PMC:5118444 / 35167-37410
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5118444","sourcedb":"PMC","sourceid":"5118444","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5118444","text":"Network centrality of CNV genes\nProtein centrality in PPI networks has been correlated with evolutionary rate and essentiality of genes in several species (Hahn and Kern, 2005). Proteins that are more central in PPI networks tend to evolve more slowly and be more essential. As shown above, CNV genes show a tendency to evolve more rapidly and are under reduced selective constraint. Therefore, it follows that the products of genes overlapped by CNV may be less central in PPI networks.\nWe tested this hypothesis using PPI data from the STRING database. We found that, in general, the number of interactors (i.e., the network node degree) for all CNV genes with ≥ 1 interaction was not significantly lower compared to neutral genes with ≥ 1 interaction (one-tailed Wilcoxon rank-sum test, P = 0.9137). Taking a closer look, we found that duplication genes did have significantly smaller numbers of interactors compared to neutral genes (one-tailed Wilcoxon rank-sum test, P = 0.0208), while deletion genes and mixed genes did not exhibit significantly lower numbers of interactors (P = 0.99 and P = 0.62, respectively). This finding is consistent with results in fly (Dopman and Hartl, 2007) and yeast (Li et al., 2006) in which products of duplicated genes were shown to have reduced network connectivity.\nIt is possible that a gene's copy number status may reveal information about its essentiality in PPI networks. The results above suggest that genes with lower network centrality may be more likely to have duplicates that are retained during evolution. We have shown that duplication genes are subject to reduced selective constraint, and as a result, they tend to undergo more rapid sequence evolution. Genes with high centrality in PPI networks may be more evolutionarily constrained since changes in protein coding could hinder the ability of the resulting protein to form interactions with other proteins in the network. Therefore, as hypothesized by Dopman and Hartl (2007), the set of genes with low numbers of interactions in PPI networks, populated by duplication genes in cattle, fly, and yeast, may experience reduced pleiotropy, and consequently be robust to structural mutations as well as less constrained during evolution.","divisions":[{"label":"title","span":{"begin":0,"end":31}},{"label":"p","span":{"begin":32,"end":487}},{"label":"p","span":{"begin":488,"end":1307}}],"tracks":[{"project":"2_test","denotations":[{"id":"27920798-15616139-33484713","span":{"begin":171,"end":175},"obj":"15616139"},{"id":"27920798-18056801-33484714","span":{"begin":1187,"end":1191},"obj":"18056801"},{"id":"27920798-16980576-33484715","span":{"begin":1215,"end":1219},"obj":"16980576"},{"id":"27920798-18056801-33484716","span":{"begin":1980,"end":1984},"obj":"18056801"}],"attributes":[{"subj":"27920798-15616139-33484713","pred":"source","obj":"2_test"},{"subj":"27920798-18056801-33484714","pred":"source","obj":"2_test"},{"subj":"27920798-16980576-33484715","pred":"source","obj":"2_test"},{"subj":"27920798-18056801-33484716","pred":"source","obj":"2_test"}]},{"project":"MyTest","denotations":[{"id":"27920798-15616139-33484713","span":{"begin":171,"end":175},"obj":"15616139"},{"id":"27920798-18056801-33484714","span":{"begin":1187,"end":1191},"obj":"18056801"},{"id":"27920798-16980576-33484715","span":{"begin":1215,"end":1219},"obj":"16980576"},{"id":"27920798-18056801-33484716","span":{"begin":1980,"end":1984},"obj":"18056801"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"27920798-15616139-33484713","pred":"source","obj":"MyTest"},{"subj":"27920798-18056801-33484714","pred":"source","obj":"MyTest"},{"subj":"27920798-16980576-33484715","pred":"source","obj":"MyTest"},{"subj":"27920798-18056801-33484716","pred":"source","obj":"MyTest"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ecb993","default":true},{"id":"MyTest","color":"#9f93ec"}]}]}}