Journal ArticleDOI
Dosage sensitivity and the evolution of gene families in yeast
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TLDR
The hypothesis that dominance is a by-product of physiology and metabolism rather than the result of selection to mask the deleterious effects of mutations is supported, as it is found that members of large gene families are rarely involved in complexes.Abstract:
According to what we term the balance hypothesis, an imbalance in the concentration of the subcomponents of a protein - protein complex can be deleterious(1). If so, there are two consequences: first, both underexpression and overexpression of protein complex subunits should lower fitness, and second, the accuracy of transcriptional co-regulation of subunits should reflect the deleterious consequences of imbalance. Here we show that all these predictions are upheld in yeast ( Saccharomyces cerevisiae). This supports the hypothesis(2,3) that dominance is a by-product of physiology and metabolism rather than the result of selection to mask the deleterious effects of mutations. Beyond this, single-gene duplication of protein subunits is expected to be harmful, as this, too, leads to imbalance. As then expected, we find that members of large gene families are rarely involved in complexes. The balance hypothesis therefore provides a single theoretical framework for understanding components both of dominance and of gene family size.read more
Citations
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Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction
TL;DR: Evidence is presented for a large class of non-oncogenes that are essential for cancer cell survival and present attractive drug targets and theoretical considerations for combining orthogonal cancer therapies are provided.
Journal ArticleDOI
The evolution of gene duplications: classifying and distinguishing between models.
TL;DR: A comprehensive classification of the models that are relevant to all stages of the evolution of gene duplications is presented, each of which predicts a unique combination of evolutionary dynamics and functional properties.
Journal ArticleDOI
Quantifying Absolute Protein Synthesis Rates Reveals Principles Underlying Allocation of Cellular Resources
TL;DR: This work presents a genome-wide approach, based on ribosome profiling, for measuring absolute protein synthesis rates, and reveals how general principles, important both for understanding natural systems and for synthesizing new ones, emerge from quantitative analyses of protein synthesis.
Journal ArticleDOI
Turning a hobby into a job: how duplicated genes find new functions.
Gavin C. Conant,Kenneth H. Wolfe +1 more
TL;DR: Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications, and in many cases the 'new' function of one copy is a secondary property that was always present, but that has been co-opted to a primary role after the duplication.
Journal ArticleDOI
Functional Divergence of Duplicated Genes Formed by Polyploidy during Arabidopsis Evolution
TL;DR: Functional diversification of the surviving duplicated genes is a major feature of the long-term evolution of polyploidy, and the rate of protein sequence evolution has been significantly asymmetric in >20% of duplicate pairs.
References
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Journal ArticleDOI
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
Stephen F. Altschul,Thomas L. Madden,Alejandro A. Schäffer,Jinghui Zhang,Zheng Zhang,Webb Miller,David J. Lipman +6 more
TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Journal ArticleDOI
Cluster analysis and display of genome-wide expression patterns
TL;DR: A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression, finding in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function.
Book
Genetics and Analysis of Quantitative Traits
Michael Lynch,Bruce Walsh +1 more
TL;DR: This book discusses the genetic Basis of Quantitative Variation, Properties of Distributions, Covariance, Regression, and Correlation, and Properties of Single Loci, and Sources of Genetic Variation for Multilocus Traits.