Life Sciences Department, Barcelona Supercomputing Center (BSC), Jordi Girona, 29, 08034, Barcelona, Spain.
Mechanisms of Disease Program, Institute for Research in Biomedicine (IRB), The Barcelona Institute of Science and Technology, Barcelona, Spain.
BMC Biol. 2023 May 11;21(1):105. doi: 10.1186/s12915-023-01608-z.
Hybrids are chimeric organisms with highly plastic heterozygous genomes that may confer unique traits enabling the adaptation to new environments. However, most evolutionary theory frameworks predict that the high levels of genetic heterozygosity present in hybrids from divergent parents are likely to result in numerous deleterious epistatic interactions. Under this scenario, selection is expected to favor recombination events resulting in loss of heterozygosity (LOH) affecting genes involved in such negative interactions. Nevertheless, it is so far unknown whether this phenomenon actually drives genomic evolution in natural populations of hybrids. To determine the balance between selection and drift in the evolution of LOH patterns in natural yeast hybrids, we analyzed the genomic sequences from fifty-five hybrid strains of the pathogenic yeasts Candida orthopsilosis and Candida metapsilosis, which derived from at least six distinct natural hybridization events.
We found that, although LOH patterns in independent hybrid clades share some level of convergence that would not be expected from random occurrence, there is an apparent lack of strong functional selection. Moreover, while mitosis is associated with a limited number of inter-homeologous chromosome recombinations in these genomes, induced DNA breaks seem to increase the LOH rate. We also found that LOH does not accumulate linearly with time in these hybrids. Furthermore, some C. orthopsilosis hybrids present LOH patterns compatible with footprints of meiotic recombination. These meiotic-like patterns are at odds with a lack of evidence of sexual recombination and with our inability to experimentally induce sporulation in these hybrids.
Our results suggest that genetic drift is the prevailing force shaping LOH patterns in these hybrid genomes. Moreover, the observed LOH patterns suggest that these are likely not the result of continuous accumulation of sporadic events-as expected by mitotic repair of rare chromosomal breaks-but rather of acute episodes involving many LOH events in a short period of time.
杂种是具有高度可塑性杂合基因组的嵌合体生物，这些基因组可能赋予其独特的特征，使其能够适应新环境。然而，大多数进化理论框架预测，来自不同亲本的杂种中存在高水平的遗传杂合性，很可能导致许多有害的上位性相互作用。在这种情况下，选择预计会有利于导致杂合性丢失（LOH）的重组事件，从而影响涉及这些负面相互作用的基因。然而，迄今为止，人们尚不清楚这种现象是否真的会推动自然种群杂种的基因组进化。为了确定自然酵母杂种中 LOH 模式进化过程中选择和漂变之间的平衡，我们分析了来自致病性酵母近平滑假丝酵母和中间假丝酵母的 55 个杂交菌株的基因组序列，这些菌株至少来自六个不同的自然杂交事件。
我们发现，尽管独立杂交枝系中的 LOH 模式存在一定程度的趋同，这与随机发生的情况不符，但明显缺乏强有力的功能选择。此外，虽然有丝分裂与这些基因组中少数同源染色体间的重组有关，但诱导的 DNA 断裂似乎会增加 LOH 率。我们还发现，这些杂种中的 LOH 不会随时间呈线性积累。此外，一些近平滑假丝酵母的杂种存在与减数分裂重组痕迹相符的 LOH 模式。这些类似减数分裂的模式与缺乏性重组的证据以及我们无法在这些杂种中实验诱导孢子形成的事实相矛盾。
我们的结果表明，遗传漂变是塑造这些杂种基因组中 LOH 模式的主要力量。此外，观察到的 LOH 模式表明，这可能不是偶然事件连续积累的结果，正如罕见染色体断裂的有丝分裂修复所预期的那样，而是在短时间内涉及许多 LOH 事件的急性发作的结果。
