A genetic basis for a postmeiotic X versus Y chromosome intragenomic conflict in the mouse.
A genetic basis for a postmeiotic X versus Y chromosome intragenomic conflict in the mouse.
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DOI：
10.1371/journal.pgen.1002900
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发表时间：
2012-09
期刊：
影响因子：
4.5
通讯作者：
Burgoyne PS
中科院分区：
文献类型：
--
作者：
Cocquet J;Ellis PJ;Mahadevaiah SK;Affara NA;Vaiman D;Burgoyne PS
当一个遗传因素有利于自己的传播而损害他人时，基因组内的冲突就会出现。性染色体传递的冲突预计会影响基因组结构，基因调控和物种形成。在小鼠中，X-和Y-连锁多拷贝基因之间存在基因组内冲突一直被认为但从未得到证实。Y编码的多拷贝基因Sly已被证明在减数分裂后性染色质（PMSC）的表观遗传抑制中具有主导作用，因此，抑制X和Y基因，其中包括其X连锁同源物Slx和Slxl 1。在这里，我们产生了Sly和Slx/Slxl 1缺陷的小鼠，并观察到Slx/Slxl 1具有与Sly相反的作用，因为它刺激精子细胞中XY基因的表达。Slx/Slxl 1缺陷可挽救由Sly缺陷引起的精子分化缺陷和近不育，反之亦然。Slx/Slxl 1缺陷也会导致雄性后代的性别比例扭曲，这可以通过Sly缺陷来纠正。总之，我们的数据表明，Slx/Slxl 1和Sly在精子分化过程中具有拮抗作用，并参与减数分裂后的基因组内冲突，导致分离扭曲和雄性不育。毫无疑问，这是导致小鼠X和Y染色体上大量基因扩增的原因。这也可能是F1雄性杂种不育的基础，其中Slx/Slxl 1和Sly拷贝数之间的平衡以及因此表达被破坏。据我们所知，我们的工作是第一次证明哺乳动物中X和Y相关基因之间存在竞争。这也为基因组内冲突是影响基因表达、基因组结构和物种形成的重要进化力量的概念提供了生物学基础。一个基因的两个拷贝通常有相等的机会被遗传;然而，一些基因可以“自私地”传递给>50%的后代：一种被称为传递失真的现象。X或Y染色体上的扭曲基因分别导致雌性/雄性后代过多。这就在性染色体之间建立了一个“基因组冲突”（军备竞赛），可以从根本上影响它们的基因内容。失去部分Y染色体的雄性小鼠产生的雌性后代超过50%，并且X染色体上的多个基因过度激活，为畸变提供了强有力的间接证据。在这里，我们证明了存在的基因组冲突调节的基因Slx/Slxl 1和Sly，目前在X和Y染色体上分别为100至100个拷贝。SLX/SLXL 1和SLY蛋白对发育中精子的性染色体表达具有拮抗作用，并使后代性别比偏向雌性/雄性。有趣的是，虽然任何一个基因的缺乏都会导致严重的生育问题，但当两个基因都缺乏时，生育能力会得到改善。我们认为，Slx/Slxl 1和Sly参与的冲突导致了X和Y基因的扩增，并可能在小鼠物种形成中发挥了重要作用。
Intragenomic conflicts arise when a genetic element favours its own transmission to the detriment of others. Conflicts over sex chromosome transmission are expected to have influenced genome structure, gene regulation, and speciation. In the mouse, the existence of an intragenomic conflict between X- and Y-linked multicopy genes has long been suggested but never demonstrated. The Y-encoded multicopy gene Sly has been shown to have a predominant role in the epigenetic repression of post meiotic sex chromatin (PMSC) and, as such, represses X and Y genes, among which are its X-linked homologs Slx and Slxl1. Here, we produced mice that are deficient for both Sly and Slx/Slxl1 and observed that Slx/Slxl1 has an opposite role to that of Sly, in that it stimulates XY gene expression in spermatids. Slx/Slxl1 deficiency rescues the sperm differentiation defects and near sterility caused by Sly deficiency and vice versa. Slx/Slxl1 deficiency also causes a sex ratio distortion towards the production of male offspring that is corrected by Sly deficiency. All in all, our data show that Slx/Slxl1 and Sly have antagonistic effects during sperm differentiation and are involved in a postmeiotic intragenomic conflict that causes segregation distortion and male sterility. This is undoubtedly what drove the massive gene amplification on the mouse X and Y chromosomes. It may also be at the basis of cases of F1 male hybrid sterility where the balance between Slx/Slxl1 and Sly copy number, and therefore expression, is disrupted. To the best of our knowledge, our work is the first demonstration of a competition occurring between X and Y related genes in mammals. It also provides a biological basis for the concept that intragenomic conflict is an important evolutionary force which impacts on gene expression, genome structure, and speciation. Both copies of a gene have normally an equal chance of being inherited; however, some genes can act “selfishly” to be transmitted to >50% of offspring: a phenomenon known as transmission distortion. Distorting genes on the X or Y chromosome leads to an excess of female/male offspring respectively. This then sets up a “genomic conflict” (arms race) between the sex chromosomes that can radically affect their gene content. Male mice that have lost part of their Y produce >50% female offspring and show over-activation of multiple genes on the X, providing strong circumstantial evidence for distortion. Here, we demonstrate the existence of a genomic conflict regulated by the genes Slx/Slxl1 and Sly, present in ∼50 to 100 copies on the X and Y chromosomes respectively. SLX/SLXL1 and SLY proteins have antagonistic effects on sex chromosome expression in developing sperm and skew the offspring sex-ratio in favor of females/males. Interestingly, while deficiency of either gene alone leads to severe fertility problems, fertility is improved when both genes are deficient. We believe that the conflict in which Slx/Slxl1 and Sly are involved led to the amplification of X and Y genes and may have played an important role in mouse speciation.
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影响因子：
9.8
作者：
Church DM;Goodstadt L;Hillier LW;Zody MC;Goldstein S;She X;Bult CJ;Agarwala R;Cherry JL;DiCuccio M;Hlavina W;Kapustin Y;Meric P;Maglott D;Birtle Z;Marques AC;Graves T;Zhou S;Teague B;Potamousis K;Churas C;Place M;Herschleb J;Runnheim R;Forrest D;Amos-Landgraf J;Schwartz DC;Cheng Z;Lindblad-Toh K;Eichler EE;Ponting CP;Mouse Genome Sequencing Consortium
通讯作者：
Mouse Genome Sequencing Consortium
影响因子：
64.5
作者：
LYON, MF
通讯作者：
LYON, MF
影响因子：
3.5
作者：
Ellis, PJI;Clemente, EJ;Burgoyne, PS
通讯作者：
Burgoyne, PS
影响因子：
3.5
作者：
Ellis, Peter J. I.;Bacon, Joanne;Affara, Nabeel A.
通讯作者：
Affara, Nabeel A.
影响因子：
56.9
作者：
MARDON, G;MOSHER, R;PAGE, DC
通讯作者：
PAGE, DC