Comparative genomics of longevity

Some rockfish live over two-hundred years. Some gobies only live sixty days. Humans live roughly eighty-five years. How is this variation regulated, and can these differences inform treatments to delay aging in people? These are defining, heritable traits for species, and the mechanisms underlying the dramatic variation across species must be present in their genomes.

Evolution of Exceptional Longevity in Rockfish and Humans

Using rockfish evolution as a filter, we identify shared signatures underlying longevity in humans.

To resolve the genetic regulation of longevity, we have mined genomic variation in rockfishes, ranging in maximum lifespan from 11 to over 205 years. Multiple shifts in rockfish longevity have occurred independently, and in a short evolutionary time frame, thus empowering convergence analyses. Our analyses reveal a common network of genes under convergent restricted evolution in long-lived lineages, encompassing established aging regulators such as insulin-signaling, yet also identify flavonoid (aryl-hydrocarbon) metabolism as a novel pathway modulating longevity. Further, these genes were used to refine human longevity GWAS, identifying the aryl-hydrocarbon metabolism pathway to be significantly associated with human survival to the 99th percentile. This evolutionary intersection defines and cross-validates a novel, conserved genetic architecture that associates with the evolution of longevity across vertebrates.

Evolution of Fleeting Lifespan in Dwarf Gobies

Dwarf Goby. Very small. Very cute. Very short-lived.

An extreme example of the evolution of shortened longevity is evident in small coral reef gobies of the genus Eviota. In response to high levels of extrinsic mortality, these Goby species evolved extremely rapid life cycles. The whole species group is characterized by short lifespans of about 100 days with documented extremes of less than 50 days. Outside the genus, other gobies have evolved a diversity of lifespans, up to twelve years. With collaborators at the Unversity of Washington, we have sampled and sequenced the “conservome” of 24 goby lineages, including 12 in the Eviota genus. This is a rich resource to unravel the evolution of dwarf gobies and perform comparative genomics within Gobies, as well as empower meta-analyses across teleosts.

Population Genetics of the World’s Longest Lived Animal Species

Arctica islandica. Maximum lifespan: 507 years. Great in chowder.

The ocean quahog, Arctica islandica, can survive for over five-hundred years off the coast of Iceland. However, 1000 miles away in the Baltic sea, they survive for only 35 years. With collaborators from the Alfred Wegener Institute, we have generated a high quality reference genome for Arctica islandica and sequenced individuals from the different populations. We are working to identify genomic controls that may be underlying the dramatic reduction in maximum longevity as the species proliferated into the Baltic sea roughly 10,000 years ago.

Key Publications

• Treaster S., Deelen J., Daane J., Murabito J., Karasik K., Harris MP. (2023) Convergent genomics of longevity in rockfishes highlights the genetics of human life span variation. Science Advances 2023 Jan 11;9(2):eadd2743[link]
  • Highlighted in:
    • The Scientist: Rockfish Genes Hold Clues to Human Longevity.
    • Popular Science: What rockfish genes can teach humans about living past 100.
    • Germany National Public Radio
    • Austria National Public Radio
• Treaster S., Karasik, D., and Harris, MP. (2021) Footprints in the Sand: Deep Taxonomic Comparisons in Vertebrate Genomics to Unveil the Genetic Programs of Human Longevity. Front. Genet. 12.[link]

Funding

National Academy of Medicine Healthy Longevity QuickFire Accelerator Award
National Academy of Medicine Healthy Longevity QuickFire Catalyst Award
Harvard Medical School Genetics Climate Change Fellowship
Glenn/AFAR Postdoctoral Fellowship in Aging Research