The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.
Graduate School of Biomedical Sciences, Tufts University, 136 Harrison Ave, Boston, MA, 02111, USA.
Chromosome Res. 2022 Sep;30(2-3):165-186. doi: 10.1007/s10577-022-09697-2. Epub 2022 Jul 13.
Meiotic drive occurs when one allele at a heterozygous site cheats its way into a disproportionate share of functional gametes, violating Mendel's law of equal segregation. This genetic conflict typically imposes a fitness cost to individuals, often by disrupting the process of gametogenesis. The evolutionary impact of meiotic drive is substantial, and the phenomenon has been associated with infertility and reproductive isolation in a wide range of organisms. However, cases of meiotic drive in humans remain elusive, a finding that likely reflects the inherent challenges of detecting drive in our species rather than unique features of human genome biology. Here, we make the case that house mice (Mus musculus) present a powerful model system to investigate the mechanisms and consequences of meiotic drive and facilitate translational inferences about the scope and potential mechanisms of drive in humans. We first detail how different house mouse resources have been harnessed to identify cases of meiotic drive and the underlying mechanisms utilized to override Mendel's rules of inheritance. We then summarize the current state of knowledge of meiotic drive in the mouse genome. We profile known mechanisms leading to transmission bias at several established drive elements. We discuss how a detailed understanding of meiotic drive in mice can steer the search for drive elements in our own species. Lastly, we conclude with a prospective look into how new technologies and molecular tools can help resolve lingering mysteries about the prevalence and mechanisms of selfish DNA transmission in mammals.
当一个杂合位点的等位基因以不成比例的方式进入功能配子，从而违反孟德尔的均等分离定律时，就会发生减数分裂驱动。这种遗传冲突通常会给个体带来适应度代价，通常是通过打乱配子发生过程来实现。减数分裂驱动的进化影响是巨大的，并且这种现象与广泛的生物的不孕和生殖隔离有关。然而，人类中的减数分裂驱动案例仍然难以捉摸，这一发现可能反映了在我们这个物种中检测驱动的固有挑战，而不是人类基因组生物学的独特特征。在这里，我们提出观点，即家鼠（Mus musculus）提供了一个强大的模型系统，可以研究减数分裂驱动的机制和后果，并促进关于驱动范围和潜在机制的转化推论。我们首先详细介绍了如何利用不同的家鼠资源来识别减数分裂驱动的案例，以及用于推翻孟德尔遗传规律的潜在机制。然后，我们总结了目前对鼠标基因组中减数分裂驱动的了解。我们对几个已建立的驱动元件中的遗传偏向传递机制进行了概述。我们讨论了如何通过深入了解老鼠中的减数分裂驱动，来引导我们在自身物种中寻找驱动元件的工作。最后，我们前瞻性地展望了新技术和分子工具如何帮助解决哺乳动物中自私 DNA 传递的普遍性和机制方面的遗留谜团。
