Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control
| Autor: | Tony Nolan, Samantha M. O’Loughlin, Austin Burt, Andrea Crisanti, Silke Fuchs, Annie J Forster, Tania Dottorini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
AcademicSubjects/SCI01140
Conserved 0106 biological sciences AcademicSubjects/SCI00010 Anopheles Gene drive Malaria Mosquito Vectors QH426-470 AcademicSubjects/SCI01180 010603 evolutionary biology 01 natural sciences Genome DNA sequencing Conserved sequence 03 medical and health sciences Intergenic region Genetics Animals Molecular Biology Gene Conserved Sequence Genetics (clinical) 030304 developmental biology Investigation Comparative genomics 0303 health sciences qx_4 biology qu_4 biology.organism_classification wc_750 DNA binding site Evolutionary biology qx_510 AcademicSubjects/SCI00960 qu_450 qx_515 |
| Zdroj: | G3: Genes, Genomes, Genetics, Vol 11, Iss 6 (2021) G3: Genes|Genomes|Genetics |
| ISSN: | 2160-1836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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