Predicting the proportion of essential genes in mouse duplicates based on biased mouse knockout genes.
ABSTRACT In the yeast or nematode, the proportion of essential genes in duplicates is lower than in singletons (single-copy genes), due to the functional redundancy. One may expect that it should be the same in the mouse genome. However, based on the publicly available mouse knockout data, it was observed that the proportion of essential genes in duplicates is similar to that in singletons. The most straightforward interpretation, as claimed in a recent study, is that duplicate genes may have a negligible role in the mouse genetic robustness. Here we show that in the current mouse knockout dataset, recently duplicated genes have been highly underrepresented, leading to an overestimation of the proportion of essential genes in duplicates. After estimating the duplication time of mouse duplication events, we have developed a simple bias-correcting procedure and shown that the bias-corrected proportion of essential genes in mouse duplicates is significantly lower than that in singletons.
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ABSTRACT: Gene duplication is one of the major driving forces shaping genome and organism evolution and thought to be itself regulated by some intrinsic properties of the gene. Comparing the essential genes among mouse and human, we observed that the essential genes avoid duplication in mouse while prefer to remain duplicated in humans. In this study, we wanted to explore the reasons behind such differences in gene essentiality by cross-species comparison of human and mouse. Moreover, we examined essential genes that are duplicated in humans are functionally more redundant than that in mouse. The proportion of paralog pseudogenization of essential genes is higher in mouse than that of humans. These duplicates of essential genes are under stringent dosage regulation in human than in mouse. We also observed slower evolutionary rate in the paralogs of human essential genes than the mouse counterpart. Together, these results clearly indicate that human essential genes are retained as duplicates to serve as backed up copies that may shield themselves from harmful mutations.PLoS ONE 03/2015; 10(3):e0120784. DOI:10.1371/journal.pone.0120784 · 3.53 Impact Factor
PLoS Computational Biology 07/2014; 10(7):e1003758. DOI:10.1371/journal.pcbi.1003758 · 4.83 Impact Factor
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ABSTRACT: In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO) mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (P E ) between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD). Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity.BioMed Research International 01/2014; 2014:758672. DOI:10.1155/2014/758672 · 2.71 Impact Factor