Characterization of filarial parasite evolution through genome assembly and transcriptomic analysis of Brugia malayi and Brugia pahangi

Abstract

To study the chromosomal structure of filarial parasites, the genomes of Brugia malayi and Brugia pahangi were assembled using a combination of Illumina, PacBio and Oxford Nanopore sequencing. The assembly was able to reconstruct all of the major chromosomes, including the X chromosome, which comprised over 20% of the genome in both species. Male specific sequencing was used to identify contigs associated with the Y chromosome of B. malayi, and showed that these contigs contained the majority of the repetitive sequences in the genome. A chromosomal fusion of the sex chromosomes of these species that created a pseudoautosomal region of the X chromosome and a haploid region in males was also identified. Analysis of other filarial parasites revealed that while not all species had the same fusion, this haploid region was consistently conserved. In order to compare the chromosomes of these filarial species to other species whose genomes had not been assembled into chromosome form, a classification system called Nigon elements was created to assign large conserved syntenic blocks to specific Nigon elements that were comparable across species. A large reduction in nucleotide diversity across this region of the sex chromosome was also identified, indicating that the fusions were recent. Finally, short read transcriptomics identified novel microRNAs in B. malayi that originate from both the parasite and its Wolbachia endosymbiont. Target prediction across the mammalian portion of the parasite life cycle revealed seven major clusters of co-regulated genes, including a number of developmental and adult-specific gene pathways. Furthermore, in situ hybridization imaging confirmed that the microRNAs predicted to originate from the Wolbachia were not present in the parasite nuclei, suggesting that these sequences are bacterial in origin. These findings reveal a new co-evolving pathway for endosymbiont and parasite communication.