The whale shark genome reveals patterns of vertebrate gene family evolution

Abstract

Due to their key phylogenetic position, cartilaginous fishes, which includes the largest fish species Rhincodon typus (whale shark), are an important vertebrate lineage for understanding the origin and evolution of vertebrates. However, until recently, this lineage has been understudied in vertebrate genomics. Using newly-generated long read sequences, we produced the best gapless cartilaginous fish genome assembly to date. The assembly has fewer missing ancestral genes than Callorhinchus milii , which has been widely-used for evolutionary studies up to now. We used the new assembly to study the evolution of gene families in the whale shark and other vertebrates, focusing on historical patterns of gene family origins and loss across early vertebrate evolution, innate immune receptor repertoire evolution, and dynamics of gene family evolution size in relation to gigantism. From inferring the pattern of origin of gene families across the most recent common ancestors of major vertebrate clades, we found that there were many shared gene families between the whale shark and bony vertebrates that were present in the most recent common ancestor of jawed vertebrates, with a large increase in novel genes at the origin of jawed vertebrates independent of whole genome duplication events. The innate immune system in the whale shark, which consisted of diverse pathogen recognition receptors (PRRs) including NOD-like receptors, RIG-like receptors, and Toll-like receptors. We discovered a unique complement of Toll-like receptors and triplication of NOD1 in the whale shark genome. Further, we found diverse patterns of gene family evolution between PRRs within vertebrates demonstrating that the origin of adaptive immunity in jawed vertebrates is more complicated than simply replacing the need for a vast repertoire of germline encoded PRRs. We then studied rates of amino acid substitution and gene family size evolution across origins of vertebrate gigantism. While we found that cartilaginous fishes and giant vertebrates tended to have slower substitution rates than the background rate in vertebrates, the whale shark genome substitution rate was not significantly slower than Callorhinchus . Furthermore, rates of gene family size evolution varied among giants and the background, suggesting that differences in rate of substitution and gene family size evolution relative to gigantism are decoupled. We found that the gene families that have shifted in duplication rate in whale shark are enriched for genes related to driving cancer in humans, consistent with studies in other giant vertebrates than support the hypothesis that evolution of increased body size requires adaptations that result in reduction of per cell cancer rate.Performance Computing oversight committee for access and assistance with the Center for Advanced Science Innovation and Commerce (CASIC) supercomputer at Auburn University, the rest of the staff of Laboratory of Phyloinformatics in RIKEN BDR for transcriptome sequencing, and R. A. Petit III for assistance with comp...

Visual and nonvisual opsin genes of sharks and other nonosteichthyan vertebrates: Genomic exploration of underwater photoreception

“…Later, in the other subclass Elasmobranchii, genome sequence information of two orectolobiform shark species (brownbanded bamboo shark Chiloscyllium punctatum and whale shark Rhincodon typus), one lamniform species (white shark Carcharodon carcharias) and one carcharhiniform species (cloudy catshark Scyliorhinus torazame) became available (Hara, Yamaguchi, et al, 2018;Marra et al, 2019;Read et al, 2017;Tan et al, 2019), which ascertained the consistent absence of SWS1 and SWS2 in these shark species (Figure 1).…”

Evolution of Matrix Gla and Bone Gla Protein Genes in Jawed Vertebrates

“…Additional cDNA sequences were obtained by screening accessible transcriptomic data collected by the SkateBase project 1 [little skate Leucoraja erinacea transcriptome (Contig Build-2, GEO:GSM643957) and small-spotted catshark transcriptome (GEO:GSM643958)] using TBLASTN. Small-spotted catshark, little skate, and thornback ray sequences were then used to screen other databases for elephant shark genome assembly (GCA_000165045.2 Callorhinchus_milii-6.1.3) ( Venkatesh et al, 2014 ) and whale shark genome Rhincodon typus (GCA_001642345.2 ASM164234v2) ( Tan et al, 2019 ). Thornback ray, small-spotted catshark, and little skate cDNA sequences were used to map synteny on the thorny skate Amblyraja radiata and the smalltooth sawfish Pristis pectinata draft assembled genomes using TBLASTN [data accessed from, and analyzed in agreement with, Vertebrate Genome Project ( Rhie et al, 2020 ), PriPec2.pri, GCA_009764475.1].…”

Immunological Diversity Is a Cornerstone of Organismal Defense and Allorecognition across Metazoa

“…Relative to mammals, teleost fish genomes also exhibit considerable expansions within the gene families encoding NLR (15) and TRIM ( 16) proteins. In contrast, RLR repertoires are highly conserved across vertebrates (14).…”

“…13). Analysis of these sequences suggests that the ancestor of jawed vertebrates possessed a much larger TLR repertoire (19 genes) than most modern species (14). In addition, data suggest that the TLR repertoires within the extant jawed vertebrates are the result of lineage-specific diversification, differential gene loss, and gene duplication events.…”

“…For example, although TLR4 orthologs are present in many bony fish and amphibians, these lineages are not particularly sensitive to Escherichia coliderived LPS, which is the primary ligand for mammalian TLR4 (22). Instead, the TLR4-LPS signaling network appears to have evolved only after the divergence of amphibians (13,14). Likewise, a recent study demonstrated that, despite broad structural similarities, LPS isolated from deep-sea, Gram-negative g-proteobacteria were poor stimulators of the LPS-sensing PRRs from mice and humans (23).…”