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Article Dans Une Revue Molecular Biology and Evolution Année : 2019

Accurate Tracking of the Mutational Landscape of Diploid Hybrid Genomes

Résumé

Mutations, recombinations and genome duplications may promote genetic diversity and trigger evolutionary processes. However, quantifying these events 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 insertions/deletions, copy-number variants, aneuploidies, and loss-of-heterozygosity. Pairs of haploid Saccharomyces parents were combined to generate ancestor hybrids with phased genomes and varying levels of heterozygosity. These diploids were evolved under different laboratory protocols, in particular mutation accumulation experiments. Variant simulations enabled the efficient integration of competitive and standard mapping of short reads, depending on local levels of heterozygosity. Experimental validations proved the high accuracy and resolution of our computational approach. Finally, applying MuLoYDH to four different diploids revealed striking genetic background effects. Homozygous S. cerevisiae showed a ∼4-fold higher mutation rate compared to its closely related species S. paradoxus. Intraspecies hybrids unveiled that a substantial fraction of the genome (∼250 bp per generation) was shaped by loss-of-heterozygosity, a process strongly inhibited in interspecies hybrids by high levels of sequence divergence between homologous chromosomes. In contrast, interspecies hybrids exhibited higher single-nucleotide mutation rates compared to intraspecies hybrids. MuLoYDH provided an unprecedented quantitative insight into the evolutionary processes that mould diploid yeast genomes and can be generalised to other genetic systems.

Dates et versions

hal-02381458 , version 1 (26-11-2019)

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Lorenzo Tattini, Nicolò Tellini, Simone Mozzachiodi, Melania d'Angiolo, Sophie Loeillet, et al.. Accurate Tracking of the Mutational Landscape of Diploid Hybrid Genomes. Molecular Biology and Evolution, 2019, 36 (12), pp.2861-2877. ⟨10.1093/molbev/msz177⟩. ⟨hal-02381458⟩
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