Studies On Adaptive Evolution Of Ascaris And Target Screening Of Antihelmintics

Ascaris parasitic in most vertebrates,threatening human,livestock and wildlife health.The migration of larvae in the host can cause visceral larva migrants(VLM).Additionally,ascaris infection can also cause intestinal obstruction,which can lead to the death of the host in severe cases.The previous study of ascaris mainly focus on individual infections,identification of morphological or molecular,and the study of some specific species.There is little known about the taxonomic status,evolution and differentiation history.Lack of understanding of the adaptive evolution in Ascaris.Therefore,it is of great significance for understanding the taxonomic status of ascaris,differentiation time,and the adaptive evolutionary characteristics of Ascaris to its host,it is also important for understanding the evolution of Ascaris and the preventing and controlling ascariasis.In this study,the complete mitochondrial genomes of ten Ascaris species were obtained.All available mitochondrial genes were used to construct the comprehensive phylogenetic tree of Ascaris.In addition,we estimate the divergence time between species.The complete genome sequences of six Ascaris species were then assembled,and the enrichment analysis was performed on expanded gene families of different Ascaris branch.The adaptive molecular characteristics of different ascaris were also analyzed.The whole-genome sequencing of Parascaris sp.in different regions and different hosts(domestic horses,zebras and donkeys)was performed for exploring the evolutionary relationship among different populations.It provides a reference for understanding the intraspecific evolution of Ascaris.Finally,we scanned the drug targets and potential drug target gene sets in the whole-genome using the genome resources of Ascaris,which provided an important reference for designing new anthelmintics in the future.The results are as follows:1.Complete circular mitochondrial genomes of eight Ascaris and two Heterakoidea were assembled in this study.The comprehensive phylogenetic tree was constructed using the mitochondrial gene sequences of all available Ascaris and Heterakoidea,which supports that the Ascaris family is divided into six different branches.2.The divergence of Ascaris and Heterakoidea during the Carboniferous period(300-360Mya).The early divergence of the common ancestor in these two families might experience gene rearrangement events,among them,tandem duplication/random loss(TDRL)is one of the major types of rearrangements.3.The genomes of six Ascaris species(Ascaris lumbricoides,Ophidascaris sp.,Porrocaecum sp.VI,Porrocaecum sp.RE,Ascaridia columbae and Ascaridia galli)were assembled and annotated using the third-generation sequencing technology.The genome size of six Ascaris ranged from 267 to 498 Mb,and the contents of repeat elements in Ascaris varied significantly(3.92% to 45.25%).We found that the content of repetitive sequences is one of the important reasons for the large genome size of the Ophidascaris sp.4.Gene family comparisons show significant expansion of metabolic pathways in Ascarididae.The Ophidascaris sp.have expanded significantly in autoimmunity-related pathways.The results indicated that the expansion of gene family may be closely related to Ascaris’ adaptation to different host intestinal environment and living habits.5.A recent differentiation process of P.univalens in horse(P.univalens of Equus caballus,PEc,n=19),zebra(P.univalens of Equus zebra,PEz,n=18)and donkey(P.univalens of Equus asinus,PEa,n=5)was reported.The evolutionary tree indicates that the P.univalens population is divided into two distinct branches,PEc population and the PEz&PEa population,and they were diverged almost 900-1500 years ago.In PEz&PEa clades,genes associated with glycolytic pathways were significantly selected.In PEc clade,some genes related to lipid metabolism pathway were selected significantly.6.Based on the existing Ascaris genome resources,a potential drug target screening protocol was designed at the whole genome level,which is suitable for the current Ascaris resource.Finally,a total of 24 known anthelmintic drug targets and 60 compounds related to drug targets with phase III/IV approval were identified,providing a basis reference for the designing a new anthelmintics in the future.In this study,the comprehensive studied was performed on Ascaris using mitochondrial sequence and whole genome sequence.The phylogenetic relationship and divergence time among various families of Ascaris were elucidated at the molecular level,Meanwhile,six high-quality complete genome sequences of Ascaris were obtained,and the adaptive evolution and differentiation characteristics among Ascaris were studied by whole genome genetic.Finally,the identification of potential drug targets provides a molecular basis for the designing a new anthelmintics.