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 Saccharomyces cerevisiae showed a ∼4-fold higher mutation rate compared with 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 with intraspecies hybrids. MuLoYDH provided an unprecedented quantitative insight into the evolutionary processes that mold diploid yeast genomes and can be generalized to other genetic systems.

中文翻译：

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二倍体杂交基因组突变景观的准确跟踪。

突变，重组和基因组重复可促进遗传多样性并触发进化过程。然而，量化二倍体杂种基因组中的这些事件是具有挑战性的。在这里，我们提出了一个集成的实验和计算工作流程，以根据单核苷酸变体，小的插入/缺失，拷贝数变体，非整倍性和杂合性缺失来准确跟踪酵母二倍体杂种（MuLoYDH）的突变态势。配对成对的单倍体酿酒酵母父母，以产生具有相控基因组和不同水平杂合度的祖先杂种。这些二倍体是在不同的实验室规程（尤其是突变积累实验）下进化而来的。多样化的模拟功能使短读段的竞争性和标准作图得以有效整合，取决于当地的杂合水平。实验验证证明了我们的计算方法具有很高的准确性和分辨率。最后，将MuLoYDH应用于四个不同的二倍体显示出惊人的遗传背景效应。纯合子酿酒酵母与其近缘种S. paradoxus相比，突变率高约4倍。种内杂种揭示了基因组的很大一部分（每代约250 bp）是由杂合性丧失形成的，杂种间杂种的这种过程由于同源染色体之间的高水平序列差异而强烈抑制了这一过程。相反，与种内杂种相比，种间杂种表现出更高的单核苷酸突变率。