whole genome sequencing highlights genetic changes associated with laboratory domestication of c. elegans全基因组测序亮点与实验室驯化的秀丽隐杆线虫相关基因变化.pdf

Whole Genome Sequencing Highlights Genetic Changes Associated with Laboratory Domestication of C. elegans 1 1 2 2 1 Katherine P. Weber , Subhajyoti De , Iwanka Kozarewa , Daniel J. Turner , M. Madan Babu , Mario de Bono1* 1 Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom, 2 Wellcome Trust Sanger Institute, Hinxton, United Kingdom Abstract Defining the mutational landscape when individuals of a species grow separately and diverge over many generations can provide insights into trait evolution. A specific example of this involves studying changes associated with domestication where different lines of the same wild stock have been cultivated independently in different standard environments. Whole genome sequence comparison of such lines permits estimation of mutation rates, inference of genes’ ancestral states and ancestry of existing strains, and correction of sequencing errors in genome databases. Here we study domestication of the C. elegans Bristol strain as a model, and report the genome sequence of LSJ1 (Bristol), a sibling of the standard C. elegans reference wild type N2 (Bristol). The LSJ1 and N2 lines were cultivated separately from shortly after the Bristol strain was isolated until methods to freeze C. elegans were developed. We find that during this time the two strains have accumulated 1208 genetic differences. We describe phenotypic variation between N2 and LSJ1 in the rate at which embryos develop, the rate of production of eggs, the maturity of eggs at laying, and feeding behavior, all the result of post-isolation changes. We infer the ancestral alleles in the original Bristol isolate and highlight 2038 likely sequencing errors in the original N2 reference genome sequence. Ma