Regulation of protein abundance in genetically diverse mouse populations

Keele, G. R.; Zhang, T.; Pham, D. T.; Vincent, M.; Bell, T. A.; Hock, P.; Shaw, G. D.; Munger, S. C.; de Villena, F. P.-M.; Ferris, M. T.; Gygi, S. P.; Churchill, G. A.

doi:10.1101/2020.09.18.296657

bioRxiv · 10.1101/2020.09.18.296657

Regulation of protein abundance in genetically diverse mouse populations

Keele, G. R.·Zhang, T.·Pham, D. T.·Vincent, M.·Bell, T. A.·Hock, P.·Shaw, G. D.·Munger, S. C.·de Villena, F. P.-M.·Ferris, M. T.·Gygi, S. P.·Churchill, G. A.

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Abstract

Proteins constitute much of the structure and functional machinery of cells, forming signaling networks, metabolic pathways, and large multi-component complexes. Protein abundance is regulated at multiple levels spanning transcription, translation, recycling, and degradation to maintain proper balance and optimal function. To better understand how protein abundances are maintained across varying genetic backgrounds, we analyzed liver proteomes of three genetically diverse mouse populations. We observe strong concordance of genetic and sex effects across populations. Differences between the populations arise from the contributions of additive, dominance, and epistatic components of heritable variation. We find that the influence of genetic variation on proteins that form complexes relates to their co-abundance. We identify effects on protein abundance from mutations that arose and became fixed during breeding and can lead to unique regulatory responses and disease states. Genetically diverse mouse populations provide powerful tools for understanding proteome regulation and its relationship to whole-organism phenotypes. O_FIG O_LINKSMALLFIG WIDTH=196 HEIGHT=200 SRC="FIGDIR/small/296657v3_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1c8a941org.highwire.dtl.DTLVardef@e022b6org.highwire.dtl.DTLVardef@106e361org.highwire.dtl.DTLVardef@13a2c2c_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Keele, G. R., Zhang, T., Pham, D. T., Vincent, M., Bell, T. A., Hock, P., Shaw, G. D., Munger, S. C., de Villena, F. P.-M., Ferris, M. T., Gygi, S. P., Churchill, G. A.. 2020-09-18. Regulation of protein abundance in genetically diverse mouse populations. https://doi.org/10.1101/2020.09.18.296657

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