The whale shark genome reveals patterns of vertebrate gene family evolution

Abstract

Chondrichthyes (cartilaginous fishes) are fundamental for understanding vertebrate evolution, yet their genomes are understudied. We report long-read sequencing of the whale shark genome to generate the best gapless chondrichthyan genome assembly yet with higher contig contiguity than all other cartilaginous fish genomes, and studied vertebrate genomic evolution of ancestral gene families, immunity, and gigantism. We found a major increase in gene families at the origin of gnathostomes (jawed vertebrates) independent of their genome duplication. We studied vertebrate pathogen recognition receptors (PRRs), which are key in initiating innate immune defense, and found diverse patterns of gene family evolution, demonstrating that adaptive immunity in gnathostomes did not fully displace germline-encoded PRR innovation. We also discovered a new Toll-like receptor (TLR29) and three NOD1 copies in the whale shark. We found chondrichthyan and giant vertebrate genomes had decreased substitution rates compared to other vertebrates, but gene family expansion rates varied among vertebrate giants, suggesting substitution and expansion rates of gene families are decoupled in vertebrate genomes. Finally, we found gene families that shifted in expansion rate in vertebrate giants were enriched for human cancer-related genes, consistent with gigantism requiring adaptations to suppress cancer.

Teleost NOD-like receptors and their downstream signaling pathways: A brief review

“…The same study has also shown high expression of these genes in immune tissues and their significant response to bacterial/viral ligands. The presence of NLRs has been predicted in chondrichthyes such as grey bamboo shark [34] , whale shark [35] and major ray-finned fishes like bichir, American paddlefish, alligator gar, spotted gar and bowfin [36] following in silico analysis. In teleosts, whole genome sequencing along with advanced bioinformatics tools has facilitated the identification of several NLR transcripts over the years ( Table 1 ) having similar domain architecture to mammals.…”

Exploration of the Nurse Shark (Ginglymostoma cirratum) Plasma Immunoproteome Using High-Resolution LC-MS/MS

“…Transcriptome completeness was assessed using BUSCO v.3.0.2 ( 34 , 35 ) against the vertebrata Odb10 database. 83.5% complete orthologs were recovered ( Supplementary Table S4 ), comparing favourably to the most recent whale shark genome assembly ( 56 ), which showed a completeness of 78.7% using the same approach. This confirmed that our new transcriptome is an appropriate reference database for high-throughput proteomics in nurse shark, while further representing a useful resource available for future investigations.…”

“…Consequently, plasma proteomics offers a useful approach to inform on immunological functions. To date, very little is known about the plasma proteins of cartilaginous fishes or their individual contribution to immune defence, with studies primarily addressing their identification and evolution at the genomic level rather than their presence in plasma and associated immune responsiveness (e.g., 22 – 24 ). Where functional studies have been performed, these have focused on Igs (e.g., 4 , 25 ) or individual proteins that are present at high abundance in shark plasma, e.g., haptoglobin and hemopexin ( 6 , 26 ).…”

Uncovering a 500 million year old history and evidence of pseudogenization for TLR15

“…Despite being first described as a member of the TLR1 family ( 8 ), some authors have since proposed that TLR15 should be considered as a separate family. Indeed, TLR15 appears to have evolved independently from other TLR1 subfamily members ( 18 , 20 ), and shows structural differences such as an intact asparagine ladder and an ectodomain with single-domain architecture, instead of the three-domain architecture shared by all TLR1 family members ( 3 , 6 ).…”