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.
[
International C. elegans Meeting,
2001]
To build upon knowledge gained from the genome of C. elegans , we have begun generating Expressed Sequence Tags (ESTs) from parasitic (and free-living) nematodes. This project will generate >225,000 5' ESTs from 14 species by 2003. Additionally, the Sanger Centre and Edinburgh Univ. will complete 80,000 ESTs from 7 species. Through these combined efforts, we anticipate the identification of >80,000 new nematode genes. At the GSC, approximately 35,000 ESTs have been generated to date including sequences from Ancylostoma caninum, Heterodera glycines, Meloidogyne incognita and javanica, Parastrongyloides trichosuri, Pristionchus pacificus, Strongyloides stercoralis and ratti, Trichinella spiralis, and Zeldia punctata . We will report on our progress in sequence analysis, including the creation of the NemaGene gene index for each species by EST clustering and consensus sequence generation, identification of common and rare transcripts, and identification of genes with orthologues in C. elegans and other nematodes. All sequences are publicly available at www.ncbi.nlm.nih.gov/dbEST. NemaGene sequences and project details are available at WWW.NEMATODE.NET. We would like to thank collaborators who have provided materials and ideas for this project including Prema Arasu, David Bird, Rick Davis, Warwick Grant, John Hawdon, Doug Jasmer, Andrew Kloek, Thomas Nutman, Charlie Opperman, Alan Scott, Ralf Sommer, and Mark Viney. This work is funded by NIH-AI-46593, NSF-0077503, and a Merck / Helen Hay Whitney Foundation fellowship.
[
International C. elegans Meeting,
2001]
Two web sites have been established to allow easier access to nematode sequences from species other than C. elegans and C. briggsae ; WWW.NEMATODE.NET is maintained by the Genome Sequencing Center (GSC) at Washington University in collaboration with North Carolina State University, and WWW.NEMATODES.ORG is maintained by Mark Blaxter's lab at the University of Edinburgh. Useful features being built for NEMATODE.NET include the following - 1) Searches: All nematode expressed sequence tags (ESTs) generated at the GSC, currently 32,000 from 10 species, and NemaGene clusters built from these ESTs, are available for BLAST and text searching. Searches can be directed by species, library, or nematode clade in a way that is not possible using the NCBI EST database dbEST. 2) FTP: All EST project data can be downloaded for local analysis including FASTA files and sequence trace image files. 3) Trace Viewer: Fluorescent trace representations for each EST can be viewed. Traces can sometimes provide additional sequence information not included in the EST due to quality value cut-offs. 4) Project Updates: Information is available about libraries in construction and sequencing in progress as the project expands toward 235,000 ESTs. 5) Clone Requests: Details on clone availability and ordering procedure are provided. 6) Links: The site includes an up-to-date set of 300 links to information on human, animal, and plant parasitic nematodes. Further plans for NEMATODE.NET include linking of ESTs to their closest C. elegans homologues by DAS third-party curation of Wormbase. This work is funded by NIH-AI-46593, NSF-0077503, and a Merck / Helen Hay Whitney Foundation fellowship.