Genome structure and population genomics of the canine heartworm Dirofilaria immitis

• Published in: International journal for parasitology 2024-02, Vol.54 (2), p.89-98
• Main Authors: Gandasegui, Javier, Power, Rosemonde I., Curry, Emily, Lau, Daisy Ching-Wai, O'Neill, Connor M., Wolstenholme, Adrian, Prichard, Roger, Šlapeta, Jan, Doyle, Stephen R.
• Format: Article
• Language: English
• Subjects: Animals; Anthelmintic resistance; Australia; Brugia malayi; Canidae; chromosomes; Dirofilaria immitis; Dirofilaria immitis - genetics; Dirofilariasis - epidemiology; Dog Diseases - parasitology; Dogs; drugs; genetic variation; genome; Genome assembly; Genome, Helminth; heartworms; Italy; Lactones; Metagenomics; mortality; Onchocerca volvulus; parasitology; population genetics; Population genomics; principal component analysis; Whole-genome sequencing
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2023.07.006

[Display omitted] •We present a chromosome-scale genome assembly for the canine heartworm Dirofilaria immitis.•Comparative analyses with filarial nematodes reveal sex-linked and autosomal chromosomes, and chromosomal rearrangements.•Population genetics of diverse isolates shows broad genetic structure, but differences in diversity between regions.•Previously proposed variants associated with macrocyclic lactone resistance form two discrete clusters on chromosome 3. The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This study aimed to improve the genomic resources of D. immitis to enable a more precise understanding of how genetic variation is distributed within and between parasite populations worldwide, which will inform the likelihood and rate by which parasites, and in turn, resistant alleles, might spread. We have guided the scaffolding of a recently published genome assembly for D. immitis (ICBAS_JMDir_1.0) using the chromosomal-scale reference genomes of Brugia malayi and Onchocerca volvulus, resulting in an 89.5 Mb assembly composed of four autosomal- and one sex-linked chromosomal-scale scaffolds representing 99.7% of the genome. Publicly available and new whole-genome sequencing data from 32 D. immitis samples from Australia, Italy and the USA were assessed using principal component analysis, nucleotide diversity (Pi) and absolute genetic divergence (Dxy) to characterise the global genetic structure and measure within- and between-population diversity. These population genetic analyses revealed broad-scale genetic structure among globally diverse samples and differences in genetic diversity between populations; however, fine-scale subpopulation analysis was limited and biased by differences between sample types. Finally, we mapped single nucleotide polymorphisms previously associated with macrocyclic lactone resistance in the new genome assembly, revealing the physical linkage of high-priority variants on chromosome 3, and determined their frequency in the studied populations. This new chromosomal assembly for D. immitis now allows for a more precise investigation of selection on genome-wide genetic variation and will enhance our understanding of parasite trans