Constraint and divergence of global gene expression in the mammalian embryo
Noah Spies,
Cheryl L Smith,
Jesse M Rodriguez,
Julie C Baker,
Serafim Batzoglou,
Arend Sidow
Affiliations
Noah Spies
Department of Pathology, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Cheryl L Smith
Department of Pathology, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Jesse M Rodriguez
Department of Computer Science, Stanford University, Stanford, United States; Biomedical Informatics Program, Stanford University School of Medicine, Stanford, United States
Julie C Baker
Department of Genetics, Stanford University School of Medicine, Stanford, United States
Serafim Batzoglou
Department of Computer Science, Stanford University, Stanford, United States
Arend Sidow
Department of Pathology, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
The effects of genetic variation on gene regulation in the developing mammalian embryo remain largely unexplored. To globally quantify these effects, we crossed two divergent mouse strains and asked how genotype of the mother or of the embryo drives gene expression phenotype genomewide. Embryonic expression of 331 genes depends on the genotype of the mother. Embryonic genotype controls allele-specific expression of 1594 genes and a highly overlapping set of cis-expression quantitative trait loci (eQTL). A marked paucity of trans-eQTL suggests that the widespread expression differences do not propagate through the embryonic gene regulatory network. The cis-eQTL genes exhibit lower-than-average evolutionary conservation and are depleted for developmental regulators, consistent with purifying selection acting on expression phenotype of pattern formation genes. The widespread effect of maternal and embryonic genotype in conjunction with the purifying selection we uncovered suggests that embryogenesis is an important and understudied reservoir of phenotypic variation.
