New genes drive the evolution of gene interaction networks in the human and mouse genomes

Abstract

BackgroundThe 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0772-4) contains supplementary material, which is available to authorized users.

What Signatures Dominantly Associate with Gene Age?

“…It has been reported that more than one-third of known regulatory interactions in yeast (Teichmann and Babu 2004) and average 27% interaction networks for primate-specific young genes in human (Zhang et al 2015) are inherited from their parental genes after duplication, so that duplication is a significant contributor of gene interaction network (Middendorf et al 2005). In contrast to duplicates that have inherited PPIN from parental copies, singletons have little interactions at their early evolutionary stage, but, over time, they are gradually integrated into gene interaction networks to acquire biological functions.…”

“…S6, Supplementary Material online). Consequently, even though old genes (including duplicates and singletons) tend to be highly connected in PPIN (Zhang et al 2015), PPIN appears to be a more important signature of evolutionary age in singletons. Taken together, GC content and PPIN are two dominant signatures in close association with gene age, yet exhibiting heterogeneity in duplicates and singletons and presumably reflecting complex differential interplays between natural selection and mutation as they age.…”

“…These studies revealed that young genes are shorter, have fewer introns (Wolf et al 2009), relate closely with the birth of new binding sites (Ni et al 2012) and harbor more premature termination codon mutations (Yang et al 2015). Furthermore, young genes possess fewer interactions with other genes (Zhang et al 2015) and tend to play less essential functional roles compared with old genes (Chen et al 2012). Additionally, young human genes are likely to present distinct temporal and spatial expression patterns (Long et al 2013; Popadin et al 2014).…”

AspWood: High-Spatial-Resolution Transcriptome Profiles Reveal Uncharacterized Modularity of Wood Formation in Populus tremula

“…Notably, several of the de novo identified protein coding and lincRNA genes were highly central in the coexpression network (Supplemental Data Set 7), indicating that they may serve important functional roles in cambial growth and wood formation in aspen. However, compared with previously annotated genes, a higher proportion of novel genes were not integrated into the network (;30% versus ;50%), which might reflect their evolutionary recent origin (i.e., low conservation; Supplemental Data Set 7), as suggested by Zhang et al (2015), or reflect weaker genetic control over their expression. Such genes represent potential species-or clade-specific adaptations and regulatory mechanisms.…”

Designing Graphical Data Storage Model for Gene-Protein and Gene-Gene Interaction Networks

“…Ancestral networks mechanisms of human and mouse genomes that are characterized by the new gene integration, and gene evolutionary significance are discussed in [51]. Exploration of their generation frequencies and patterns of new gene-driven evolution of Gene Gene Interaction networks is also discussed.…”