TY - JOUR
T1 - The Relationship between Gene Network Structure and Expression Variation among Individuals and Species
AU - Sears, Karen E.
AU - Maier, Jennifer A.
AU - Rivas-Astroza, Marcelo
AU - Poe, Rachel
AU - Zhong, Sheng
AU - Kosog, Kari
AU - Marcot, Jonathan D.
AU - Behringer, Richard R.
AU - Cretekos, Chris J.
AU - Rasweiler, John J.
AU - Rapti, Zoi
N1 - Publisher Copyright:
© 2015 Sears et al.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84940749611&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1005398
DO - 10.1371/journal.pgen.1005398
M3 - Article
C2 - 26317994
AN - SCOPUS:84940749611
VL - 11
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 8
M1 - e1005398
ER -