Evolutionarily diverged regulation of X-chromosomal genes as a primal event in mouse reproductive isolation.
Evolutionarily diverged regulation of X-chromosomal genes as a primal event in mouse reproductive isolation.
复制标题
DOI：
10.1371/journal.pgen.1004301
复制
发表时间：
2014-04
期刊：
影响因子：
4.5
通讯作者：
Shiroishi T
中科院分区：
文献类型：
--
作者：
Oka A;Takada T;Fujisawa H;Shiroishi T
基因调控不当与生殖隔离有关，但其遗传和分子基础尚不清楚。我们之前报道了一种小鼠亚特异性间X染色体替代菌株，由于精子发生时减数分裂进入中断，表现出雄性特异性不育的生殖隔离特征。在这里，我们通过微阵列对该菌株的睾丸细胞进行了全面的转录谱分析。结果清楚地揭示了取代供体X染色体中基因表达的严重失调。这种失调发生在可检测到的精子发生损伤之前，表明这是生殖隔离的原始事件。x连锁基因的失调表现为不对称；更多的基因不成比例地下调而不是上调。此外，这种失调随后可能通过级联有害效应导致常染色体基因整体转录调控的扰动。值得注意的是，通过引入与X染色体相同的供体菌株的1号染色体，这种转录失调基本上得到了恢复。这一发现表明，在反式中作用于x连锁靶基因的调控基因之一位于1号染色体上。本研究表明，调控不相容是导致X染色体替代菌株生殖隔离的主要原因。以雄性不育和生存能力下降为特征的生殖隔离对物种形成很重要，因为它抑制了两个分化种群之间的自由遗传交换，加速了遗传分化。杂交不育（杂交动物不育）是一种生殖隔离现象，可能是由两个不同种群带来的不同遗传因子之间的有害相互作用造成的。杂交动物不仅在蛋白质编码序列上存在多态性，而且在转录调控序列上也存在多态性。然而，杂种不育的确切遗传机制大多是未知的。在这里，我们报告了来自一个小鼠亚种的x连锁基因的表达在另一个亚种的遗传背景中很大程度上被错误调控。x连锁基因的错误表达随后影响了常染色体基因的整体表达。这些结果共同表明，两个小鼠亚种之间的杂交不育是由于转录调控回路中遗传不相容导致基因表达失调造成的。这种转录调控中的遗传不相容可能是一般生殖隔离的基础。
Improper gene regulation is implicated in reproductive isolation, but its genetic and molecular bases are unknown. We previously reported that a mouse inter-subspecific X chromosome substitution strain shows reproductive isolation characterized by male-specific sterility due to disruption of meiotic entry in spermatogenesis. Here, we conducted comprehensive transcriptional profiling of the testicular cells of this strain by microarray. The results clearly revealed gross misregulation of gene expression in the substituted donor X chromosome. Such misregulation occurred prior to detectable spermatogenetic impairment, suggesting that it is a primal event in reproductive isolation. The misregulation of X-linked genes showed asymmetry; more genes were disproportionally downregulated rather than upregulated. Furthermore, this misregulation subsequently resulted in perturbation of global transcriptional regulation of autosomal genes, probably by cascading deleterious effects. Remarkably, this transcriptional misregulation was substantially restored by introduction of chromosome 1 from the same donor strain as the X chromosome. This finding implies that one of regulatory genes acting in trans for X-linked target genes is located on chromosome 1. This study collectively suggests that regulatory incompatibility is a major cause of reproductive isolation in the X chromosome substitution strain. Reproductive isolation characterized by male sterility and decreased viability is important for speciation, because it suppresses free genetic exchange between two diverged populations and accelerates the genetic divergence. One of the reproductive isolation phenomena, hybrid sterility (sterility in hybrid animals), is possibly caused by deleterious interactions between diverged genetic factors brought by two distinct populations. The polymorphism not only in protein-coding sequences but also in transcriptional regulatory sequences can cause the genetic incompatibility in hybrid animals. However, the precise genetic mechanisms of hybrid sterility are mostly unknown. Here, we report that the expression of X-linked genes derived from one mouse subspecies was largely misregulated in the genetic background of another subspecies. The misregulated expression of the X-linked genes subsequently affected the global expression of autosomal genes. The results collectively indicate that hybrid sterility between the two mouse subspecies is caused by misregulation of gene expression due to genetic incompatibility in the transcriptional regulatory circuitry. Such genetic incompatibility in transcriptional regulation likely underlies reproductive isolation in general.
登录
查看更多内容
影响因子：
4
作者：
Gurbich TA;Bachtrog D
通讯作者：
Bachtrog D
影响因子：
3.3
作者：
Campbell, Polly;Good, Jeffrey M.;Nachman, Michael W.
通讯作者：
Nachman, Michael W.
影响因子：
30.8
作者：
Khil, PP;Smirnova, NA;Camerini-Otero, RD
通讯作者：
Camerini-Otero, RD
影响因子：
7
作者：
Goncalves A;Leigh-Brown S;Thybert D;Stefflova K;Turro E;Flicek P;Brazma A;Odom DT;Marioni JC
通讯作者：
Marioni JC
影响因子：
56.9
作者：
Mihola, Ondrej;Trachtulec, Zdenek;Forejt, Jiri
通讯作者：
Forejt, Jiri