Biology subjects

Noble, L. M.

Publications and source records attributed to Noble, L. M..

10 recordsLinked to original sources

bioRxiv2025

Variation in inbreeding depression within and among Caenorhabditis species

Outbreeding populations harbor large numbers of recessive deleterious alleles that reduce the fitness of inbred individuals, and this inbreeding depression potentially shapes the evolution of mating systems, acting as a counterweight to the inherent selective advantage of self-fertilization. The population biological factors that influence inbreeding depression are numerous and often difficult to disentangle. We investigated the utility of obligately-outcrossing (gonochoristic) Caenorhabditis nematodes as models for inbreeding depression. By systematically inbreeding lines from ten populations and tracking line extinction, we found that inbreeding depression is universal but highly variable among species and populations. Inbreeding depression was detected across the life cycle, from mating to embryo production to embryonic viability and larval growth, and reciprocal crosses implicated female-biased effects. In most cases, the surviving inbred lines have dramatically reduced fitness, but the variance among inbred lines is substantial and compatible with the idea that inbreeding depression need not be an obstacle to the evolution of selfing in these worms. Populations of some species, including Caenorhabditis becei, exhibited modest inbreeding depression and could be tractable laboratory models for gonochoristic Caenorhabditis.

evolutionary biology↗

bioRxiv2025

Conservative evolution of genetic and genomic features in Caenorhabditis becei, an experimentally tractable gonochoristic worm

Caenorhabditis nematodes represent a promising model clade for evolutionary genetics and genomics, but research has focused on the three androdioecious species, those with self-fertile hermaphrodites, all in the Elegans Group of species. The majority of Caenorhabditis species are gonochorists, with males and females, characterized by inconveniently high heterozygosity and inbreeding depression. We have identified C. becei as an experimentally tractable gonochorist. We show that transmission-genetic properties known from the androdioecious Elegans Group species are conserved in this Japonica Group species: the organization of the genetic map, cosegregation of autosomal indels and sex chromosomes, and segregation distortion due to Medea elements, demonstrated here for the first time in a gonochoristic Caenorhabditis species. We describe a new chromosomal genome assembly of a healthy inbred C. becei reference strain, integrating data from PacBio HiFi reads, Illumina short reads, genetic linkage, and HiC chromatin contacts, and experimental gene annotation with short- and long-read data. Some aspects of the genome are highly conserved, including synteny across the six chromosomes and the distributions of repetitive sequences and genes along each chromosome. Other features are quite distinctive, including evolved shifts in GC composition & heterogeneity along the genome. Both codon & amino acid usage are shifted in concert with the species' genomic GC content. C. becei has an unusually large X chromosome, which we find is associated with multiple local gene family expansions. These findings and resources lay the foundation for further experimental and computational studies of Caenorhabditis genetics and genomics.

evolutionary biology↗

bioRxiv2023

rec-1 loss of function is insufficient to homogenize crossover distribution in Caenorhabditis elegans

Meiotic control of crossover (CO) position is critical for proper homologous chromosome segregation and organismal fertility, recombination of parental genotypes, and the generation of novel genetic combinations. We here characterize the recombination rate landscape of a loss of function genetic modifier of CO position in Caernorhabditis elegans. By averaging CO position across hermaphrodite and male meioses and by genotyping 203 single-nucleotide variants covering about 95% of the genome, we find that the characteristic chromosomal arm-center recombination rate domain structure is lost in a loss of function rec-1 mutant. The rec-1 loss of function mutant smooths the recombination rate landscape but is insufficient to eliminate the non-uniform position of CO. We further find that the rec-1 mutant is of little consequence for organismal fertility and embryo hatchability and thus for rates of autosomal non-disjunction. However, it specifically increases X chromosome non-disjunction rates and males appearance. Our findings question the maintenance of genetic diversity among C. elegans natural populations, and they further suggest that manipulating genetic modifiers of CO position will help map quantitative trait loci in low-recombining genomic regions.

genetics↗

bioRxiv2022

Caenorhabditis nematodes colonize ephemeral resource patches in neotropical forests.

Factors shaping the distribution and abundance of species include life-history traits, population structure, and stochastic colonization-extinction dynamics. Field studies of model species groups help reveal the roles of these factors. Species of Caenorhabditis nematodes are highly divergent at the sequence level but exhibit highly conserved morphological uniformity, and many of these species live in sympatry on microbe-rich patches of rotten material. Here, we use field experiments and large-scale opportunistic collections to investigate species composition, abundance, and colonization efficiency of Caenorhabditis in two of the worlds best studied lowland tropical field sites: Barro Colorado Island in Panama and La Selva in Sarapiqui, Costa Rica. We observed seven species of Caenorhabditis, four of them known only from these collections. While these localities contain species from many parts of the phylogeny, both localities were dominated by globally distributed androdiecious species. We found that Caenorhabditis were able to colonize baits accessible only by phoresy, preferring to colonize baits making direct contact with the ground. We estimate founder numbers per colonization event to be low.

ecology↗

bioRxiv2020

Selfing is the safest sex for Caenorhabditis tropicalis

Mating systems have profound effects on genetic diversity and compatibility. The convergent evolution of self-fertilization in three Caenorhabditis species provides a powerful lens to examine causes and consequences of mating system transitions. Among the selfers, C. tropicalis is the least genetically diverse and most afflicted by outbreeding depression. We generated a chromosomal-scale genome for C. tropicalis and surveyed global diversity. Population structure is very strong, and islands of extreme divergence punctuate a genomic background that is highly homogeneous around the globe. Outbreeding depression in the laboratory is caused largely by multiple gene drive elements, genetically consistent with maternal toxin/zygotic antidote systems. Driver loci harbor novel and duplicated genes, and their activity is modified by mito-nuclear background. Segregating drivers dramatically reduce fitness, and simulations show that selfing limits their spread. Frequent selfing in C. tropicalis may therefore be a strategy to avoid drive-mediated outbreeding depression.

evolutionary biology↗

bioRxiv2020

The ancestral C. elegans cuticle suppresses rol-1

Genetic background commonly modifies the effects of mutations. We discovered that worms mutant for the canonical rol-1 gene, identified by Brenner in 1974, do not roll in the genetic background of the wild strain CB4856. Using linkage mapping, association analysis and gene editing, we determined that N2 carries an insertion in the collagen gene col-182 that acts as a recessive enhancer of rol-1 rolling. From population and comparative genomics, we infer the insertion is derived in N2 and related laboratory lines, likely arising during the domestication of Caenorhabditis elegans, and breaking a conserved protein. The ancestral version of col-182 also modifies the phenotypes of four other classical cuticle mutant alleles, and the effects of natural genetic variation on worm shape and locomotion. These results underscore the importance of genetic background and the serendipity of Brenners choice of strain.

genetics↗

bioRxiv2019

Gene-level quantitative trait mapping in an expanded C. elegans multiparent experimental evolution panel

The Caenorhabditis elegans multiparental experimental evolution (CeMEE) panel is a collection of genome-sequenced, cryopreserved recombinant inbred lines useful for mapping the genetic basis and evolution of quantitative traits. We have expanded the resource with new lines and new populations, and here report updated additive and epistatic mapping simulations and the genetic and haplotypic composition of CeMEE version 2. Additive QTL explaining 3% of trait variance are detected with >80% power, and the median detection interval is around the length of a single gene on the highly recombinant chromosome arms. Although CeMEE populations are derived from a long-term evolution experiment, genetic structure is dominated by variation present in the ancestral population and is not obviously associated with phenotypic differentiation. C. elegans provides exceptional experimental advantages for the study of phenotypic evolution.

evolutionary biology↗

bioRxiv2019

Cryptic asexual reproduction in Caenorhabditis nematodes revealed by interspecies hybridization

Although most unicellular organisms reproduce asexually, most multicellular eukaryotes are obligately sexual. This implies that there are strong barriers that prevent the origin or maintenance of asexuality arising from an obligately sexual ancestor. By studying rare asexual animal species we can gain a better understanding of the circumstances that facilitate their evolution from a sexual ancestor. Of the known asexual animal species, many originated by hybridization between two ancestral sexual species. The balance hypothesis predicts that genetic incompatibilities between the divergent genomes in hybrids can modify meiosis and facilitate asexual reproduction, but there are few instances where this has been shown. Here we report that hybridizing two sexual Caenorhabditis nematode species (C. nouraguensis females and C. becei males) alters the normal inheritance of the maternal and paternal genomes during the formation of hybrid zygotes. Most offspring of this interspecies cross die during embryogenesis, exhibiting inheritance of a diploid C. nouraguensis maternal genome and incomplete inheritance of C. becei paternal DNA. However, a small fraction of offspring develop into viable adults that can be either fertile or sterile. Fertile offspring are produced asexually by sperm-dependent parthenogenesis (also called gynogenesis or pseudogamy); these progeny inherit a diploid maternal genome but fail to inherit a paternal genome. Sterile offspring are hybrids that inherit both a diploid maternal genome and a haploid paternal genome. Whole-genome sequencing of individual viable worms shows that diploid maternal inheritance in both fertile and sterile offspring results from an altered meiosis in C. nouraguensis oocytes and the inheritance of two randomly selected homologous chromatids. We hypothesize that hybrid incompatibility between C. nouraguensis and C. becei modifies maternal and paternal genome inheritance and indirectly induces gynogenetic reproduction. This system can be used to dissect the molecular mechanisms by which hybrid incompatibilities can facilitate the emergence of asexual reproduction. AUTHOR SUMMARYEukaryotes employ two major reproductive strategies: sexual and asexual reproduction. Both types of reproduction have distinct theoretical costs and benefits, and most unicellular eukaryotes can switch between both modes. However, most multicellular eukaryotes are obligately sexual, implying that there are barriers to the evolution of asexuality from a sexual ancestor. Of the few asexual animal species, many are hybrids of two ancestral sexual species, suggesting that novel genetic interactions in hybrids facilitate the evolution of asexuality. One model suggests that genetic incompatibilities between divergent genomes in hybrids can modify female meiosis and paternal genome inheritance to facilitate asexual reproduction. While studying interspecies hybridizations of Caenorhabditis nematodes, we found that crossing two sexual species (C. nouraguensis and C. becei) disrupts female meiosis and paternal genome inheritance. Most offspring die during embryogenesis, but on rare occasions develop into viable and fertile adults that are produced asexually. This asexual reproduction involves the unusual production of eggs carrying two sets of maternal chromosomes and the loss of the paternal set of chromosomes. We hypothesize that genetic incompatibility between these two species disrupts maternal and paternal genome inheritance. This interspecies hybridization may serve as a model to study how genetic incompatibilities facilitate the emergence of asexuality.

evolutionary biology↗

bioRxiv2018

Comparative genomics of ten new Caenorhabditis species

The nematode Caenorhabditis elegans has been central to the understanding of metazoan biology. However, C. elegans is but one species among millions and the significance of this important model organism will only be fully revealed if it is placed in a rich evolutionary context. Global sampling efforts have led to the discovery of over 50 putative species from the genus Caenorhabditis, many of which await formal species description. Here, we present species descriptions for ten new Caenorhabditis species. We also present draft genome sequences for nine of these new species, along with a transcriptome assembly for one. We exploit these whole-genome data to reconstruct the Caenorhabditis phylogeny and use this phylogenetic tree to dissect the evolution of morphology in the genus. We show unexpected complexity in the evolutionary history of key developmental pathway genes. The genomic data also permit large scale analysis of gene structure, which we find to be highly variable within the genus. These new species and the associated genomic resources will be essential in our attempts to understand the evolutionary origins of the C. elegans model.

evolutionary biology↗

bioRxiv2017

Polygenicity And Epistasis Underlie Fitness-Proximal Traits In The Caenorhabditis elegans Multiparental Experimental Evolution (CeMEE) Panel

Understanding the genetic basis of complex traits remains a major challenge in biology. Polygenicity, phenotypic plasticity and epistasis contribute to phenotypic variance in ways that are rarely clear. This uncertainty is problematic for estimating heritability, for predicting individual phenotypes from genomic data, and for parameterizing models of phenotypic evolution. Here we report a recombinant inbred line (RIL) quantitative trait locus (QTL) mapping panel for the hermaphroditic nematode Caenorhabditis elegans, the C. elegans multiparental experimental evolution (CeMEE) panel. The CeMEE panel, comprising 507 RILs, was created by hybridization of 16 wild isolates, experimental evolution at moderate population sizes and predominant outcrossing for 140-190 generations, and inbreeding by selfing for 13-16 generations. The panel contains 22% of single nucleotide polymorphisms known to segregate in natural populations, and complements existing mapping resources for C. elegans by providing high nucleotide diversity across >95% of the genome. We apply it to study the genetic basis of two fitness components, fertility and hermaphrodite body size at time of reproduction, with high broad sense heritability in the CeMEE. While simulations show we should detect common alleles with additive effects as small as 5%, at gene-level resolution, the genetic architectures of these traits does not feature such alleles. We instead find that a significant fraction of trait variance, particularly for fertility, can be explained by sign epistasis with weak main effects. In congruence, phenotype prediction, while generally poor (r2 < 10%), requires modeling epistasis for optimal accuracy, with most variance attributed to the highly recombinant, rapidly evolving chromosome arms.

evolutionary biology↗