Redes de genes orientam um curso para a evolução antes da natureza selecionar

sexta-feira, setembro 04, 2015

The Relationship between Gene Network Structure and Expression Variation among Individuals and Species

Karen E. Sears , Jennifer A. Maier, Marcelo Rivas-Astroza, Rachel Poe, Sheng Zhong, Kari Kosog, Jonathan D. Marcot, Richard R. Behringer, Chris J. Cretekos†, John J. Rasweiler IV, Zoi Rapti

Published: August 28, 2015DOI: 10.1371/journal.pgen.1005398

Courtesy of/Cortesia de Karen Sears


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.

Author Summary

The variation generating mechanisms of development interact with the variation sorting mechanism of natural selection to produce organismal diversity. While the impacts of natural selection on existing variation have received much study, those of development on the generation of this variation remain less understood. This fundamental gap in our knowledge restricts our understanding of the key processes shaping evolution. In this study, we combine mathematical modeling, and population-level and cross-species assays of gene expression to investigate the relationship between the structure of the gene interactions regulating limb development and variation in the expression of limb genes among individuals and species. Results suggest that the way in which genes interact (i.e., development) biases the distribution of variation in gene expression among individuals, and that this in turn biases the distribution of variation among species.

Citation: Sears KE, Maier JA, Rivas-Astroza M, Poe R, Zhong S, Kosog K, et al. (2015) The Relationship between Gene Network Structure and Expression Variation among Individuals and Species. PLoS Genet 11(8): e1005398. doi:10.1371/journal.pgen.1005398

Editor: Artyom Kopp, University of California Davis, UNITED STATES

Received: January 20, 2015; Accepted: June 27, 2015; Published: August 28, 2015

Copyright: © 2015 Sears et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All data files are available in the Gene Expression Omnibus (GEO) under accession number GSE71390.

Funding: This research was funded by National Science Foundation grants to KES (1257873), RRB (1256423), CJC (1255926), and ZR (1129198). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.