Mammalian meiosis is more conserved by sex than by species: conserved co-expression networks of meiotic prophase

Abstract

Despite the importance of meiosis to human reproduction, we know remarkably little about the genes and pathways that regulate meiotic progression through prophase in any mammalian species. Microarray expression profiles of mammalian gonads provide a valuable resource for probing gene networks. However, expression studies are confounded by mixed germ cell and somatic cell populations in the gonad and asynchronous germ cell populations. Further, widely used clustering methods for analyzing microarray profiles are unable to prioritize candidate genes for testing. To derive a comprehensive understanding of gene expression in mammalian meiotic prophase, we constructed conserved co-expression networks by linking expression profiles of male and female gonads across mouse and human. We demonstrate that conserved gene co-expression dramatically improved the accuracy of detecting known meiotic genes compared with using co-expression in individual studies. Interestingly, our results indicate that meiotic prophase is more conserved by sex than by species. The co-expression networks allowed us to identify genes involved in meiotic recombination, chromatin cohesion, and piRNA metabolism. Further, we were able to prioritize candidate genes based on quantitative co-expression links with known meiotic genes. Literature studies of these candidate genes suggest that some are human disease genes while others are associated with mammalian gonads. In conclusion, our co-expression networks provide a systematic understanding of cross-sex and cross-species conservations observed during meiotic prophase. This approach further allows us to prioritize candidate meiotic genes for in-depth mechanistic studies in the future.