Salomon MP et al. (2009) Genetics "Comparing mutational and standing genetic variability for fitness and size in Caenorhabditis briggsae and C. elegans."

Bour W, Phillips N, Baer CF, Salomon MP, Ostrow D, Sylvestre T, Upadhyay A, Keller TE, Blanton D, Levy L

[Genetics, 2009]

The genetic variation present in a species depends on the interplay between mutation, population size, and natural selection. At mutation-(purifying) selection balance (MSB) in a large population, the standing genetic variance for a trait (VG) is predicted to be proportional to the mutational variance for the trait (VM); VM is proportional to the mutation rate for the trait. The ratio VM/VG predicts the average strength of selection (S) against a new mutation. Here we compare VM and VG for lifetime reproductive success (approximately fitness) and body volume in two species of self-fertilizing rhabditid nematodes, Caenorhabditis briggsae and C. elegans, which the evidence suggests have different mutation rates. Averaged over traits, species, and populations within species, the relationship between VG and VM is quite stable, consistent with the hypothesis that differences among groups in standing variance can be explained by differences in mutational input. The average (homozygous) selection coefficient inferred from VM/VG is a few percent, smaller than typical direct estimates from mutation accumulation (MA) experiments. With one exception, the variance present in a worldwide sample of these species is similar to the variance present within a sample from a single locale. These results are consistent with specieswide MSB and uniform purifying selection, but genetic draft (hitchhiking) is a plausible alternative possibility.

Chen JS et al. (1997) J Mol Evol "Extensive sequence conservation among insect, nematode, and vertebrate vitellogenins reveals ancient common ancestry."

Chen JS, Raikhel AS, Sappington TW

[J Mol Evol, 1997]

The eggs of most oviparous animals are provisioned with a class of protein called vitellogenin (Vg) which is stored as the major component of yolk. Until recently, deduced amino acid sequences were available only from vertebrate and nematode Vgs, which proved to be homologous. The sequences of several insect Vgs are now known, but early attempts at pairwise alignments with vertebrate and nematode Vgs have been problematic, leading to conflicting conclusions about how closely insect Vgs are related to the others. In this paper we demonstrate that insect VE sequences can be confidently aligned with one another along their entire lengths and with multiple vertebrate and nematode Vg sequences along most of their spans. Although divergence is high, conservation among insect, vertebrate, and nematode Vg sequences is widespread with a preponderance of glycine, proline, and cysteine residues among strictly conserved amino acids, establishing conclusively that Vgs from the three phyla are homologous. Areas of least-certain alignment are primarily in and around insect and vertebrate polyserine domains which are not homologous. Phylogenetic reconstructions of Vgs based on sequence identities indicate that the insect lineage is the most diverged and that the mammalian serum protein, apolipoprotein B-100, arose from a Vg ancestor after the nematode/vertebrate divergence.

Farhadifar R et al. (2016) Genetics "Mutation Is a Sufficient and Robust Predictor of Genetic Variation for Mitotic Spindle Traits in Caenorhabditis elegans."

Andersen EC, Ponciano JM, Baer CF, Needleman DJ, Farhadifar R

[Genetics, 2016]

Different types of phenotypic traits consistently exhibit different levels of genetic variation in natural populations. There are two potential explanations: either mutation produces genetic variation at different rates, or natural selection removes or promotes genetic variation at different rates. Whether mutation or selection is of greater general importance is a longstanding unresolved question in evolutionary genetics. We report mutational variances (VM) for 19 traits related to the first mitotic cell division in C. elegans, and compare them to the standing genetic variances (VG) for the same suite of traits in a worldwide collection C. elegans Two robust conclusions emerge. First, the mutational process is highly repeatable: the correlation between VM in two independent sets of mutation accumulation lines is ~0.9. Second, VM for a trait is a good predictor of VG for that trait: the correlation between VM and VG is ~0.9. This result is predicted for a population at mutation-selection balance; it is not predicted if balancing selection plays a primary role in maintaining genetic variation.

Farhadifar, Reza et al. (2015) International Worm Meeting "Mutation is a sufficient predictor of genetic variation for mitotic spindle traits in C. elegans."

Ponciano, Jose Miguel, Farhadifar, Reza, Andersen, Erik, Needleman, Daniel, Baer, Charles

[International Worm Meeting, 2015]

Seemingly similar phenotypic traits can vary considerably in the extent of genetic variation in the trait. If two traits in the same set of organisms have different levels of genetic variation, there are two potential underlying causes: mutation and/or selection. Traits may differ in the mutational target they present, or in the rate at which those loci mutate. Traits may also differ in the average effect that mutations have on the trait. Alternatively, selection may differ between traits.We investigated these issues by comparing the input of genetic variation by mutation to the standing genetic variation found in a worldwide collection of C. elegans for a suite of 19 traits related to the first mitotic cell division. The results are striking: the mutational variance (VM) explains 90% of the variation in the standing genetic variance (VG). One of the traits - embryo length - has been previously shown to be under stabilizing selection. The strong positive relationship between VM and VG remains after accounting for variation in embryo length. Mutations were allowed to accumulate in two separate experiments in two different genetic backgrounds (N2 and PB306). The correlation between VM in the two experiments was ~0.9, which indicates that for a given set of traits, the mutational process produces highly repeatable outcomes.The ratio of VG/VM can be interpreted as the number of generations of mutation required to produce that amount of variation in the population. For 18 of the 19 traits (embryo length notwithstanding) the ratio of VG/VM is on the order of a few hundred generations. That result is consistent with molecular evidence suggesting that C. elegans has recently undergone a species-wide selective sweep that purged most of the standing genetic variation.We conclude that variation among traits in the amount of genetic variation in the population is a predictable function of the mutational input, and that the role of direct and/or linked natural selection is secondary. This result has implications for understanding the genetic architecture of complex traits in any organism, including humans.

Salomon, Matthew et al. (2009) International Worm Meeting "Persistence time of mutations affecting fitness and body size in Caenorhabditis briggsae and C. elegans."

Upadhyay, Ambuj, Salomon, Matthew, Baer, Charles, Levy, Laura, Keller, Thomas, Phillips, Naomi, Blanton, Dustin, Ostrow, Dejerianne, Bour, Whitney, Sylvestre, Thamar

[International Worm Meeting, 2009]

The level of genetic variation present in a population is a composite function of mutation, population size, and natural selection. Historically, efforts to understand differences (or similarities) between groups in levels of genetic variation have focused on the interplay between population size and natural selection. However, much less attention has been paid to the alternative possibility that differences among groups are due to systematic differences in the underlying rate of mutation. Much of the difficulty in interpreting the role of mutation stems from the fact that most of what is known about genomic mutational properties, for quantitative traits in multicellular eukaryotes, comes from a handful of phylogenetically distant and biologically dissimilar model organisms, making meaningful comparisons difficult. Over the past several years our lab has been investigating the properties of new mutations in a model nematode system within a comparative phylogenetic framework. Mutations have been allowed to accumulate in the (relative) absence of natural selection, thus allowing us to estimate the genetic variance introduced by new mutation (VM) for two species of rhabditid nematodes, Caenorhabditis elegans and C. briggsae. Previous work in this system suggests that the mutation rate in C. briggsae is on the order of twice that of C. elegans for quantitative traits and dinucleotide repeats. Here we report the standing genetic variance (VG) for two quantitative traits, lifetime reproduction and body size, in worldwide collections of C. briggsae and C. elegans natural isolates. Comparisons of VG to VM between the natural isolates and our mutation accumulation lines allow us to infer the magnitude and pattern of constraint on phenotypic evolution in these two species. Taking the results from the two species together, the persistence time (VG/VM) of new mutations affecting fitness is on the order of tens to perhaps hundreds of generations, with an average selection coefficient against homozygotes of a few per-cent. Furthermore, the pattern of persistence time for mutations affecting adult body size is onsistent with that of fitness in both species. These results suggest that idiosyncratic selection, perhaps due to random hitchhiking - "genetic draft" - is paramount in shaping the standing genetic variance of these traits in these species.

Rodriguez-Perez MA et al. (2010) Am J Trop Med Hyg "Interruption of transmission of Onchocerca volvulus in the Oaxaca focus, Mexico."

Orozco-Algarra ME, Rodriguez-Perez MA, Morales-Castro AL, Dominguez-Vazquez A, Rendon VG, Pena-Flores GP, Arredondo-Jimenez JI, Vasquez-Rodriguez MA, Unnasch TR, Richards F

[Am J Trop Med Hyg, 2010]

All endemic communities of the Oaxaca focus of onchocerciasis in southern Mexico have been treated annually or semi-annually with ivermectin since 1994. In-depth epidemiologic assessments were performed in communities during 2007 and 2008. None of the 52,632 Simulium ochraceum s.l. collected in four sentinel communities was found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the infection rate in the vectors of 0.07/2,000. The prevalence of microfilariae (mf) in the cornea and/or anterior chamber of the eye was also zero (0 of 1,039 residents examined; 95%-UL = 0.35%). Similarly, all 1,164 individuals examined by skin biopsy were mf negative (95%-UL = 0.31%), and sera collected from 3,569 children from 25 communities did not harbor Ov16 IgG4-antibodies (95%-UL = 0.09%). These meet the criteria for absence of morbidity and parasite transmission in the Oaxaca focus. As a result mass treatments with ivermectin were halted in 2009.

Etienne V et al. (2015) Evolution "The red death meets the abdominal bristle: polygenic mutation for susceptibility to a bacterial pathogen in Caenorhabditis elegans."

Blanton D, Ponciano JM, Cadavid A, Joyner-Matos J, Baer CF, Andersen EC, Matsuba C, Etienne V, Tabman B

[Evolution, 2015]

Understanding the genetic basis of susceptibility to pathogens is an important goal of medicine and of evolutionary biology. A key first step toward understanding the genetics and evolution of any phenotypic trait is characterizing the role of mutation. However, the rate at which mutation introduces genetic variance for pathogen susceptibility in any organism is essentially unknown. Here, we quantify the per-generation input of genetic variance by mutation (VM) for susceptibility of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa (defined as the median time of death, LT50). VM for LT50 is slightly less than VM for a variety of life-history and morphological traits in this strain of C. elegans, but is well within the range of reported values in a variety of organisms. Mean LT50 did not change significantly over 250 generations of mutation accumulation. Comparison of VM to the standing genetic variance (VG) implies a strength of selection against new mutations of a few tenths of a percent. These results suggest that the substantial standing genetic variation for susceptibility of C. elegans to P. aeruginosa can be explained by polygenic mutation coupled with purifying selection.

Matthew Salomon et al. (2007) International Worm Meeting "Persistence time of mutations affecting fitness and body size in C. elegans and C. briggsae."

Matthew Salomon, Jasmine Brown, Charles Baer, Dejerianne Ostrow, Charlie Shaw

[International Worm Meeting, 2007]

For traits closely tied to fitness, most mutations are deleterious and the ratio t of the standing genetic variance (VG) to the per-generation input of genetic variance from new mutations (VM) provides a measure of the time that a mutation persists in the population and of the strength of selection on mutant alleles. Previous experiments have shown that the deleterious mutation rate in C. elegans is lower than that of Drosophila melanogaster, but how much lower is unresolved. For mutations affecting viability in Drosophila, t ~100 generations. We present data on standing and mutational genetic variance for total fitness and body size in C. elegans. For fitness, t~20 generations, very consistent with the Drosophila results when mating system is taken into account. Preliminary data from C. briggsae suggest that t for fitness is very similar to C. elegans, consistent with an approximately two-fold higher mutation rate in C. briggsae. The difference in mating system between flies and C. elegans suggests that natural selection may have favored a reduction of the mutation rate in the self-compatible taxon, as predicted by theory.

Vecseri G et al. (1991) International C. elegans Meeting "AN UNUSUAL MUTANT STRAIN OF CAENORAHBDITIS BRIGGSAE (G16)."

Buza J, Fodor A, Vecseri G

[International C. elegans Meeting, 1991]

The founder animal of strain vg-182 was isolated as a Large Roller progeny of an EMS treated C. briggsae (G16) hermaphrodite. It has segregated only a few offsprings including Lons and animals of variable phenotypes. Lon hermaphrodites were singled and self-fertilized through subsequent generations and then crossed out several times. During this process 7 of 8 fertile lines segregated Lon males, Large Dpy hermaphrodites, Small Dumpies and Large Rollers. At the end, loci represented by one X-linked dominant lon, one autosomal recessive dpy and one independent, autosomal squat allele, respectively, could be identified and named temporarily as lon-2, dpy- 2 and sqt-l. lon-2(d) proved a dominant epistatic gene over dpy-2 and a semidominant epistatic one over sqt-l. (Worms of sqt-l; +/+; lon-2 genotype exhibited Large Roller phenotype while those of sqt-l/+; lon- 2/0 genotype were large, Non-Roller males.) The male--segregating (Him) phenotype could not be separated from lon-2(d). The lon-2 hermaphrodites kept in liquid nitrogene still keep their 'him' phenotype, those which were kept in laboratory conditions lost their male-segregating ability. The possibilities of getting a mutator strain of C. briggsae are discussed.

Braendle, Christian et al. (2009) International Worm Meeting "Quantifying the robustness and evolvability of a developmental system."

Felix, Marie-Anne, Braendle, Christian, Baer, Charles F

[International Worm Meeting, 2009]

Many developmental processes generate invariant phenotypes despite environmental or mutational perturbations. Such robustness is a fundamental biological property, yet its extent, limits and adaptive significance have rarely been assessed empirically. Here we tested how environmental variation and accumulation of spontaneous random mutation impact the developmental system underlying vulval formation in Caenorhabditis nematodes. In different environments, a correct vulval pattern develops with high precision but rare deviant patterns reveal the system''s limits and how its mechanisms respond to environmental challenges. Key features of the apparent robustness are functional redundancy among vulval precursor cells and tolerance to quantitative variation in Ras, Notch and Wnt pathway activities. These environmental responses and the precision of the vulval patterning process further vary within and between Caenorhabditis species. To quantify how developmental precision responds to mutational perturbations, we used a set of mutation accumulation (MA) lines derived from two C. briggsae and two C. elegans genotypes. Developmental defects and variants increased after MA treatment for all tested genotypes, yet the type and proportion of the mutationally induced variation varied among genotypes. Thus, the mutability of this developmental system evolves, so that the mutationally induced phenotypic space is biased depending on the genetic background. Comparison of the standing genetic variance (VG) for deviant vulva phenotypes with the mutational variance (VM) leads to the conclusion that strong natural selection acts to maintain the robustness of this developmental process.