title: Evolutionary and Topological Properties of Genes and Community Structures in Human Gene Regulatory Networks.
abstract: The diverse, specialized genes present in today's lifeforms evolved from a common core of ancient, elementary genes. However, these genes did not evolve individually: gene expression is controlled by a complex network of interactions, and alterations in one gene may drive reciprocal changes in its proteins' binding partners. Like many complex networks, these gene regulatory networks (GRNs) are composed of communities, or clusters of genes with relatively high connectivity. A deep understanding of the relationship between the evolutionary history of single genes and the topological properties of the underlying GRN is integral to evolutionary genetics. Here, we show that the topological properties of an acute myeloid leukemia GRN and a general human GRN are strongly coupled with its genes' evolutionary properties. Slowly evolving ("cold"), old genes tend to interact with each other, as do rapidly evolving ("hot"), young genes. This naturally causes genes to segregate into community structures with relatively homogeneous evolutionary histories. We argue that gene duplication placed old, cold genes and communities at the center of the networks, and young, hot genes and communities at the periphery. We demonstrate this with single-node centrality measures and two new measures of efficiency, the set efficiency and the interset efficiency. We conclude that these methods for studying the relationships between a GRN's community structures and its genes' evolutionary properties provide new perspectives for understanding evolutionary genetics.
authors.affiliation: Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Szedlak
authors.affiliation: Salgomed Inc., Del Mar, California, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Smith
authors.affiliation: College of Health Solutions, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paternostro
authors.affiliation: Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Carlo
authors.initials: C
authors.lastname: Piermarocchi
mesh_terms: D019295:Computational Biology; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008957:Models, Genetic