Evolutionary breakpoints in the gibbon suggest association between cytosine methylation and karyotype evolution.
Evolutionary breakpoints in the gibbon suggest association between cytosine methylation and karyotype evolution.
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DOI：
10.1371/journal.pgen.1000538
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发表时间：
2009-06
期刊：
影响因子：
4.5
通讯作者：
de Jong PJ
中科院分区：
文献类型：
--
作者：
Carbone L;Harris RA;Vessere GM;Mootnick AR;Humphray S;Rogers J;Kim SK;Wall JD;Martin D;Jurka J;Milosavljevic A;de Jong PJ
自1500万至1800万年前从共同的人科动物祖先分化出来以来，巨猿物种积累了异常高数量的染色体变化。这种染色体重排率增加的原因尚不清楚，也不知道基因组结构是否起作用。为了解决这一问题，我们分析了北方白颊长臂猿（Nomenyl. leucogenys）和人类。我们发现断点区域富含片段性重复和重复，其中Alu元件最为丰富。位于碱基断裂点（<150 bp）附近的Alus比其它Alus具有更高的CpG含量。亚硫酸氢盐等位基因测序显示，这些长臂猿Alus的甲基化胞嘧啶平均密度低于其人类直系同源物。较高的CpG含量和较低的平均CpG甲基化的发现表明，表观遗传学上的gimalalu元件是不同于他们的人类直系同源物。甲基化不足和长臂猿染色体重排之间的关联表明，进化过程中表观遗传状态和结构基因组变异之间存在相关性。哺乳动物的基因组非常稳定（除了少数例外）。在人类中，错误的重组事件很少发生，表现为基因组疾病或癌症。在特殊情况下，基因组进化的速度已经被全基因组重组事件加速，从而产生一些高度衍生的核型。长臂猿物种（长臂猿科）的基因组是基因组结构进化加速的一个例子;长臂猿的染色体进化速率比哺乳动物的默认速率高出10-20倍（每400万年发生一次染色体变化）。由于我们有兴趣调查这种现象的可能遗传原因，我们对北方白颊长臂猿基因组中相当数量的染色体断裂点进行了测序，并分析了这些位点的基因组特征。我们观察到，gigabacterium断点主要与内源性反转录转座子称为Alus，这是通常丰富的灵长类动物的基因组。此外，我们的分析表明，与直链人Alus相比，giganocalus具有较低的甲基化CpG含量。在哺乳动物中，已知CpG甲基化负责使逆转录转座子保持在受抑制状态并保护基因组完整性。因此，我们认为甲基化装置中的一个小故障可能驱动了长臂猿更高的基因组重组。
Gibbon species have accumulated an unusually high number of chromosomal changes since diverging from the common hominoid ancestor 15–18 million years ago. The cause of this increased rate of chromosomal rearrangements is not known, nor is it known if genome architecture has a role. To address this question, we analyzed sequences spanning 57 breaks of synteny between northern white-cheeked gibbons (Nomascus l. leucogenys) and humans. We find that the breakpoint regions are enriched in segmental duplications and repeats, with Alu elements being the most abundant. Alus located near the gibbon breakpoints (<150 bp) have a higher CpG content than other Alus. Bisulphite allelic sequencing reveals that these gibbon Alus have a lower average density of methylated cytosine that their human orthologues. The finding of higher CpG content and lower average CpG methylation suggests that the gibbon Alu elements are epigenetically distinct from their human orthologues. The association between undermethylation and chromosomal rearrangement in gibbons suggests a correlation between epigenetic state and structural genome variation in evolution. Mammalian genomes are remarkably stable (with few exceptions). In humans, wrong recombination events occur quite rarely, manifesting themselves in genomic disorders or cancer. On exceptional occasions, the rate of genome evolution has been accelerated by genome-wide reshuffling events giving rise to some highly derivative karyotypes. The genomes of gibbon species (Hylobatidae) are an example of accelerated genome structural evolution; gibbons display a rate of chromosome evolution 10–20 fold higher than the default rate found in mammals (one chromosome change every 4 million years). As we are interested in investigating the possible genetic causes of this phenomenon, we sequenced a considerable number of chromosomal breakpoints in the northern white-cheeked gibbon genome and analyzed the genomic features of these sites. We observe that the gibbon breakpoints are mostly associated with endogenous retrotransposons called Alus, which are normally abundant in the genomes of primates. Furthermore, our analysis revealed that gibbon Alus have a lower content of methylated CpG when compared to the orthologous human Alus. In mammals, CpG methylation is known to be responsible for keeping retrotransposons in a repressed state and protect genome integrity. We therefore suggest that a glitch in the methylation apparatus might have driven the higher genome recombination in gibbons.
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通讯作者：
de Jong PJ