Exploring the Greenland shark's secret to extreme longevity

Greenland sharks are thought to have lifespans that can reach 400 years. University of Tokyo-led researchers have now sequenced the first chromosome-level genome of the Greenland shark (Somniosus microcephalus), revealing genetic adaptations linked to its extraordinary lifespan, immune function, and deep-sea survival.

Greenland sharks inhabit the North Atlantic and Arctic Oceans, reaching lengths of over six meters and weights exceeding 1,400 kilograms. A growth rate of approximately one centimeter per year suggests an extended lifespan, confirmed by radiocarbon dating of the eye lens, which estimated one individual to be about 400 years old.

Existing genomic studies on other long-lived species, including elephants and rockfish, have identified specific gene variations associated with extended lifespans. Yet, no genomic research had been conducted on the Greenland shark before this study.

Large genome sizes, technical challenges in sequencing, and limited conservation data have hindered a full understanding of Greenland shark biology. Research efforts have been constrained by difficulties in obtaining high-quality genomic material. A comprehensive genome sequence could provide insight into the species' exceptional longevity, cancer resistance, and environmental adaptations.

In the study titled "The Greenland Shark Genome: Insights into Deep-Sea Ecology and Lifespan Extremes," published as a preprint on bioRxiv, researchers conducted whole-genome sequencing to investigate genetic factors linked to longevity and deep-sea adaptation.

A female Greenland shark was captured in Kongsfjorden, Svalbard Archipelago, as part of an ongoing biotelemetry study. Tissue samples (fin clips and blood) were taken before the shark was released back into the wild.

High-fidelity long-read genome sequencing was performed on the samples, yielding approximately 34.5x coverage of the genome. A chromosome-scale genome assembly was constructed using Hi-C sequencing data, resulting in a 5.9-gigabase genome with an N50 scaffold length of 233 megabases. A total of 37,125 protein-coding genes were annotated, achieving a completeness score of 86.5%.

Comparative analyses identified 549 expanded and 1,461 contracted gene families. Among the expanded families, genes involved in NF-κB signaling, DNA repair, and immune function showed significant increases. The TNF, TLR, and LRRFIP gene families, all of which regulate NF-κB signaling, exhibited a higher copy number compared to shorter-lived shark species. NF-κB plays a crucial role in cellular protection, inflammatory response, and apoptosis, suggesting a genetic foundation for prolonged lifespan and disease resistance.

Several genes known to influence cancer suppression, including FOXF2, FSCN1, and MAD2L1BP, showed signs of positive selection. FOXF2 regulates the tumor immune microenvironment, while FSCN1 influences cell migration and tumor progression. MAD2L1BP is involved in chromosome stability and DNA repair, key processes in cancer resistance.

Greenland sharks live at extreme depths with minimal light exposure. A rhodopsin gene (RHO) variant in this species displayed amino acid substitutions consistent with a spectral shift toward blue light, a characteristic adaptation to deep-sea environments. Comparisons with other chondrichthyan species confirmed similarities with known deep-sea dwellers, indicating genetic adaptations for dim-light vision.

Field observations of the captured shark showed that Greenland sharks responded to submersible lights underwater and to nearby movements while on deck, challenging previous assumptions about their poor vision due to corneal parasites.

Researchers analyzed population genetics between Greenland sharks and their closest relatives, Pacific sleeper sharks (Somniosus pacificus). Genomic data suggested a long-term decline in effective population size for Greenland sharks, whereas Pacific sleeper sharks experienced a historical bottleneck followed by signs of population recovery.

Divergence estimates revealed two genetic separation signals: an earlier divergence around 10 million years ago and a more recent genetic isolation event approximately 3 million years ago. Additionally, analysis of runs of homozygosity suggests that Greenland sharks may have undergone recent inbreeding, while Pacific sleeper sharks exhibit evidence of past inbreeding followed by population expansion.

Runs of homozygosity analysis suggested higher inbreeding in Greenland sharks compared to Pacific sleeper sharks, while heterozygosity analysis indicated a long-term effective population size approximately 1.5 times greater in Greenland sharks than their relatives.

Sequencing data revealed multiple genetic mechanisms potentially linked to longevity, cancer resistance, and immune regulation. Expansions in NF-κB-related genes, along with positively selected cancer-related genes, suggest evolutionary adaptations that contribute to its extended lifespan and disease resilience. A spectral tuning adaptation in rhodopsin indicates a visual system optimized for deep-sea conditions.

Greenland sharks reach maturity at approximately 150 years, making them extremely vulnerable to overfishing and environmental changes. The study provides a foundational genomic resource for understanding population dynamics, evolutionary history, and potential conservation strategies for this long-lived species.

The findings also indicate a strong association between specific gene families and longevity, immune response, and cancer resistance, providing a foundation for future human aging studies.

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