title: New genes drive the evolution of gene interaction networks in the human and mouse genomes.
abstract: BACKGROUND
  The origin of new genes with novel functions creates genetic and phenotypic diversity in organisms. To acquire functional roles, new genes must integrate into ancestral gene-gene interaction (GGI) networks. The mechanisms by which new genes are integrated into ancestral networks, and their evolutionary significance, are yet to be characterized. Herein, we present a study investigating the rates and patterns of new gene-driven evolution of GGI networks in the human and mouse genomes.
  
  
  RESULTS
  We examine the network topological and functional evolution of new genes that originated at various stages in the human and mouse lineages by constructing and analyzing three different GGI datasets. We find a large number of new genes integrated into GGI networks throughout vertebrate evolution. These genes experienced a gradual integration process into GGI networks, starting on the network periphery and gradually becoming highly connected hubs, and acquiring pleiotropic and essential functions. We identify a few human lineage-specific hub genes that have evolved brain development-related functions. Finally, we explore the possible underlying mechanisms driving the GGI network evolution and the observed patterns of new gene integration process.
  
  
  CONCLUSIONS
  Our results unveil a remarkable network topological integration process of new genes: over 5000 new genes were integrated into the ancestral GGI networks of human and mouse; new genes gradually acquire increasing number of gene partners; some human-specific genes evolved into hub structure with critical phenotypic effects. Our data cast new conceptual insights into the evolution of genetic networks.
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, Jiangsu, 215006, China. wyzhang@uchicago.edu.|Department of Ecology and Evolution, The University of Chicago, Chicago, IL, 60637, USA. wyzhang@uchicago.edu.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Committee on Genetics, The University of Chicago, Chicago, IL, 60637, USA. landback@uchicago.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Landback
authors.affiliation: Department of Ecology and Evolution, The University of Chicago, Chicago, IL, 60637, USA. agschwend@uchicago.edu.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Gschwend
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, Jiangsu, 215006, China. bairong.shen@suda.edu.cn.|Department of Bioinformatics, Medical College, Soochow University, Suzhou, Jiangsu, 215123, China. bairong.shen@suda.edu.cn.
authors.forename: Bairong
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Ecology and Evolution, The University of Chicago, Chicago, IL, 60637, USA. mlong@uchicago.edu.|Committee on Genetics, The University of Chicago, Chicago, IL, 60637, USA. mlong@uchicago.edu.
authors.forename: Manyuan
authors.initials: M
authors.lastname: Long
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks; D016678:Genome; D015894:Genome, Human; D006801:Humans; D051379:Mice