evolutionary biology↗

bioRxiv2021

Mutation, selection, and the prevalence of the C. elegans mortal germline phenotype

C. elegans strains with the heat-sensitive mortal germline (Mrt) phenotype become progressively sterile over the course of a few tens of generations when maintained at temperatures near the upper range of C. elegans tolerance. Mrt is transgenerationally-heritable, and proximately under epigenetic control. Previous studies have suggested that Mrt presents a relatively large mutational target, and that Mrt is not uncommon in natural populations of C. elegans. The Mrt phenotype is not monolithic. Some strains exhibit a strong Mrt phenotype, in which individuals invariably become sterile over a few generations, whereas other strains show a weaker (less penetrant) phenotype in which the onset of sterility is slower and more stochastic. We present results in which we (1) quantify the rate of mutation to the Mrt phenotype, and (2) quantify the frequency of Mrt in a collection of 95 wild isolates. Over the course of ~16,000 meioses, we detected one mutation to a strong Mrt phenotype, resulting in a point estimate of the mutation rate UMrt{approx} 6x10-5/genome/generation. We detected no mutations to a weak Mrt phenotype. 6/95 wild isolates have a strong Mrt phenotype, and although quantification of the weak Mrt phenotype is inexact, the weak Mrt phenotype is not rare in nature. We estimate a strength of selection against mutations conferring the strong Mrt phenotype [Formula], similar to selection against mutations affecting competitive fitness. The appreciable frequency of weak Mrt variants in nature combined with the low mutation rate suggests that Mrt may be maintained by balancing selection.

genetics↗

bioRxiv2021

Mutation, selection, and quantitative genetic architecture of susceptibility to bacterial pathogens in C. elegans

Understanding the evolutionary and genetic underpinnings of susceptibility to pathogens is of fundamental importance across a wide swathe of biology. Much theoretical and empirical effort has focused on genetic variants of large effect, but pathogen susceptibility often appears to be a polygenic complex trait. Here we investigate the quantitative genetics of survival over 120 hours of exposure ("susceptibility") of C. elegans to three bacterial pathogens of varying virulence, along with the standard laboratory food, the OP50 strain of E. coli. We compare the genetic (co)variance input by spontaneous mutations accumulated under minimal selection to the standing genetic (co)variance in a set of 47 wild isolates. Three conclusions emerge. First, mutations increase susceptibility to pathogens, and susceptibility is uncorrelated with fitness in the absence of pathogens. Second, the orientation in trait space of the heritable (co)variance of wild isolates is sufficiently explained by mutation. However, with the possible exception of S. aureus, pathogen susceptibility is clearly under purifying, directional, selection of magnitude roughly similar to that of competitive fitness in the MA conditions. The results provide no evidence for fitness tradeoffs between pathogen susceptibility and fitness in the absence of pathogens.

evolutionary biology↗

bioRxiv2018

Head-to-Head Comparison of Three Methods of Quantifying Competitive Fitness in C. elegans

Organismal fitness is relevant in many contexts in biology. The most meaningful experimental measure of fitness is competitive fitness, when two or more entities (e.g., genotypes) are allowed to compete directly. In theory, competitive fitness is simple to measure: an experimental population is initiated with the different types in known proportions and allowed to evolve under experimental conditions to a predefined endpoint. In practice, there are several obstacles to obtaining robust estimates of competitive fitness in multicellular organisms, the most pervasive of which is simply the time it takes to count many individuals of different types from many replicate populations. Methods by which counting can be automated in high throughput are desirable, but for automated methods to be useful, the bias and technical variance associated with the method must be (a) known, and (b) sufficiently small relative to other sources of bias and variance to make the effort worthwhile.\n\nThe nematode Caenorhabditis elegans is an important model organism, and the fitness effects of genotype and environmental conditions are often of interest. We report a comparison of three experimental methods of quantifying competitive fitness, in which wild-type strains are competed against GFP-marked competitors under standard laboratory conditions. Population samples were split into three replicates and counted (1) \"by eye\" from a saved image, (2) from the same image using CellProfiler image analysis software, and (3) with a large particle flow cytometer (a \"worm sorter\"). From 720 replicate samples, neither the frequency of wild-type worms nor the among-sample variance differed significantly between the three methods. CellProfiler and the worm sorter provide at least a tenfold increase in sample handling speed with little (if any) bias or increase in variance.

evolutionary biology↗

bioRxiv2017

The mutational decay of male and hermaphrodite competitive fitness in the androdioecious nematode C. elegans, in which males are naturally rare

Androdioecious Caenorhabditis have a high frequency of self-compatible hermaphrodites and a low frequency of males. The effects of mutations on male fitness are of interest for two reasons. First, when males are rare, selection on male-specific mutations is less efficient than in hermaphrodites. Second, males may present a larger mutational target than hermaphrodites because of the different ways in which fitness accrues in the two sexes.\n\nWe report the first estimates of male-specific mutational effects in an androdioecious organism. The rate of male-specific inviable or sterile mutations is [≤] 5 x 10-4/generation, below the rate at which males would be lost solely due to those kinds of mutations. The rate of mutational decay of male competitive fitness is ~0.17%/generation; that of hermaphrodite competitive fitness is ~0.11%/generation. The point estimate of ~1.5X faster rate of mutational decay of male fitness is nearly identical to the same ratio in Drosophila. Estimates of mutational variance (VM) for male mating success and competitive fitness are not significantly different from zero, whereas VM for hermaphrodite competitive fitness is similar to that of non-competitive fitness. The discrepancy between the two sexes is probably due to the greater inherent variability of mating relative to internal self-fertilization.

evolutionary biology↗