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[
J Exp Zool B Mol Dev Evol,
2007]
The free-living nematode Caenorhabditis elegans is distributed globally and found in many varied habitats. However, in comparison to our understanding of the genetics of the species, little is known about natural variation and many major life history traits appear to show only limited differences between isolates. Here we show that temperature affects the lifetime fecundity and the reproductive timing of C. elegans and that there is a genotype by environment interaction, with isolates varying in how lifetime fecundity changes with temperature. We show that the lower lifetime fecundity observed at higher temperatures is primarily due to a reduction in the number of functional sperm. Further, isolates vary in their lifetime fecundity because of inter-isolate differences in this effect of temperature on the number of functional sperm. J. Exp. Zool. (Mol. Dev. Evol.) 308B, 2007. (c) 2007 Wiley-Liss, Inc.
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[
Evolution,
2006]
The pattern and extent of pleiotropic gene action can contribute substantially to the internal structure and shape of the additive genetic variance-covariance matrix (G)--a key determinant of evolutionary trajectories. We use data from our study (Estes et al. 2004) on the univariate effects of mutation in a mismatch-repair-defective strain,
msh-2, of Caenorhabditis elegans to address the impact of increasing levels of selection on the magnitude and pattern of genetic covariance due to new mutations. Mutational covariances between three life-history traits are shown to exhibit a weak pattern of decline with increasing population size (increasing selection), while the orientation of mutational matrices remains reasonably constant. This suggests that mutations with smaller effects on fitness may tend to be slightly more confined in their influence than large-effect mutations (i.e., small-effect mutations reduce the magnitude of covariation between characters), but do not change the direction of this covariation.
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[
G3 (Bethesda),
2022]
Because of pleiotropy, mutations affect the expression and inheritance of multiple traits and, together with selection, are expected to shape standing genetic covariances between traits and eventual phenotypic divergence between populations. It is therefore important to find if the M matrix, describing mutational variances of each trait and covariances between traits, varies between genotypes. We here estimate theMmatrix for six locomotion behavior traits in lines of two genotypes of the nematode Caenorhabditis elegans that accumulated mutations in a nearly-neutral manner for 250 generations. We find significant mutational variance along at least one phenotypic dimension of the M matrices, but neither their size nor their orientation had detectable differences between genotypes. The number of generations of mutation accumulation, or the number of MA lines measured, was likely insufficient to sample enough mutations and detect potentially small differences between the two M matrices. We then tested if the M matrices were similar to one G matrix describing the standing genetic (co)variances of a population derived by the hybridization of several genotypes, including the two measured for M, and domesticated to a lab-defined environment for 140 generations. We found that the M and G were different because the genetic covariances caused by mutational pleiotropy in the two genotypes are smaller than those caused by linkage disequilibrium in the lab population. We further show that M matrices differed in their alignment with the lab population G matrix. If generalized to other founder genotypes of the lab population, these observations indicate that selection does not shape the evolution of the M matrix for locomotion behavior in the short-term of a few tens to hundreds of generations and suggests that the hybridization of C. elegans genotypes allows selection on new phenotypic dimensions of locomotion behavior.
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Environ Toxicol Chem,
2020]
Performing toxicity testing on multiple species with differing degrees of evolutionary relatedness can provide important information on how chemical sensitivity varies among species and can help pinpoint the biological drivers of species sensitivity. Such knowledge could ultimately be used to design better multi-species predictive ecological risk assessment models and identify particularly sensitive species. However, laboratory toxicity tests involving multiple species can also be resource intensive, especially when each species has unique husbandry conditions. Here, we perform lethality tests with two metals, copper chloride and zinc chloride, on five different nematode species, which are nested in their degree of evolutionary relatedness: Caenorhabditis briggsae, Caenorhabditis elegans, Oscheius myriophila, Oscheius tipulae, and Pristionchus pacificus. All species were successfully cultured and tested concurrently with limited resources, demonstrating that inexpensive, multi-species nematode toxicity testing systems are achievable. The results indicate that P. pacificus is most sensitive to both metals. Conversely, C. elegans was the least sensitive species to copper, but the second most sensitive to zinc, indicating that species relationships do not necessarily predict species sensitivity. Toxicity testing with additional nematode species and types of chemicals is feasible and will help form more generalizable conclusions about relative species sensitivity. This article is protected by copyright. All rights reserved.
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[
Evolution,
2006]
The evolution of breeding systems results from the existence of genetic variation and selective forces favoring different outcrossing rates. In this study we determine the extent of genetic variation for characters directly related to outcrossing, such as male frequency, male mating ability, and male reproductive success, in several wild isolates of the nematode Caenorhabditis elegans. This species is characterized by an androdioecious breeding system in which males occur with hermaphrodites that can either self-fertilize or outcross with males. We find genetic variation for all characters measured, but also find that environmental variation is a large fraction of the total phenotypic variance. We further determine the existence of substantial genetic variation for population competitive performance in several laboratory environments. However, these measures are uncorrelated with outcrossing characters. The data presented here contribute to an understanding of male maintenance in natural populations through their role in outcrossing.
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Genetics,
2022]
Over the last 20 years, studies of Caenorhabditis elegans natural diversity have demonstrated the power of quantitative genetic approaches to reveal the evolutionary, ecological, and genetic factors that shape traits. These studies complement the use of the laboratory-adapted strain N2 and enable additional discoveries not possible using only one genetic background. In this chapter, we describe how to perform quantitative genetic studies in Caenorhabditis, with an emphasis on C. elegans. These approaches use correlations between genotype and phenotype across populations of genetically diverse individuals to discover the genetic causes of phenotypic variation. We present methods that use linkage, near-isogenic lines, association, and bulk-segregant mapping, and we describe the advantages and disadvantages of each approach. The power of C. elegans quantitative genetic mapping is best shown in the ability to connect phenotypic differences to specific genes and variants. We will present methods to narrow genomic regions to candidate genes and then tests to identify the gene or variant involved in a quantitative trait. The same features that make C. elegans a preeminent experimental model animal contribute to its exceptional value as a tool to understand natural phenotypic variation.
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[
Heredity,
2010]
Sex determination mechanisms (SDMs) show striking diversity and appear to evolve rapidly. Although interspecific comparisons and studies of ongoing major transitions in sex determination (such as the establishment of new sex chromosomes) have shed light on how SDMs evolve, comparatively little attention has been paid to intraspecific variation with less drastic effects. In this study, I used mutant strains carrying a temperature-sensitive sex determination mutation, along with a second null mutation, in different wild genetic backgrounds to uncover hidden variation in the SDM of the model nematode Caenorhabditis elegans. I then used quantitative trait locus (QTL) mapping to begin to investigate its genetic basis. I identified several QTLs, and although this variation apparently involved genotype-by-temperature interactions, QTL effects were generally consistent across temperatures. These QTLs collectively and individually explained a relatively large fraction of the variance in tail morphology (a sexually dimorphic trait), and two QTLs contained no genes known to be involved in somatic sex determination. These results show the existence of within-species variation in sex determination in this species, and underscore the potential for microevolutionary change in this important developmental pathway.
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Roberto NM, Walhout AJM, Walker M, Kolodziej AR, Na H, Yilmaz LS, Andersen EC, Zhang G, Schroeder FC, Ponomarova O, Crombie TA, Lee YU, Curtis BJ, Fox BW, Giese GE, Rodrigues PR, Zdraljevic S
[
Nature,
2022]
Individuals can exhibit differences in metabolism that are caused by the interplay of genetic background, nutritional input, microbiota and other environmental factors<sup>1-4</sup>. It is difficult to connect differences in metabolism to genomic variation and derive underlying molecular mechanisms in humans, owing to differences in diet and lifestyle, among others. Here we use the nematode Caenorhabditis elegans as a model to study inter-individual variation in metabolism. By comparing three wild strains and the commonly used N2 laboratory strain, we find differences in the abundances of both known metabolites and those that have not to our knowledge been previously described. The latter metabolites include conjugates between 3-hydroxypropionate (3HP) and several amino acids (3HP-AAs), which are much higher in abundance in one of the wild strains. 3HP is an intermediate in the propionate shunt pathway, which is activated when flux through the canonical, vitamin-B<sub>12</sub>-dependent propionate breakdown pathway is perturbed<sup>5</sup>. We show that increased accumulation of 3HP-AAs is caused by genetic variation in HPHD-1, for which 3HP is a substrate. Our results suggest that the production of 3HP-AAs represents a 'shunt-within-a-shunt' pathway to accommodate a reduction-of-function allele in
hphd-1. This study provides a step towards the development of metabolic network models that capture individual-specific differences of metabolism and more closely represent the diversity that is found in entire species.
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Kim H, Shorter J, Jackrel ME, Castellano LM, Jedrzejczak RP, Caldwell KA, Shalem O, Caldwell GA, Willicott CW, Gomes E, Michalska K, March ZM, Lin J, Sweeney K, Yan X, Joachimiak A, Chuang E
[
Elife,
2020]
The AAA+ protein disaggregase, Hsp104, increases fitness under stress by reversing stress-induced protein aggregation. Natural Hsp104 variants might exist with enhanced, selective activity against neurodegenerative disease substrates. However, natural Hsp104 variation remains largely unexplored. Here, we screened a cross-kingdom collection of Hsp104 homologs in yeast proteotoxicity models. Prokaryotic ClpG reduced TDP-43, FUS, and a-synuclein toxicity, whereas prokaryotic ClpB and hyperactive variants were ineffective. We uncovered therapeutic genetic variation among eukaryotic Hsp104 homologs that specifically antagonized TDP-43 condensation and toxicity in yeast and TDP-43 aggregation in human cells. We also uncovered distinct eukaryotic Hsp104 homologs that selectively antagonized a-synuclein condensation and toxicity in yeast and dopaminergic neurodegeneration in <i>C. elegans</i>. Surprisingly, this therapeutic variation did not manifest as enhanced disaggregase activity, but rather as increased passive inhibition of aggregation of specific substrates. By exploring natural tuning of this passive Hsp104 activity, we elucidated enhanced, substrate-specific agents that counter proteotoxicity underlying neurodegeneration.
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[
Nature,
2017]
Genetically identical individuals that grow in the same environment often show substantial phenotypic variation within populations of organisms as diverse as bacteria, nematodes, rodents and humans. With some exceptions, the causes are poorly understood. Here we show that isogenic Caenorhabditis elegans nematodes vary in their size at hatching, speed of development, growth rate, starvation resistance, fecundity, and also in the rate of development of their germline relative to that of somatic tissues. We show that the primary cause of this variation is the age of an individual's mother, with the progeny of young mothers exhibiting several phenotypic impairments. We identify age-dependent changes in the maternal provisioning of the lipoprotein complex vitellogenin to embryos as the molecular mechanism that underlies the variation in multiple traits throughout the life of an animal. The production of sub-optimal progeny by young mothers may reflect a trade-off between the competing fitness traits of a short generation time and the survival and fecundity of the progeny.