Genomic diversity landscapes in outcrossing and selfing Caenorhabditis nematodes.

Caenorhabditis nematodes form an excellent model for studying how the mode of reproduction affects genetic diversity, as some species reproduce via outcrossing whereas others can self-fertilize. Currently, chromosome-level patterns of diversity and recombination are only available for self-reproducing Caenorhabditis, making the generality of genomic patterns across the genus unclear given the profound potential influence of reproductive mode. Here we present a whole-genome diversity landscape, coupled with a new genetic map, for the outcrossing nematode C.

A polygenic two-hit hypothesis for prostate cancer.

Prostate cancer is one of the most heritable cancers. Hundreds of germline polymorphisms have been linked to prostate cancer diagnosis and prognosis. Polygenic risk scores can predict genetic risk of a prostate cancer diagnosis.

Ephemeral-habitat colonization and neotropical species richness of Caenorhabditis nematodes.

Background: The drivers of species co-existence in local communities are especially enigmatic for assemblages of morphologically cryptic species. Here we characterize the colonization dynamics and abundance of nine species of Caenorhabditis nematodes in neotropical French Guiana, the most speciose known assemblage of this genus, with resource use overlap and notoriously similar external morphology despite deep genomic divergence.

Methods: To characterize the dynamics and specificity of colonization and exploitation of ephemeral resource patches, we conducted manipulative field experiments and the largest sampling effort to date for Caenorhabditis outside of Europe.

Hitting two birds with one stone: The unforeseen consequences of nested gene knockouts in Caenorhabditis elegans.

Nested genes represent an intriguing form of non-random genomic organization in which the boundaries of one gene are fully contained within another, longer host gene. The C. elegans genome contains over 10,000 nested genes, 92% of which are ncRNAs, which occur inside 16% of the protein coding gene complement.

Comparative genomic analysis of upstream miRNA regulatory motifs in Caenorhabditis.

MicroRNAs (miRNAs) comprise a class of short noncoding RNA molecules that play diverse developmental and physiological roles by controlling mRNA abundance and protein output of the vast majority of transcripts. Despite the importance of miRNAs in regulating gene function, we still lack a complete understanding of how miRNAs themselves are transcriptionally regulated. To fill this gap, we predicted regulatory sequences by searching for abundant short motifs located upstream of miRNAs in eight species of Caenorhabditis nematodes.

When natural selection gives gene function the cold shoulder.

It is tempting to invoke organismal selection as perpetually optimizing the function of any given gene. However, natural selection can drive genic functional change without improvement of biochemical activity, even to the extinction of gene activity. Detrimental mutations can creep in owing to linkage with other selectively favored loci.

No Evidence that MicroRNAs Coevolve with Genes Located in Copy Number Regions.

MicroRNAs (miRNAs) are a widespread class of regulatory noncoding RNAs with key roles in physiology and development, conferring robustness to noise in regulatory networks. Consistent with this buffering function, it was recently suggested that human miRNAs coevolve with genes in copy number regions (copy number variation [CNV] genes) to reduce dosage imbalance. Here, I compare miRNA regulation between CNV and non-CNV genes in four model organisms.

Full-genome evolutionary histories of selfing, splitting, and selection in Caenorhabditis.

The nematode Caenorhabditis briggsae is a model for comparative developmental evolution with C. elegans. Worldwide collections of C.

Microevolution of nematode miRNAs reveals diverse modes of selection.

Micro-RNA (miRNA) genes encode abundant small regulatory RNAs that play key roles during development and in homeostasis by fine tuning and buffering gene expression. This layer of regulatory control over transcriptional networks is preserved by selection across deep evolutionary time, yet selection pressures on individual miRNA genes in contemporary populations remain poorly characterized in any organism. Here, we quantify nucleotide variability for 129 miRNAs in the genome of the nematode Caenorhabditis remanei to understand the microevolution of this important class of regulatory genes.

A recent global selective sweep on the age-1 phosphatidylinositol 3-OH kinase regulator of the insulin-like signaling pathway within Caenorhabditis remanei.

The discovery that genetic pathways can be manipulated to extend lifespan has revolutionized our understanding of aging, yet their function within natural populations remains poorly characterized. In particular, evolutionary theories of aging predict tradeoffs in resource investment toward somatic maintenance vs. reproductive output that should impose strong natural selection on genetic components that influence this balance.

Specialist versus generalist life histories and nucleotide diversity in Caenorhabditis nematodes.

Species with broad ecological amplitudes with respect to a key focal resource, niche generalists, should maintain larger and more connected populations than niche specialists, leading to the prediction that nucleotide diversity will be lower and more subdivided in specialists relative to their generalist relatives. This logic describes the specialist-generalist variation hypothesis (SGVH). Some outbreeding species of Caenorhabditis nematodes use a variety of invertebrate dispersal vectors and have high molecular diversity.

Outbreeding depression with low genetic variation in selfing Caenorhabditis nematodes.

Theory and empirical study produce clear links between mating system evolution and inbreeding depression. The connections between mating systems and outbreeding depression, whereby fitness is reduced in crosses of less related individuals, however, are less well defined. Here we investigate inbreeding and outbreeding depression in self-fertile androdioecious nematodes, focusing on Caenorhabditis sp.

Pleiotropic constraints, expression level, and the evolution of miRNA sequences.

Post-transcriptional gene regulation mediated by microRNAs (miRNAs) plays critical roles during development by modulating gene expression and conferring robustness to stochastic errors. Phylogenetic analyses suggest that miRNA acquisition could play a role in phenotypic innovation. Moreover, miRNA-induced regulation strongly impacts genome evolution, increasing selective constraints on 3'UTRs, protein sequences, and expression level divergence.

Fine-scale signatures of molecular evolution reconcile models of indel-associated mutation.

Genomic structural alterations that vary within species, known as large copy number variants, represent an unanticipated and abundant source of genetic diversity that associates with variation in gene expression and susceptibility to disease. Even short insertions and deletions (indels) can exert important effects on genomes by locally increasing the mutation rate, with multiple mechanisms proposed to account for this pattern. To better understand how indels promote genome evolution, we demonstrate that the single nucleotide mutation rate is elevated in the vicinity of indels, with a resolution of tens of base pairs, for the two closely related nematode species Caenorhabditis remanei and C.

Molecular hyperdiversity and evolution in very large populations.

The genomic density of sequence polymorphisms critically affects the sensitivity of inferences about ongoing sequence evolution, function and demographic history. Most animal and plant genomes have relatively low densities of polymorphisms, but some species are hyperdiverse with neutral nucleotide heterozygosity exceeding 5%. Eukaryotes with extremely large populations, mimicking bacterial and viral populations, present novel opportunities for studying molecular evolution in sexually reproducing taxa with complex development.

Species richness, distribution and genetic diversity of Caenorhabditis nematodes in a remote tropical rainforest.

Background: In stark contrast to the wealth of detail about C. elegans developmental biology and molecular genetics, biologists lack basic data for understanding the abundance and distribution of Caenorhabditis species in natural areas that are unperturbed by human influence.

Methods: Here we report the analysis of dense sampling from a small, remote site in the Amazonian rain forest of the Nouragues Natural Reserve in French Guiana.

MicroRNA sequence variation potentially contributes to within-species functional divergence in the nematode Caenorhabditis briggsae.

Mounting evidence points to differences in gene regulation as a major source of phenotypic variation. MicroRNA-mediated post-transcriptional regulation has emerged recently as a key factor controlling gene activity during development. MicroRNA genes are abundant in genomes, acting as managers of gene expression by directing translational repression.

Expression level drives the pattern of selective constraints along the insulin/Tor signal transduction pathway in Caenorhabditis.

Genes do not act in isolation but perform their biological functions within genetic pathways that are connected in larger networks. Investigation of nucleotide variation within genetic pathways and networks has shown that topology can affect the rate of protein evolution; however, it remains unclear whether a same pattern of nucleotide variation is expected within functionally similar networks and whether it may be due to similar or different biological mechanisms. We address these questions by investigating nucleotide variation in the context of the structure of the insulin/Tor-signaling pathway in Caenorhabditis, which is well characterized and is functionally conserved across phylogeny.

Rapid sequence evolution of transcription factors controlling neuron differentiation in Caenorhabditis.

Whether phenotypic evolution proceeds predominantly through changes in regulatory sequences is a controversial issue in evolutionary genetics. Ample evidence indicates that the evolution of gene regulatory networks via changes in cis-regulatory sequences is an important determinant of phenotypic diversity. However, recent experimental work suggests that the role of transcription factor (TF) divergence in developmental evolution may be underestimated.

Evolution of developmental regulation in the vertebrate FgfD subfamily.

Fibroblast growth factors (Fgfs) encode small signaling proteins that help regulate embryo patterning. Fgfs fall into seven families, including FgfD. Nonvertebrate chordates have a single FgfD gene; mammals have three (Fgf8, Fgf17, and Fgf18); and teleosts have six (fgf8a, fgf8b, fgf17, fgf18a, fgf18b, and fgf24).

Evolutionary rates and centrality in the yeast gene regulatory network.

Background: Transcription factors play a fundamental role in regulating physiological responses and developmental processes. Here we examine the evolution of the yeast transcription factors in the context of the structure of the gene regulatory network.

Results: In contrast to previous results for the protein-protein interaction and metabolic networks, we find that the position of a gene within the transcription network affects the rate of protein evolution such that more central transcription factors tend to evolve faster.

High nucleotide divergence in developmental regulatory genes contrasts with the structural elements of olfactory pathways in caenorhabditis.

Almost all organismal function is controlled by pathways composed of interacting genetic components. The relationship between pathway structure and the evolution of individual pathway components is not completely understood. For the nematode Caenorhabditis elegans, chemosensory pathways regulate critical aspects of an individual's life history and development.

Duplication and divergence of fgf8 functions in teleost development and evolution.

Fibroblast growth factors play critical roles in many aspects of embryo patterning that are conserved across broad phylogenetic distances. To help understand the evolution of fibroblast growth factor functions, we identified members of the Fgf8/17/18-subfamily in the three-spine stickleback Gasterosteus aculeatus, and investigated their evolutionary relationships and expression patterns. We found that fgf17b is the ortholog of tetrapod Fgf17, whereas the teleost genes called fgf8 and fgf17a are duplicates of the tetrapod gene Fgf8, and thus should be called fgf8a and fgf8b.

Functional constraint and divergence in the G protein family in Caenorhabditis elegans and Caenorhabditis briggsae.

Part of the challenge of the post-genomic world is to identify functional elements within the wide array of information generated by genome sequencing. Although cross-species comparisons and investigation of rates of sequence divergence are an efficient approach, the relationship between sequence divergence and functional conservation is not clear. Here, we use a comparative approach to examine questions of evolutionary rates and conserved function within the guanine nucleotide-binding protein (G protein) gene family in nematodes of the genus Caenorhabditis.