Tuesday , December 18 2018

Giant Tortoise Genomes Provide Insights into Gigantism, Longevity and Age-Related Disease

A team of researchers from Yale University, the University of Oviedo in Spain, the Galapagos Conservancy, and the Galapagos National Park Service has sequenced and analyzed the genomes of Lonesome George — the iconic last member of the Pinta Island tortoise (Chelonoidis abingdonii) — and the Aldabra giant tortoise (Aldabrachelys gigantea), and identified new candidate genes and pathways that may underlie the extraordinary characteristics of these iconic species, including their development, gigantism and longevity.

Chelonoidis abingdonii. Image credit: Quesada et al, doi: 10.1038/s41559-018-0733-x.

Chelonoidis abingdonii. Image credit: Quesada et al, doi: 10.1038/s41559-018-0733-x.

Giant tortoises are among the longest-lived vertebrate animals and, as such, provide an excellent model to study traits like longevity and age-related diseases.

However, genomic and molecular evolutionary information on these tortoises is scarce.

To obtain such data, Yale University researcher Adalgisa ‘Gisella’ Caccone and co-authors conducted genetic analysis of DNA from two long-lived giant tortoises: Lonesome George — the last representative of Chelonoidis abingdonii, endemic to the island of Pinta (Galapagos islands, Ecuador) — and an individual of Aldabrachelys gigantea, endemic to the Aldabra Atoll and the only extant species of giant tortoises in the Indian Ocean.

“Lonesome George is still teaching us lessons,” Dr. Caccone said.

“In 2010, I began sequencing the whole genome of Lonesome George to study evolution of the tortoise population on the Galapagos.”

“University of Oviedo’s Dr. Carlos Lopez-Otin analyzed these data and other species of tortoises to look for gene variants associated with longevity.”

Genomic basis of longevity and cancer in giant tortoises: (a) genes potentially implicated in Chelonoidis abingdonii and Aldabrachelys gigan longevity extension and cancer resistance, classified according to their putative role in the different hallmarks; tables indicate copy-number variations and relevant variants of age-related genes and tumor suppressors found in Chelonoidis abingdonii, Aldabrachelys gigan and other species; within these tables, numbers indicate gene copy numbers, and asterisks represent pseudogenization events; dots in colors relating to each hallmark represent presence of the variant; (b) Venn diagrams showing the relationships between cancer-, aging- and immunity-related genes, as classified before annotation; top - all of the genes related to each category that have been manually annotated, including the number of genes in each group; bottom - those genes showing potentially interesting variations after annotation. Image credit: Quesada et al, doi: 10.1038/s41559-018-0733-x.

Genomic basis of longevity and cancer in giant tortoises: (a) genes potentially implicated in Chelonoidis abingdonii and Aldabrachelys gigan longevity extension and cancer resistance, classified according to their putative role in the different hallmarks; tables indicate copy-number variations and relevant variants of age-related genes and tumor suppressors found in Chelonoidis abingdonii, Aldabrachelys gigan and other species; within these tables, numbers indicate gene copy numbers, and asterisks represent pseudogenization events; dots in colors relating to each hallmark represent presence of the variant; (b) Venn diagrams showing the relationships between cancer-, aging- and immunity-related genes, as classified before annotation; top – all of the genes related to each category that have been manually annotated, including the number of genes in each group; bottom – those genes showing potentially interesting variations after annotation. Image credit: Quesada et al, doi: 10.1038/s41559-018-0733-x.

The researchers found that the giant tortoises possessed a number of gene variants linked to DNA repair, immune response, and cancer suppression not possessed by shorter-lived vertebrates.

“We had previously described nine hallmarks of aging, and after studying 500 genes on the basis of this classification, we found interesting variants potentially affecting six of those hallmarks in giant tortoises, opening new lines for aging research,” Dr. Lopez-Otin said.

The findings appear in the journal Nature Ecology Evolution.

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Víctor Quesada et al. Giant tortoise genomes provide insights into longevity and age-related disease. Nature Ecology Evolution, published online December 3, 2018; doi: 10.1038/s41559-018-0733-x

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