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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.


Human lineage-specific hub genes and their first-level linking partners. This figure illustrates two fetus brain biased human lineage-specific hub genes (top) and two unbiased human lineage-specific hub genes (bottom) and their direct interacting partners from the human PPI network. Genes biased in fetus brain (blue), adult brain (red), and unbiased (orange) between fetus and adult brain are marked. Genes (in square circles) outlined in the green dashed rectangle have been reported to have some brain development-related functions in previous literature
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Fig8: Human lineage-specific hub genes and their first-level linking partners. This figure illustrates two fetus brain biased human lineage-specific hub genes (top) and two unbiased human lineage-specific hub genes (bottom) and their direct interacting partners from the human PPI network. Genes biased in fetus brain (blue), adult brain (red), and unbiased (orange) between fetus and adult brain are marked. Genes (in square circles) outlined in the green dashed rectangle have been reported to have some brain development-related functions in previous literature

Mentions: More intriguingly, four human-lineage specific (the genes that originated only in the human lineage since its divergence and thus exist only in the human genome) hub genes with clear expression evidence in human brain were found (Additional file 8: Table S4). As there was no direct clue in literatures about their functions in brain development of these four genes, we conducted a ‘guilt by connection’ study to investigate the reported evidence for the roles in brain function of their direct linking partners by manual curation of early studies (Additional file 9: Table S5). For instance, CCT4, a subunit of chaperonin containing TCP1, was reported to be involved with development of a brain malfunction disorder - Alzheimer’s disease [33], and it was also shown that CCT4 (gene id: 10575) is a direct interacting partner of one of young hub gene - FAM86B2 (gene id: 653333, Fig. 8). Collectively, we found that 62.5 % (10 of 16) and 53.3 % (8 of 15) of the first-layer linking partners for two out of the four hub genes, which were fetus brain biased, were confirmed to be involved in brain development (Fig. 8 and Additional file 9: Table S5). While for the other two unbiased hub genes, 24.4 % (10 out of 41) and 50 % (3 out of 6) were proven to function in brain development in previous literature (Fig. 8 and Additional file 9: Table S5). As genes with similar functions tend to be within the same network cluster [34], this evidence suggests these four human-lineage specific hub genes could also be with associated functions in human brain development.Fig. 8


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)

Human lineage-specific hub genes and their first-level linking partners. This figure illustrates two fetus brain biased human lineage-specific hub genes (top) and two unbiased human lineage-specific hub genes (bottom) and their direct interacting partners from the human PPI network. Genes biased in fetus brain (blue), adult brain (red), and unbiased (orange) between fetus and adult brain are marked. Genes (in square circles) outlined in the green dashed rectangle have been reported to have some brain development-related functions in previous literature
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig8: Human lineage-specific hub genes and their first-level linking partners. This figure illustrates two fetus brain biased human lineage-specific hub genes (top) and two unbiased human lineage-specific hub genes (bottom) and their direct interacting partners from the human PPI network. Genes biased in fetus brain (blue), adult brain (red), and unbiased (orange) between fetus and adult brain are marked. Genes (in square circles) outlined in the green dashed rectangle have been reported to have some brain development-related functions in previous literature
Mentions: More intriguingly, four human-lineage specific (the genes that originated only in the human lineage since its divergence and thus exist only in the human genome) hub genes with clear expression evidence in human brain were found (Additional file 8: Table S4). As there was no direct clue in literatures about their functions in brain development of these four genes, we conducted a ‘guilt by connection’ study to investigate the reported evidence for the roles in brain function of their direct linking partners by manual curation of early studies (Additional file 9: Table S5). For instance, CCT4, a subunit of chaperonin containing TCP1, was reported to be involved with development of a brain malfunction disorder - Alzheimer’s disease [33], and it was also shown that CCT4 (gene id: 10575) is a direct interacting partner of one of young hub gene - FAM86B2 (gene id: 653333, Fig. 8). Collectively, we found that 62.5 % (10 of 16) and 53.3 % (8 of 15) of the first-layer linking partners for two out of the four hub genes, which were fetus brain biased, were confirmed to be involved in brain development (Fig. 8 and Additional file 9: Table S5). While for the other two unbiased hub genes, 24.4 % (10 out of 41) and 50 % (3 out of 6) were proven to function in brain development in previous literature (Fig. 8 and Additional file 9: Table S5). As genes with similar functions tend to be within the same network cluster [34], this evidence suggests these four human-lineage specific hub genes could also be with associated functions in human brain development.Fig. 8

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.