title: The Relationship between Gene Network Structure and Expression Variation among Individuals and Species.
abstract: 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.
authors: School of Integrative Biology, University of Illinois, Urbana, Illinois, United States of America; Institute for Genomic Biology, University of Illinois, Urbana, Illinois, United States of America.
authors: Karen E
authors: KE
authors: Sears
authors: School of Integrative Biology, University of Illinois, Urbana, Illinois, United States of America.
authors: Jennifer A
authors: JA
authors: Maier
authors: Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America.
authors: Marcelo
authors: M
authors: Rivas-Astroza
authors: Department of Mathematics, University of Illinois, Urbana, Illinois, United States of America.
authors: Rachel
authors: R
authors: Poe
authors: Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America.
authors: Sheng
authors: S
authors: Zhong
authors: School of Integrative Biology, University of Illinois, Urbana, Illinois, United States of America.
authors: Kari
authors: K
authors: Kosog
authors: School of Integrative Biology, University of Illinois, Urbana, Illinois, United States of America.
authors: Jonathan D
authors: JD
authors: Marcot
authors: Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Richard R
authors: RR
authors: Behringer
authors: Department of Biological Sciences, Idaho State University, Pocatello, Idaho, United States of America.
authors: Chris J
authors: CJ
authors: Cretekos
authors: Department of Obstetrics and Gynecology, State University of New York Downstate Medical Center, Brooklyn, New York, United States of America.
authors: John J
authors: JJ
authors: Rasweiler
authors: Department of Mathematics, University of Illinois, Urbana, Illinois, United States of America.
authors: Zoi
authors: Z
authors: Rapti
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002685:Chiroptera / Q000235:genetics; D003198:Computer Simulation; D005121:Extremities / Q000196:embryology* / Q000254:growth & development; D015870:Gene Expression / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D018878:Limb Buds / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D051379:Mice; D009893:Opossums / Q000235:genetics; D012641:Selection, Genetic; D013552:Swine / Q000235:genetics