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[
Genetics,
2019]
Hybrid male progeny from interspecies crosses are more prone to sterility or inviability than hybrid female progeny, and the male sterility and inviability often demonstrate parent-of-origin asymmetry. However, the underlying genetic mechanism of asymmetric sterility or inviability remains elusive. We previously established a genome-wide hybrid incompatibility (HI) landscape between Caenorhabditis briggsae and C. nigoni by phenotyping a large collection of C. nigoni strains each carrying a C. briggsae introgression. In this study, we systematically dissect the genetic mechanism of asymmetric sterility and inviability in both hybrid male and female progeny between the two species. Specifically, we performed reciprocal crosses between C. briggsae and different C. nigoni strains that each carry a GFP-labeled C. briggsae genomic fragment referred to as introgression, and scored the HI phenotypes in the F1 progeny. The aggregated introgressions cover 94.6% of the C. briggsae genome, including 100% of the X chromosome. Surprisingly, we observed that two C. briggsaeX fragments that produce C. nigoni male sterility as an introgression rescued hybrid F1 sterility in males fathered by C. briggsae Subsequent backcrossing analyses indicated that a specific interaction between the X-linked interaction and one autosome introgression is required to rescue the hybrid male sterility. In addition, we identified another two C. briggsae genomic intervals on chromosomes II and IV that can rescue the inviability, but not the sterility, of hybrid F1 males fathered by C. nigoni, suggesting the involvement of differential epistatic interactions in the asymmetric hybrid male fertility and inviability. Importantly, backcrossing of the rescued sterile males with C. nigoni led to the isolation of a 1.1-Mb genomic interval that specifically interacts with an X-linked introgression, which is essential for hybrid male fertility. We further identified three C. briggsae genomic intervals on chromosome I, II, and III that produced inviability in all F1 progeny, dependent on or independent of the parent-of-origin. Taken together, we identified multiple independent interacting loci that are responsible for asymmetric hybrid male and female sterility, and inviability, which lays a foundation for their molecular characterization.
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[
PLoS Genet,
2015]
Systematic characterization of ybrid incompatibility (HI) between related species remains the key to understanding speciation. The genetic basis of HI has been intensively studied in Drosophila species, but remains largely unknown in other species, including nematodes, which is mainly due to the lack of a sister species with which C. elegans can mate and produce viable progeny. The recent discovery of a C. briggsae sister species, C. nigoni, has opened up the possibility of dissecting the genetic basis of HI in nematode species. However, the paucity of dominant and visible marker prevents the efficient mapping of HI loci between the two species. To elucidate the genetic basis of speciation in nematode species, we first generated 96 chromosomally integrated GFP markers in the C. briggsae genome and mapped them into the defined locations by PCR and Next-Generation Sequencing (NGS). Aided by the marker, we backcrossed the GFP-associated C. briggsae genomic fragments into C. nigoni for at least 15 generations and produced 111 independent introgressions. The introgression fragments cover most of the C. briggsae genome. We finally dissected the patterns of HI by scoring the embryonic lethality, larval arrest, sex ratio and male sterility for each introgression line, through which we identified pervasive HI loci and produced a genome-wide landscape of HI between the two nematode species, the first of its type for any non-Drosophila species. The HI data not only provided insights into the genetic basis of speciation, but also established a framework for the possible cloning of HI loci between the two nematode species. Furthermore, the data on hybrids confirmed Haldane's rule and suggested the presence of a large X effect in terms of fertility between the two species. Importantly, this work opens a new avenue for studying speciation genetics between nematode species and allows parallel comparison of the HI with that in Drosophila and other species.
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[
International Worm Meeting,
2017]
Hybrid incompatibility (HI) between related species plays a key role in speciation. The genetic basis of HI has been intensively studied in yeast, Drosophila, and mouse species, but remains largely unexplored in nematodes until recent isolation of a C. briggsae sister species, C. nigoni, which can mate with each other and produce a few viable progeny. We have recently generated a genome-wide HI map between the two species by phenotyping 111 hybrid strains, each carrying a defined introgression fragment derived from GFP-labeled C. briggsae chromosome. Notably, the HI phenotypes were scored essentially in the C. nigoni background produced by GFP-aided backcrossing for at least 15 generations. However, many HI phenotypes were manifested in the F1 generation, often in a crossing direction-dependent manner. Unfortunately, few HI loci have been mapped in F1 hybrid between the two species. We address this issue using the large collection of introgression strains. This is because the crossings between individual C. nigoni strains carrying a defined C. briggsae fragment and C. briggsae wild isolate AF16 will produce selective homozygosity or hemizygosity of the C. briggsae genomic fragment in the F1 hybrid, whereas the remaining genomic contents would be comparable to those of the F1 hybrids between the wild isolates of the two species. Contrasting the hybrid F1 phenotypes in the crossings of AF16 with C. nigoni wild isolate or with an introgression strain permits isolation of HI loci in the F1 generation. We perform the crossings in both directions between AF16 and the introgression strains that are prioritized based on the even distribution of introgressions over the C. briggsae genome. Altogether, the introgression fragments cover approximately 80% of the C. briggsae genome. Surprisingly, we identified numerous C. briggsae loci that produced an opposite HI phenotype in F1 hybrid compared to that in the introgression lines, including rescue of male sterility and killing of female, which is consistent with the BDM model of speciation. In addition, some autosomal HI loci demonstrate crossing direction-dependent HI phenotypes, for example, selective male killing or global killing of all progeny, while others show crossing direction-independent killing of all progeny. In summary, we are able to identify numerous C. briggsae loci that produce crossing direction-dependent or independent incompatible phenotypes in F1 hybrids, which provide a foundation for molecular characterization of HI between the two nematodes.
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[
Mol Biol Evol,
2007]
The Y genes encode small non-coding RNAs whose functions remain elusive, whose numbers vary between species, and whose major property is to be bound by the Ro60 protein (or its ortholog in other species). To better understand the evolution of the Y gene family, we performed a homology search in 27 different genomes along with a structural search using Y RNA specific motifs. These searches confirmed that Y RNAs are well conserved in the animal kingdom and resulted in the detection of several new Y RNA genes, including the first Y RNAs in insects and a second Y RNA detected in Caenorhabditis elegans. Unexpectedly, Y5 genes were retrieved almost as frequently as Y1 and Y3 genes, and, consequently are not the result of a relatively recent apparition as is generally believed. Investigation of the organization of the Y genes demonstrated that the synteny was conserved among species. Interestingly, it revealed the presence of six putative "fossil" Y genes, all of which were Y4 and Y5 related. Sequence analysis led to inference of the ancestral sequences for all Y RNAs. In addition, the evolution of existing Y RNAs was deduced for many families, orders and classes. Moreover, a consensus sequence and secondary structure for each Y species was determined. Further evolutionary insight was obtained from the analysis of several thousand Y retropseudogenes among various species. Taken together, these results confirm the rich and diversified evolution history of Y RNAs.
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[
Biogerontology,
2013]
Lactobacilli and bifidobacteria are probiotic bacteria that modify host defense systems and have the ability to extend the lifespan of the nematode Caenorhabditis elegans. Here, we attempted to elucidate the mechanism by which bifidobacteria prolong the lifespan of C. elegans. When the nematode was fed Bifidobacterium infantis (BI) mixed at various ratios with the standard food bacterium Escherichia coli strain OP50 (OP), the mean lifespan of worms was extended in a dose-dependent manner. Worms fed BI displayed higher locomotion and produced more offspring than control worms. The growth curves of nematodes were similar regardless of the amount of BI mixed with OP, suggesting that BI did not induce prolongevity effects through caloric restriction. Notably, feeding worms the cell wall fraction of BI alone was sufficient to promote prolongevity. The accumulation of protein carbonyls and lipofuscin, a biochemical marker of aging, was also lower in worms fed BI; however, the worms displayed similar susceptibility to heat, hydrogen peroxide, and paraquat, an inducer of free radicals, as the control worms. As a result of BI feeding, loss-of-function mutants of
daf-16,
jnk-1,
aak-2,
tol-1, and
tir-1 exhibited a longer lifespan than OP-fed control worms, but BI failed to extend the lifespan of
pmk-1,
skn-1, and
vhp-1 mutants. As
skn-1 induces phase 2 detoxification enzymes, our findings suggest that cell wall components of bifidobacteria increase the average lifespan of C. elegans via activation of
skn-1, regulated by the
p38 MAPK pathway, but not by general activation of the host defense system via DAF-16.
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[
Biochim Biophys Acta,
2016]
BothDrosophila melanogaster and Caenorhabditis elegans (C. elegans) are useful model organisms to study in vivo roles of NF-Y during development. Drosophila NF-Y (dNF-Y) consists of three subunits dNF-YA, dNF-YB and dNF-YC. In some tissues, dNF-YC-related protein Mes4 may replace dNF-YC in dNF-Y complex. Studies with eye imaginal disc-specific dNF-Y-knockdown flies revealed that dNF-Y positively regulates the sevenless gene encoding a receptor tyrosine kinase, a component of the ERK pathway and negatively regulates the Sensless gene encoding a transcription factor to ensure proper development of R7 photoreceptor cells together with proper R7 axon targeting. dNF-Y also controls the Drosophila Bcl-2 (debcl) to regulate apoptosis. In thorax development, dNF-Y is necessary for both proper Drosophila JNK (basket) expression and JNK signaling activity that is responsible for thorax development. Drosophila
p53 gene was also identified as one of the dNF-Y target genes in this system. C. elegans contains two forms of NF-YA subunit, CeNF-YA1 and CeNF-YA2. C. elegans NF-Y (CeNF-Y) therefore consists of CeNF-YB, CeNF-YC and either CeNF-YA1 or CeNF-YA2. CeNF-Y negatively regulates expression of the Hox gene
egl-5 (ortholog of Drosophila Abdominal-B) that is involved in tail patterning. CeNF-Y also negatively regulates expression of the
tbx-2 gene that is essential for development of the pharyngeal muscles, specification of neural cell fate and adaptation in olfactory neurons. Negative regulation of the expression of
egl-5 and
tbx-2 by CeNF-Y provides new insight into the physiological meaning of negative regulation of gene expression by NF-Y during development. In addition, studies on NF-Y in platyhelminths are also summarized.
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[
Toxicol Appl Pharmacol,
2023]
Different classes of insecticide compounds have been employed to control insects and mosquitoes; Pyrethroids are one of the most common used in both urban and rural household environments. This study investigated the effects of exposure of two doses of commercial transfluthrin-based insecticide (T-BI) on behavior (body bends, pharyngeal pumping rate, and feeding attributes) and biochemical biomarkers (AChE, PolyQ40 aggregations, HSP, antioxidative SOD, CTL, and GST) following three different protocols (transgenerational, neonatal, and lifespan) in Caenorhabditis elegans model system. The relative calculated dose (RCD) and relative calculated half dose (RCHD) of T-BI were compared with those of the control (water). T-BI reduced the health span of worms treated during their whole life and changed biochemical and behavioral patterns due to progenitors' uterine (transgenerational) and neonatal exposures. It was inferred that the effects of T-BI are transgenerational and persistent and can be harmful to non-target species, including humans. In addition, our findings highlight that T-BI contact by progenitors accelerates the establishment of Huntington's disease and causes a cholinergic outbreak in offspring adulthood.
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[
Trends in Cell Biology,
1996]
Keeling and Logsdon propose that the y-like sequences from Caenorhabditis elegans and Saccharomyces cerevisiae are bona fide y-tubulins that have undergone rapid evolutionary divergence. Indeed, genetic and localization studies with the yeast epsilon-tubulin (encoded by the TUB4 gene) reveal striking similarities to the bona fide y-tubulins, whereas there is no apparent human analogue to the C. elegans delta-tubulin among the 60 available human y-tubulin expressed-sequence tags. (ESTs).
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[
RNA,
2009]
Noncoding Y RNAs are required for the reconstitution of chromosomal DNA replication in late G1 phase template nuclei in a human cell-free system. Y RNA genes are present in all vertebrates and in some isolated nonvertebrates, but the conservation of Y RNA function and key determinants for its function are unknown. Here, we identify a determinant of Y RNA function in DNA replication, which is conserved throughout vertebrate evolution. Vertebrate Y RNAs are able to reconstitute chromosomal DNA replication in the human cell-free DNA replication system, but nonvertebrate Y RNAs are not. A conserved nucleotide sequence motif in the double-stranded stem of vertebrate Y RNAs correlates with Y RNA function. A functional screen of human Y1 RNA mutants identified this conserved motif as an essential determinant for reconstituting DNA replication in vitro. Double-stranded RNA oligonucleotides comprising this RNA motif are sufficient to reconstitute DNA replication, but corresponding DNA or random sequence RNA oligonucleotides are not. In intact cells, wild-type hY1 or the conserved RNA duplex can rescue an inhibition of DNA replication after RNA interference against hY3 RNA. Therefore, we have identified a new RNA motif that is conserved in vertebrate Y RNA evolution, and essential and sufficient for Y RNA function in human chromosomal DNA replication.
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[
J Bacteriol,
2006]
Yersinia pestis, the agent of plague, is usually transmitted by fleas. To produce a transmissible infection, Y. pestis colonizes the flea midgut and forms a biofilm in the proventricular valve, which blocks normal blood feeding. The enteropathogen Yersinia pseudotuberculosis, from which Y. pestis recently evolved, is not transmitted by fleas. However, both Y. pestis and Y. pseudotuberculosis form biofilms that adhere to the external mouthparts and block feeding of Caenorhabditis elegans nematodes, which has been proposed as a model of Y. pestis-flea interactions. We compared the ability of Y. pestis and Y. pseudotuberculosis to infect the rat flea Xenopsylla cheopis and to produce biofilms in the flea and in vitro. Five of 18 Y. pseudotuberculosis strains, encompassing seven serotypes, including all three serotype O3 strains tested, were unable to stably colonize the flea midgut. The other strains persisted in the flea midgut for 4 weeks but did not increase in numbers, and none of the 18 strains colonized the proventriculus or produced a biofilm in the flea. Y. pseudotuberculosis strains also varied greatly in their ability to produce biofilms in vitro, but there was no correlation between biofilm phenotype in vitro or on the surface of C. elegans and the ability to colonize or block fleas. Our results support a model in which a genetic change in the Y. pseudotuberculosis progenitor of Y. pestis extended its pre-existing ex vivo biofilm-forming ability to the flea gut environment, thus enabling proventricular blockage and efficient flea-borne transmission.