Finding divergent sequences of homomorphic sex chromosomes via diploidized nanopore-based assembly from a single male.
Finding divergent sequences of homomorphic sex chromosomes via diploidized nanopore-based assembly from a single male.
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通过来自单个雄性的基于二倍化纳米孔的组装来寻找同态性染色体的不同序列。
DOI：
10.1101/2024.02.29.582759
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Rašić,Gordana
中科院分区：
文献类型：
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作者：
Filipović,Igor;Marshall,JohnM;Rašić,Gordana
尽管同型性染色体可以具有在其互补序列之间具有升高的序列分歧的非重组区域，但是这样的分歧信号可能难以生物信息学检测。如果在例如昆虫害虫的基因组中发现，这些序列可以被工程化的遗传性别鉴定和控制系统靶向。在这里，我们报告了一种方法，可以利用单个XY男性的长读纳米孔测序来识别同态性染色体的不同区域。长读段数据用于从头基因组组装，其以使其单倍体互补体之间的性别特异性差异最大化的方式二倍体化。我们表明，正确的组装定相是由来自男性的单倍体Y-轴承精子细胞的纳米孔读数的映射支持的。该方法揭示了埃及伊蚊（最重要的虫媒病毒载体）同形性染色体着丝粒附近的高度分歧区域（HDR），人们对创造新的遗传控制工具产生了极大的兴趣。HDR位于1号染色体上已知的雄性决定基因座下游约5 Mb处，并且显著富集卵巢偏向基因。虽然HDR中的重组相对较近（约1.4 MYA）停止，但HDR配子体具有不同的蛋白质编码基因的外显子和内含子，并且大多数lncRNA基因成为X特异性的。大量以前看不见的性连锁序列为控制这种致命蚊子的遗传系统的工程设计提供了新的假定目标。从广义上讲，我们的方法扩展了研究性染色体的神秘结构的工具箱。
Although homomorphic sex chromosomes can have non-recombining regions with elevated sequence divergence between its complements, such divergence signals can be difficult to detect bioinformatically. If found in genomes of e.g. insect pests, these sequences could be targeted by the engineered genetic sexing and control systems. Here, we report an approach that can leverage long-read nanopore sequencing of a single XY male to identify divergent regions of homomorphic sex chromosomes. Long-read data are used for de novo genome assembly that is diploidized in a way that maximizes sex-specific differences between its haploid complements. We show that the correct assembly phasing is supported by the mapping of nanopore reads from the male’s haploid Y-bearing sperm cells. The approach revealed a highly divergent region (HDR) near the centromere of the homomorphic sex chromosome of Aedes aegypti, the most important arboviral vector, for which there is a great interest in creating new genetic control tools. HDR is located ~5Mb downstream of the known male-determining locus on chromosome 1 and is significantly enriched for ovary-biased genes. While recombination in HDR ceased relatively recently (~1.4 MYA), HDR gametologs have divergent exons and introns of protein coding genes, and most lncRNA genes became X-specific. Megabases of previously invisible sex-linked sequences provide new putative targets for engineering the genetic systems to control this deadly mosquito. Broadly, our approach expands the toolbox for studying cryptic structure of sex chromosomes.