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• W2908162244 startingPage "507830" @default.
• W2908162244 abstract "Genome evolution promotes diversity within a population via mutations, recombination, and whole-genome duplication. However, quantifying precisely these factors in diploid hybrid genomes is challenging. Here we present an integrated experimental and computational workflow to accurately track the mutational landscape of yeast diploid hybrids (MuLoYDH) in terms of single-nucleotide variants, small insertion and deletions, copy-number variants and loss-of-heterozygosity. Haploid Saccharomyces parents are combined into diploid hybrids with fully phased genome and controlled levels of heterozygosity. The resulting hybrid represents the ancestral state and is evolved under different laboratory protocols. Variant simulations enable to efficiently integrate competitive and standard mapping, depending on local levels of heterozygosity and read length. Experimental validation in a mutator background proves the high accuracy and resolution of our computational approach. The unbiased estimation of mutation rates across different hybrids reveals striking genetic background effects. Surprisingly, homozygous S. cerevisiae shows ∼4-fold higher mutation rate compared to its sister species S. paradoxus. In contrast, interspecies hybrids exhibit mutation rate similar to intraspecies hybrids despite 10-fold higher heterozygosity. MuLoYDH reveals that a substantial fraction of the genome (∼200 bp per generation) is continuously shaped by loss-of-heterozygosity and this process is strongly inhibited by high levels of heterozygosity. We report a comprehensive framework for characterizing the mutational spectrum of yeast diploid hybrids with unprecedented resolution, which can be generalised to other genetic systems. Applying MuLoYDH to laboratory-evolved hybrids provides novel quantitative insights into the evolutionary processes that mould yeast genomes." @default.
• W2908162244 created "2019-01-11" @default.
• W2908162244 creator A5016176869 @default.
• W2908162244 creator A5026151739 @default.
• W2908162244 creator A5029468853 @default.
• W2908162244 creator A5029927126 @default.
• W2908162244 creator A5056422974 @default.
• W2908162244 creator A5086587266 @default.
• W2908162244 creator A5088349709 @default.
• W2908162244 date "2018-12-28" @default.
• W2908162244 modified "2023-09-24" @default.
• W2908162244 title "Accurate tracking of the mutational landscape of diploid hybrid genomes reveals genetic background effects" @default.
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• W2908162244 hasPublicationYear "2018" @default.

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