Constraint and divergence of global gene expression in the mammalian embryo

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Abstract

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 (ASE) 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.

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Noah Spies

Deaprtment of Pathology and Genetics, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Cheryl L Smith

Department of Genetics and Pathology, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Jesse M Rodriguez

Google Inc., Mountain View, United States

Competing interests
The authors declare that no competing interests exist.
Julie C Baker

Department of Genetics, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Serafim Batzoglou

Department of Computer Science, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Arend Sidow

Department of Pathology, Stanford University School of Medicine, Stanford, United States

For correspondence
arend@stanford.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experimental procedures were carried out in accordance with the Administrative Panel on Laboratory Animal Care protocols (#11799 and #13646) and the institutional guidelines set by the Veterinary Service Center at Stanford University.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.