DNA sequences that are exactly conserved over long evolutionary time scales have been observed in a variety of taxa. Such sequences are likely under strong functional constraint and they have been useful in the field of comparative genomics for identifying genome regions with regulatory function. A potential new application for these ultra-conserved elements has emerged in the development of gene drives to control mosquito populations. Many gene drives work by recognising and inserting at a specific target sequence in the genome, often imposing a reproductive load as a consequence. They can therefore select for target sequence variants that provide resistance to the drive. Focusing on highly conserved, highly constrained sequences lowers the probability that variant, gene drive-resistant alleles can be tolerated. Here we search for conserved sequences of 18bp and over in an alignment of 21 Anopheles genomes, spanning an evolutionary timescale of 100 million years, and characterise the resulting sequences according to their location and function. Over 8000 ultra-conserved elements were found across the alignment, with a maximum length of 164 bp. Length-corrected gene ontology analysis revealed that genes containing Anopheles ultra-conserved elements were over-represented in categories with structural or nucleotide binding functions. Known insect transcription factor binding sites were found in 48% of intergenic Anopheles ultra-conserved elements. When we looked at the genome sequences of 1142 wild-caught mosquitoes we found that 15% of the Anopheles ultra-conserved elements contained no polymorphisms. Our list of Anopheles ultra-conserved elements should provide a valuable starting point for the selection and testing of new targets for gene-drive modification in the mosquitoes that transmit malaria.

中文翻译：

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高度多样化的按蚊蚊子基因组中的超保守序列，对控制疟疾媒介具有重要意义。

在各种分类中已经观察到在长的进化时间尺度上完全保守的DNA序列。这样的序列可能在强大的功能约束下，并且它们在比较基因组学领域中用于鉴定具有调节功能的基因组区域是有用的。这些超保守元件的潜在新应用已经出现在控制蚊子种群的基因驱动开发中。许多基因驱动通过识别并插入基因组中的特定靶序列而发挥作用，因此通常会产生生殖负担。因此，他们可以选择对驱动器具有抵抗力的目标序列变体。专注于高度保守，高度受限制的序列降低了可以耐受变异的基因驱动抗性等位基因的可能性。在这里，我们在21个按蚊基因组的比对中搜索18bp以上的保守序列，跨越1亿年的进化时间尺度，并根据其位置和功能表征所得序列。在整个比对中发现超过8000个超保守元件，最大长度为164 bp。长度校正的基因本体分析显示，含有按蚊超保守元件的基因在具有结构或核苷酸结合功能的类别中被过度代表。在48％的基因间按蚊超保守元件中发现了已知的昆虫转录因子结合位点。当我们查看1142只野生蚊子的基因组序列时，我们发现15％的按蚊超保守元件没有多态性。