Patterns and mechanisms of sex ratio distortion in the Collaborative Cross mouse mapping population.

Patterns and mechanisms of sex ratio distortion in the Collaborative Cross mouse mapping population.
复制标题

协作交叉小鼠绘图群体中性别比例扭曲的模式和机制。

DOI:
10.1093/genetics/iyab136
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发表时间:
2021
期刊:
影响因子:
3.3
通讯作者:
Dumont,BethL
Dumont,BethL
中科院分区:
生物学2区
文献类型:
--
作者:
Haines,BrettA;Barradale,Francesca;Dumont,BethL

文献摘要

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在具有单位点、基于染色体的性别决定机制的物种中,分离定律预测出生时雌性与雄性的比例相等。在这里,我们表明,在8路重组近交协作杂交(CC)小鼠种群中,与孟德尔期望的背离是司空见惯的。超过三分之一的CC菌株在断奶时表现出明显的性别比例扭曲(SRD),雄性偏向型菌株是雌性偏向型菌株的两倍。研究表明,这些普遍存在的性别偏见在多种繁殖环境中持续存在,随着时间的推移保持稳定,并且不受随机母体效应的影响。SRD表现出遗传成分,但QTL定位分析没有发现任何大的影响位点。这些发现,再加上CC创始菌株中没有性别比例偏差的报道,表明SRD表现为仅在重组CC基因组中发现的等位基因的多位点组合。我们探索了SRD的几种潜在的复杂遗传机制,包括导致性别偏向致死的等位基因相互作用、遗传性别逆转、由性别相关的自私元素介导的染色体驱动,以及特定的母亲和父亲基因型之间的不相容。我们的研究表明,没有一种机制能对这种人口范围内的SRD提供单一的解释。相反,我们的数据提供了SRD在不同菌株中发挥作用的不同机制的初步证据。综上所述,我们的工作揭示了SRD在CC人群中的普遍性,并将CC作为研究偏性染色体传播的各种遗传原因的有力资源。
In species with single-locus, chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, and are not mediated by random maternal effects. SRD exhibits a heritable component, but QTL mapping analyses fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We explore several potential complex genetic mechanisms for SRD, including allelic interactions leading to sex-biased lethality, genetic sex reversal, chromosome drive mediated by sex-linked selfish elements, and incompatibilities between specific maternal and paternal genotypes. We show that no one mechanism offers a singular explanation for this population-wide SRD. Instead, our data present preliminary evidence for the action of distinct mechanisms of SRD at play in different strains. Taken together, our work exposes the pervasiveness of SRD in the CC population and nominates the CC as a powerful resource for investigating diverse genetic causes of biased sex chromosome transmission.