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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.


Related in: MedlinePlus

Average rate of evolving linking partners (interactions / myr) for genes from different phylogenetic branches based on the human PPI network (a) and mouse PPI network (b). The dash line indicates the power regression correlation between evolution rates of interactions for genes and their divergence times. Numbers near each data point are phylogenetic branch assignments for each group of genes. The divergence time of each gene age group is assigned as the middle time point for each branch. And the oldest branch (branch 0) is arbitrarily set as 500 myr
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Fig3: Average rate of evolving linking partners (interactions / myr) for genes from different phylogenetic branches based on the human PPI network (a) and mouse PPI network (b). The dash line indicates the power regression correlation between evolution rates of interactions for genes and their divergence times. Numbers near each data point are phylogenetic branch assignments for each group of genes. The divergence time of each gene age group is assigned as the middle time point for each branch. And the oldest branch (branch 0) is arbitrarily set as 500 myr

Mentions: Given the observation that the acquisition of genetic interactions is a time-dependent gradual procedure, we further investigated whether this process occurred at a constant rate. Our result showed that new genes could establish linking partners at a high rate (interactions acquired per million years) in the initial stage of their origination. After that, the rate dramatically declined, and finally plateaued (Fig. 3a and b), suggesting that the acquisition of biological roles of new genes is a rapid process during early evolution, but as the genes age, the function spectrum is diversified at a much lower rate. Taking advantage of the high coverage of the human PPI data (Additional file 2: Table S1), we subsequently focused on the analysis of both topological and functional evolution patterns of new genes based on our first constructed human PPI network.Fig. 3


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)

Average rate of evolving linking partners (interactions / myr) for genes from different phylogenetic branches based on the human PPI network (a) and mouse PPI network (b). The dash line indicates the power regression correlation between evolution rates of interactions for genes and their divergence times. Numbers near each data point are phylogenetic branch assignments for each group of genes. The divergence time of each gene age group is assigned as the middle time point for each branch. And the oldest branch (branch 0) is arbitrarily set as 500 myr
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Average rate of evolving linking partners (interactions / myr) for genes from different phylogenetic branches based on the human PPI network (a) and mouse PPI network (b). The dash line indicates the power regression correlation between evolution rates of interactions for genes and their divergence times. Numbers near each data point are phylogenetic branch assignments for each group of genes. The divergence time of each gene age group is assigned as the middle time point for each branch. And the oldest branch (branch 0) is arbitrarily set as 500 myr
Mentions: Given the observation that the acquisition of genetic interactions is a time-dependent gradual procedure, we further investigated whether this process occurred at a constant rate. Our result showed that new genes could establish linking partners at a high rate (interactions acquired per million years) in the initial stage of their origination. After that, the rate dramatically declined, and finally plateaued (Fig. 3a and b), suggesting that the acquisition of biological roles of new genes is a rapid process during early evolution, but as the genes age, the function spectrum is diversified at a much lower rate. Taking advantage of the high coverage of the human PPI data (Additional file 2: Table S1), we subsequently focused on the analysis of both topological and functional evolution patterns of new genes based on our first constructed human PPI network.Fig. 3

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.


Related in: MedlinePlus