Insights into the Evolution of Longevity from the Bowhead Whale Genome

Abstract

SummaryThe bowhead whale (Balaena mysticetus) is estimated to live over 200 years and is possibly the longest-living mammal. These animals should possess protective molecular adaptations relevant to age-related diseases, particularly cancer. Here, we report the sequencing and comparative analysis of the bowhead whale genome and two transcriptomes from different populations. Our analysis identifies genes under positive selection and bowhead-specific mutations in genes linked to cancer and aging. In addition, we identify gene gain and loss involving genes associated with DNA repair, cell-cycle regulation, cancer, and aging. Our results expand our understanding of the evolution of mammalian longevity and suggest possible players involved in adaptive genetic changes conferring cancer resistance. We also found potentially relevant changes in genes related to additional processes, including thermoregulation, sensory perception, dietary adaptations, and immune response. Our data are made available online (http://www.bowhead-whale.org) to facilitate research in this long-lived species.

Hypoxia potentially promotes Tibetan longevity

“…In addition, wild mammals with hypoxic habitats, such as the naked mole rat that lives in burrow, and whales that must hold their breath as they dive, seem to live longer [3][4][5]. In stark contrast with observations in the laboratory, humans living under natural hypoxic environment of the Tibetan Plateau have generally been thought to have much shorter lifespans compared with people living at lower altitudes.…”

“…On the other hand, hypoxia might induce longevity in Tibetans, as has been stated for model animals under laboratory experimentation [1,2], as well as wild mammals that live in natural hypoxic environments, such as the naked mole rat and whales [3][4][5]. Considering the strongly significant greater frequency of interaction between aging-associated genes and hypoxia response genes (Supplementary information, Figure S1F and Data S1), and the fact that 18 genes were shared between these two groups of genes, it is likely that hypoxia stress would accelerate the evolution of aging-associated genes.…”

“…This result suggests that genes downregulated during aging tend to be upregulated under hypoxia, and vice versa. Hypoxia, thus, might offset the effect of aging and therefore extend lifespan, as observed in model and wild animals [1][2][3][4][5].…”

The African turquoise killifish: A research organism to study vertebrate aging and diapause

“…While several evolutionary studies have focused on exceptionally long‐lived animals such as bowhead whale and naked mole rat, the turquoise killifish provides a new perspective from the other side of the lifespan spectrum (“life in the fast lane”; Keane et al., 2015; Reichwald et al., 2015; Valenzano et al., 2015). …”

Comparative oncology: what dogs and other species can teach us about humans with cancer

“…Bowhead whales, the longest living mammal with a lifespan of over 200 years and reportedly very low cancer rates, recently were described to harbour genomic alterations associated with cancer, ageing, cell cycle and DNA repair (e.g. ERCC1 and PCNA) [167]. Elephants represent another large mammal that appears to be protected from cancer [168,169], and various studies are underway to explain the molecular basis for this phenomenon known as Peto's paradox (large and long-lived animals that appear to be cancer resistant) [170][171][172][173][174][175].…”