Pooled resequencing of larvae and adults reveals genomic variations associated with Ostreid herpesvirus 1 resistance in the Pacific oyster Crassostrea gigas

Abstract

The Ostreid herpesvirus 1 (OsHV-1) is a lethal pathogen of the Pacific oyster (Crassostrea gigas), an important aquaculture species. To understand the genetic architecture of the defense against the pathogen, we studied genomic variations associated with herpesvirus-caused mortalities by pooled whole-genome resequencing of before and after-mortality larval samples as well as dead and surviving adults from a viral challenge. Analysis of the resequencing data identified 5,271 SNPs and 1,883 genomic regions covering 3,111 genes in larvae, and 18,692 SNPs and 28,314 regions covering 4,863 genes in adults that were significantly associated with herpesvirus-caused mortalities. Only 1,653 of the implicated genes were shared by larvae and adults, suggesting that the antiviral response or resistance in larvae and adults involves different sets of genes or differentiated members of expanded gene families. Combined analyses with previous transcriptomic data from challenge experiments revealed that transcription of many mortality-associated genes was also significantly upregulated by herpesvirus infection confirming their importance in antiviral response. Key immune response genes especially those encoding antiviral receptors such as TLRs and RLRs displayed strong association between variation in regulatory region and herpesvirus-caused mortality, suggesting they may confer resistance through transcriptional modulation. These results point to previously undescribed genetic mechanisms for disease resistance at different developmental stages and provide candidate polymorphisms and genes that are valuable for understanding antiviral immune responses and breeding for herpesvirus resistance.

Epigenetic then genetic variations underpin rapid adaptation of oyster populations (Crassostrea gigas) to Pacific Oyster Mortality Syndrome (POMS)

“…Genes involved in these immune processes have been identified ( Fig. 3A ) and participate in the JAK/STAT pathways (UBA2, RNF220), the RLR/STING pathway (TRIM33, TBK1, IRF), the NF-KB pathway (TIRprot, NF-KB, MyD88), RNAi (DICER), and autophagy (ATG4), as well as several pathogen recognition receptors, such as DSCAM, Mannose Receptors, C1q, and PRGP 39 , consistent with previous studies demonstrating the polygenic nature of POMS resistance at the genetic level 14-16,40 . The POMS resistance phenotype involves antiviral genes and pathways, either constitutively expressed 41 and up-regulated faster in response to POMS in resistant families 9 , or environmentally induced 19-21 .…”

“…The SNP associated with the binary trait was mapped on chromosome 6 in a gene encoding the SUMO-activating enzyme subunit 2 (CGI_10018487), and the SNP associated with the semi-quantitative trait was mapped on the chromosome 4 in a gene of unknown function (CGI_10022698). Given the low number of significant SNPs identified and the polygenic architecture of POMS resistance [14][15][16] , we extended our analysis to suggestive SNPs (P-value < 0.0005), which led to the identification of 113 and 112 SNPs associated with the binary and semi-quantitative traits, respectively (Data S3 and S4). Among these 225 SNPs, 186 of which are non-redundant, 39 were in common, and 74 and 73 were specific to the binary and semi-quantitative traits, respectively (Fig.…”

“…Disease susceptibility has a heritable component [12][13][14] . Genome-wide association studies (GWA) have revealed that disease resistance has a polygenic architecture [14][15][16] . But oyster resistance to POMS is also dependent of oyster life-history, such as age 17,18 , and past exposure to pathogen elicitors 19,20 .…”

Epigenetic variations are more substantial than genetic variations in rapid adaptation of oyster to Pacific oyster mortality syndrome

“…The SNP associated with the binary trait was mapped on chromosome 6 in a gene encoding the SUMO-activating enzyme subunit 2 also known as UBA2 (CGI_10018487), and the SNP associated with the semiquantitative trait was mapped on chromosome 4 in a gene of unknown function (CGI_10022698). Given the low number of significant SNPs identified and the polygenic architecture of POMS resistance (15)(16)(17), we extended our analysis to suggestive SNPs (P < 0.0005; false discovery rate, FDR < 0.9), which led us to the identification of 113 and 112 SNPs associated with the binary and semiquantitative traits, respectively (data S3 and S4). Among these 225 SNPs, 186 of which were nonredundant, 39 were in common, and 74 and 73 were specific to the binary and semiquantitative traits, respectively (Fig.…”

“…Disease susceptibility has a heritable component (13)(14)(15). Genome-wide association (GWA) mapping has revealed that disease resistance has a polygenic architecture (15)(16)(17). However, oyster resistance to POMS is also dependent on oyster life history, such as age (18,19), and past exposure to pathogen elicitors (20,21).…”