a yeasts eye view of mammalian reproduction cross-species gene co-expression in meiotic prophase哺乳动物生殖跨物种基因的酵母的眼睛看待co-expression在减数分裂前期.pdfVIP

Li et al. BMC Systems Biology 2010, 4:125 /1752-0509/4/125 RESEARCH ARTICLE Open Access A yeast’s eye view of mammalian reproduction: cross-species gene co-expression in meiotic prophase 1,3 1 3 1,2* Yunfei Li , Ka-sum Lam , Nairanjana Dasgupta , Ping Ye Abstract Background: Meiotic prophase is a critical stage in sexual reproduction. Aberrant chromosome recombination during this stage is a leading cause of human miscarriages and birth defects. However, due to the experimental intractability of mammalian gonads, only a very limited number of meiotic genes have been characterized. Here we aim to identify novel meiotic genes important in human reproduction through computational mining of cross- species and cross-sex time-series expression data from budding yeast, mouse postnatal testis, mouse embryonic ovary, and human fetal ovary. Results: Orthologous gene pairs were ranked by order statistics according to their co-expression profiles across species, allowing us to infer conserved meiotic genes despite obvious differences in cellular synchronicity and composition in organisms. We demonstrated that conserved co-expression networks could successfully recover known meiotic genes, including homologous recombination genes, chromatin cohesion genes, and genes regulating meiotic entry. We also showed that conserved co-expression pairs exhibit functional connections, as evidenced by the annotation similarity in Gene Ontology and overlap with physical interactions. More importantly, we predicted six new meiotic genes through their co-expression linkages with known meiotic genes, and subsequently used the genetically more amenable yeast system for experimental validation. The deletion mutants of all six genes showed sporulation defects, equivalent to a 100% v