Open AccessThe Relationship between Gene Network Structure and Expression Variation among Individuals and Species
Author(s) -
Karen E. Sears,
Jennifer Maier,
Marcelo RivasAstroza,
Rachel Poe,
Sheng Zhong,
Kari Kosog,
Jonathan D. Marcot,
Richard R. Behringer,
Chris J. Cretekos,
John J. Rasweiler,
Zoi Rapti
Publication year - 2015
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1005398
Subject(s) - biology , limb development , gene , variation (astronomy) , evolutionary biology , gene expression , phenotype , robustness (evolution) , genetics , gene regulatory network , regulation of gene expression , genetic variation , physics , astrophysics
Variation among individuals is a prerequisite of evolution by natural selection. As such, identifying the origins of variation is a fundamental goal of biology. We investigated the link between gene interactions and variation in gene expression among individuals and species using the mammalian limb as a model system. We first built interaction networks for key genes regulating early (outgrowth; E9.5–11) and late (expansion and elongation; E11-13) limb development in mouse. This resulted in an Early (ESN) and Late (LSN) Stage Network. Computational perturbations of these networks suggest that the ESN is more robust. We then quantified levels of the same key genes among mouse individuals and found that they vary less at earlier limb stages and that variation in gene expression is heritable. Finally, we quantified variation in gene expression levels among four mammals with divergent limbs (bat, opossum, mouse and pig) and found that levels vary less among species at earlier limb stages. We also found that variation in gene expression levels among individuals and species are correlated for earlier and later limb development. In conclusion, results are consistent with the robustness of the ESN buffering among-individual variation in gene expression levels early in mammalian limb development, and constraining the evolution of early limb development among mammalian species.