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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

Fraction of topologically and functionally essential genes for gene groups from different divergence times. a Fraction of hub genes in PPI network within gene groups of different divergence times. Hub genes are defined as genes with network connectivity greater than median level (Interaction degree > = 6). Branch assignment is labeled near each data point. The age assignment for each branch follows Fig. 1. The dash line indicates the polynomial regression correlation between divergence times of genes and the fractions of hub genes. b Fraction of essential genes in regards to their PPI network connectivity. The solid line indicates the linear regression correlation between PPI network connectivity of genes and the fractions of essential genes within each gene group. c Fraction of essential genes in PPI network within gene groups from different divergence times. The dash line indicates the polynomial regression correlation between divergence times of genes and the fractions of essential genes
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Fig6: Fraction of topologically and functionally essential genes for gene groups from different divergence times. a Fraction of hub genes in PPI network within gene groups of different divergence times. Hub genes are defined as genes with network connectivity greater than median level (Interaction degree > = 6). Branch assignment is labeled near each data point. The age assignment for each branch follows Fig. 1. The dash line indicates the polynomial regression correlation between divergence times of genes and the fractions of hub genes. b Fraction of essential genes in regards to their PPI network connectivity. The solid line indicates the linear regression correlation between PPI network connectivity of genes and the fractions of essential genes within each gene group. c Fraction of essential genes in PPI network within gene groups from different divergence times. The dash line indicates the polynomial regression correlation between divergence times of genes and the fractions of essential genes

Mentions: One critical feature of scale-free networks is the existence of hub nodes, or highly connected nodes [24]. Hub nodes are essential components in various networks [25], and are subjected to concentrated evolutionary forces that shape the network structures to result in essential functions [3, 26]. To explore the contribution of new genes in reshaping the GGI network, we investigated the percentage distributions of hub genes (with interaction degrees no smaller than 6) originating across different phylogenetic branches in human PPI network. The data revealed a strong correlation between gene ages and fractions of hub genes (Polynomial regression correlation test, R2 = 0.8016, Fig. 6a). In particular, we found a high proportion of hub genes (16 %) arising in the most recently originated human-specific branch (Branch 12, Fig. 1a), and this number gradually increased with gene ages, peaking at around 53 % for the earliest originating genes (Branch 0, genes arising before the split of vertebrates, Fig. 1a). This phenomenon indicates the gradual process of new genes evolving to be network hubs, and reshaping the original gene interaction networks.Fig. 6


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)

Fraction of topologically and functionally essential genes for gene groups from different divergence times. a Fraction of hub genes in PPI network within gene groups of different divergence times. Hub genes are defined as genes with network connectivity greater than median level (Interaction degree > = 6). Branch assignment is labeled near each data point. The age assignment for each branch follows Fig. 1. The dash line indicates the polynomial regression correlation between divergence times of genes and the fractions of hub genes. b Fraction of essential genes in regards to their PPI network connectivity. The solid line indicates the linear regression correlation between PPI network connectivity of genes and the fractions of essential genes within each gene group. c Fraction of essential genes in PPI network within gene groups from different divergence times. The dash line indicates the polynomial regression correlation between divergence times of genes and the fractions of essential genes
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4590697&req=5

Fig6: Fraction of topologically and functionally essential genes for gene groups from different divergence times. a Fraction of hub genes in PPI network within gene groups of different divergence times. Hub genes are defined as genes with network connectivity greater than median level (Interaction degree > = 6). Branch assignment is labeled near each data point. The age assignment for each branch follows Fig. 1. The dash line indicates the polynomial regression correlation between divergence times of genes and the fractions of hub genes. b Fraction of essential genes in regards to their PPI network connectivity. The solid line indicates the linear regression correlation between PPI network connectivity of genes and the fractions of essential genes within each gene group. c Fraction of essential genes in PPI network within gene groups from different divergence times. The dash line indicates the polynomial regression correlation between divergence times of genes and the fractions of essential genes
Mentions: One critical feature of scale-free networks is the existence of hub nodes, or highly connected nodes [24]. Hub nodes are essential components in various networks [25], and are subjected to concentrated evolutionary forces that shape the network structures to result in essential functions [3, 26]. To explore the contribution of new genes in reshaping the GGI network, we investigated the percentage distributions of hub genes (with interaction degrees no smaller than 6) originating across different phylogenetic branches in human PPI network. The data revealed a strong correlation between gene ages and fractions of hub genes (Polynomial regression correlation test, R2 = 0.8016, Fig. 6a). In particular, we found a high proportion of hub genes (16 %) arising in the most recently originated human-specific branch (Branch 12, Fig. 1a), and this number gradually increased with gene ages, peaking at around 53 % for the earliest originating genes (Branch 0, genes arising before the split of vertebrates, Fig. 1a). This phenomenon indicates the gradual process of new genes evolving to be network hubs, and reshaping the original gene interaction networks.Fig. 6

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