Abstract
Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Here, we report using PacBio long-read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome for the MHco3(ISE).N1 isolate. We show a remarkable pattern of conservation of chromosome content with Caenorhabditis elegans, but almost no conservation of gene order. Short and long-read transcriptome sequencing allowed us to define coordinated transcriptional regulation throughout the parasite’s life cycle and refine our understanding of cis- and trans-splicing. Finally, we provide a comprehensive picture of chromosome-wide genetic diversity both within a single isolate and globally. These data provide a high-quality comparison for understanding the evolution and genomics of Caenorhabditis and other nematodes and extend the experimental tractability of this model parasitic nematode in understanding helminth biology, drug discovery and vaccine development, as well as important adaptive traits such as drug resistance.
Highlights
Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens
We have built upon our previous assembly (version 1 (V1)23) using a hybrid approach, iteratively incorporating Illumina short-insert and 3 kbp libraries, Pacific Biosciences (PacBio) long-read, OpGen optical mapping, and 10X Genomics linked-read data (Supplementary Fig. 1; Supplementary Data 1) to generate a largely complete, chromosomal-scale genome assembly
We assigned chromosome names based on broad-scale synteny with C. elegans chromosomes (Fig. 1a); over 80% of 7,361 one-to-one orthologous genes are shared on syntenic chromosomes between the two species demonstrating the high conservation of genes per chromosome (Fig. 1b; top), vast rearrangements are evident and very little conservation of gene order remains (Fig. 1b; bottom)
Summary
Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Direct comparison of these assemblies shows discordance, revealing clear differences in gene family composition[25] and variation in assembly quality and gene content[26] Some of these differences reflect biological variation in this highly polymorphic species[27,28,29], many differences are technical artefacts, as revealed by comparing fragmented genome assemblies from sequencing DNA derived from pools of a genetically diverse organism. We provide insight into patterns of transcriptional change and putative co-regulation using a significantly improved genome annotation, derived de novo from both shortand long-read cDNA sequencing, and describe within- and between-population genetic diversity that shapes the genome This chromosome-scale assembly offers insight into genome evolution among a broad group of important parasite species and a robust scaffold for genome-wide analyses of important parasite traits such as anthelmintic resistance
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