Biology subjects

Baer, C. F.

Publications and source records attributed to Baer, C. F..

4 recordsLinked to original sources

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↗

bioRxiv2018

Tempo, mode, and fitness effects of mutation in Caenorhabditis elegans over 400 generations of minimal selection

The mutational process varies at many levels, from within genomes to among taxa. Many mechanisms have been linked to variation in mutation, but understanding of the evolution of the mutational process is rudimentary. Physiological condition is often implicated as a source of variation in microbial mutation rate and may contribute to mutation rate variation in multicellular organisms.\n\nDeleterious mutations are a ubiquitous source of variation in condition. We test the hypothesis that the mutational process depends on the underlying mutation load in two groups of Caenorhabditis elegans mutation accumulation (MA) lines that differ in their starting mutation loads. \"First-Order MA\" (O1MA) lines maintained under minimal selection for [~]250 generations were divided into high-fitness and low-fitness groups and sets of \"second-order MA\" (O2MA) lines derived from each O1MA line were maintained for [~]150 additional generations. Genomes of 48 O2MA lines and their progenitors were sequenced. There is significant variation among O2MA lines in base-substitution rate ({micro}bs), but no effect of initial fitness, whereas the indel rate is greater in high-fitness O2MA lines. Overall, {micro}bs is positively correlated with recombination and proximity to short tandem repeats and negatively correlated with 10 bp and 1 Kb GC content. However, probability of mutation is well-predicted by the three-nucleotide motif. [~]90% of the variance in standing nucleotide variation is explained by mutability. Total mutation rate increased in the O2MA lines, as predicted by the \"drift barrier\" model of mutation rate evolution. These data, combined with experimental estimates of fitness, suggest that epistasis is synergistic.

evolutionary biology↗

bioRxiv2017

Network Architecture and Mutational Sensitivity of the C. elegans Metabolome

A fundamental issue in evolutionary systems biology is understanding the relationship between the topological architecture of a biological network, such as a metabolic network, and the evolution of the network. The rate at which an element in a metabolic network accumulates genetic variation via new mutations depends on both the size of the mutational target it presents and its robustness to mutational perturbation. Quantifying the relationship between topological properties of network elements and the mutability of those elements will facilitate understanding the variation in and evolution of networks at the level of populations and higher taxa.\n\nWe report an investigation into the relationship between two topological properties of 29 metabolites in the C. elegans metabolic network and the sensitivity of those metabolites to the cumulative effects of spontaneous mutation. The relationship between several measures of network centrality and sensitivity to mutation is weak, but point estimates of the correlation between network centrality and mutational variance are positive, with only one exception. There is a marginally significant correlation between core number and mutational heritability. There is a small but significant negative correlation between the shortest path length between a pair of metabolites and the mutational correlation between those metabolites.\n\nPositive association between the centrality of a metabolite and its mutational heritability is consistent with centrally-positioned metabolites presenting a larger mutational target than peripheral ones, and is inconsistent with centrality conferring mutational robustness, at least in toto. The weakness of the correlation between shortest path length and the mutational correlation between pairs of metabolites suggests that network locality is an important but not overwhelming factor governing mutational pleiotropy. These findings provide necessary background against which the effects of other evolutionary forces, most importantly natural selection, can be interpreted.

systems 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↗