Most duplicate genes are eliminated from a genome shortly after duplication, but those that remain are an important source of biochemical diversity. Here, I present evidence from genome-scale protein-protein interaction data, microarray expression data, and large-scale gene knockout data that this diversification is often asymmetrical: one duplicate usually shows significantly more molecular or...

There is great variation in the rates of sequence evolution among proteins encoded by the same genome. The strongest correlate of evolutionary rate is expression level: highly expressed proteins tend to evolve slowly. This observation has led to the proposal that a major determinant of protein evolutionary rate involves the toxic effects of protein that misfolds due to transcriptional and trans...

BACKGROUND Reverse-engineering gene networks from expression profiles is a difficult problem for which a multitude of techniques have been developed over the last decade. The yearly organized DREAM challenges allow for a fair evaluation and unbiased comparison of these methods. RESULTS We propose an inference algorithm that combines confidence matrices, computed as the standard scores from si...

The Cre/lox site-specific recombination system has emerged as an important tool for the generation of conditional somatic mouse mutants. This method allows one to control gene activity in space and time in almost any tissue of the mouse, thus opening new avenues for studying gene function and for establishing sophisticated animal models of human diseases. A major technical advance in terms of i...

Background: Recombination Activating Genes (RAG) mutated embryonic stem cells are (ES) cells which are unable to perform V (D) J recombination. These cells can be used for generation of immunodeficient mouse. Creating biallelic mutations by CRISPR/Cas9 genome editing has emerged as a powerful technique to generate site-specific mutations in different sequences. Ob...

ORP4L, a member of the Oxysterol-binding protein (OSBP) related-proteins (ORPs) family, has been shown crucial in cell survival. But its role in macrophage function and effect in atherosclerosis are not clear. The mouse lack of ApoE spontaneously develops atherosclerosis lesions on a high-fat diet, and the distribution of the atherosclerosis plaques is similar to human. Thus ApoE knockout mouse...

Although various norms for reciprocity-based cooperation have been suggested that are evolutionarily stable against invasion from free riders, the process of alternation of norms and the role of diversified norms remain unclear in the evolution of cooperation. We clarify the co-evolutionary dynamics of norms and cooperation in indirect reciprocity and also identify the indispensable norms for t...

MOTIVATION The phenotypes of knockout mice provide crucial information for understanding the biological functions of mammalian genes. Among various knockout phenotypes, lethality is of great interest because those involved genes play essential roles. With the availability of large-scale genomic data, we aimed to assess how well the integration of various genomic features can predict the lethal ...

As biologists delve deeper into genomics, gene regulation and subcellular interactions, the networks that regulate cell function can sometimes appear wildly and gratuitously elaborate, since it is known that enormous complexity is not necessary for basic cellular survival and function. Minimal cellular life is thought to require about ~300 genes, yet even E. coli have ~4000 genes. Gene knockout...

It has long been established that histamine plays a role as a mediator of inflammation. From numerous studies, it has been well known that the amine has many pharmacological actions on a variety of organs. To evaluate the role of histamine in pain perception, we generated HDC knockout mice using a gene targeting method. Histamine is a hydrophilic autacoid, and in most tissues it is stored and s...