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

Zhang W, Landback P, Gschwend AR, Shen B, Long M - Genome Biol. (2015)

Bottom Line: 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.Our data cast new conceptual insights into the evolution of genetic networks.

View Article: PubMed Central - PubMed

Affiliation: Center for Systems Biology, Soochow University, Suzhou, Jiangsu, 215006, China. wyzhang@uchicago.edu.

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.

No MeSH data available.


Schematic diagram to show the network integration of new genes originating from various phylogenetic branches towards human. a Phylogenetic tree of vertebrates towards human together with branches and divergence times in millions of years from present (myr). The number of genes originating at each phylogenetic branches was also listed. b A sub-graph of human PPI network to show the incorporation of new genes from different originating times
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Fig1: Schematic diagram to show the network integration of new genes originating from various phylogenetic branches towards human. a Phylogenetic tree of vertebrates towards human together with branches and divergence times in millions of years from present (myr). The number of genes originating at each phylogenetic branches was also listed. b A sub-graph of human PPI network to show the incorporation of new genes from different originating times

Mentions: We first analyzed the human protein-protein interactions (hPPIs) network by exploiting and modifying an integrative experimental protein interactions dataset [14] (with the threshold of confidence score of 0.68, see Methods). The reconstructed human PPI network revealed an approximately scale-free topological structure [15] with a degree exponent of 1.49 that defines a power-law distribution of connectivity (or degrees) (Additional file 1: Figure S1 and Additional file 2: Table S1). We then labeled the gene (equivalent to its coded protein) age of each node in the PPI network, determined by an age index for the genes that originated in every period of evolution along the well-resolved phylogeny of vertebrates (Fig. 1a and b), that were retrieved from a widely used database [2, 13] (See Methods). Analysis on the above PPI network indicated a significant and strong correlation (Polynomial regression test, R2 = 0.8834, Fig. 2a) between the ages of genes and their connectivity (or degree, that is, numbers of interacting partners) in the PPI network, revealing a gradual evolutionary process in which new genes are integrated into the PPI network, which echoed the evolutionary procedure of new gene structures [16]. This finding suggests that throughout vertebrate evolution there was a non-robust and rapid process, unexpected by conventional thought, in which new genes were integrated into the GGI networks. During this process of 370 million years (MY, branch 1–12, Fig. 1a) we examined, we observed that 5,710 new genes were integrated into the GGI networks. Furthermore, this process showed an evolutionarily significant pattern: the new genes started, at a young age, to be integrated into networks to form new and less connected branches; however, with the elapse of evolutionary time, as genes grow older, they acquired more interacting links.Fig. 1


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

Zhang W, Landback P, Gschwend AR, Shen B, Long M - Genome Biol. (2015)

Schematic diagram to show the network integration of new genes originating from various phylogenetic branches towards human. a Phylogenetic tree of vertebrates towards human together with branches and divergence times in millions of years from present (myr). The number of genes originating at each phylogenetic branches was also listed. b A sub-graph of human PPI network to show the incorporation of new genes from different originating times
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4590697&req=5

Fig1: Schematic diagram to show the network integration of new genes originating from various phylogenetic branches towards human. a Phylogenetic tree of vertebrates towards human together with branches and divergence times in millions of years from present (myr). The number of genes originating at each phylogenetic branches was also listed. b A sub-graph of human PPI network to show the incorporation of new genes from different originating times
Mentions: We first analyzed the human protein-protein interactions (hPPIs) network by exploiting and modifying an integrative experimental protein interactions dataset [14] (with the threshold of confidence score of 0.68, see Methods). The reconstructed human PPI network revealed an approximately scale-free topological structure [15] with a degree exponent of 1.49 that defines a power-law distribution of connectivity (or degrees) (Additional file 1: Figure S1 and Additional file 2: Table S1). We then labeled the gene (equivalent to its coded protein) age of each node in the PPI network, determined by an age index for the genes that originated in every period of evolution along the well-resolved phylogeny of vertebrates (Fig. 1a and b), that were retrieved from a widely used database [2, 13] (See Methods). Analysis on the above PPI network indicated a significant and strong correlation (Polynomial regression test, R2 = 0.8834, Fig. 2a) between the ages of genes and their connectivity (or degree, that is, numbers of interacting partners) in the PPI network, revealing a gradual evolutionary process in which new genes are integrated into the PPI network, which echoed the evolutionary procedure of new gene structures [16]. This finding suggests that throughout vertebrate evolution there was a non-robust and rapid process, unexpected by conventional thought, in which new genes were integrated into the GGI networks. During this process of 370 million years (MY, branch 1–12, Fig. 1a) we examined, we observed that 5,710 new genes were integrated into the GGI networks. Furthermore, this process showed an evolutionarily significant pattern: the new genes started, at a young age, to be integrated into networks to form new and less connected branches; however, with the elapse of evolutionary time, as genes grow older, they acquired more interacting links.Fig. 1

Bottom Line: 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.Our data cast new conceptual insights into the evolution of genetic networks.

View Article: PubMed Central - PubMed

Affiliation: Center for Systems Biology, Soochow University, Suzhou, Jiangsu, 215006, China. wyzhang@uchicago.edu.

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.

No MeSH data available.