A First Look at the Bowhead Whale Transcriptome

Numerous research groups are involved in comparative genetic analysis of aging and longevity: investigating the biology of unusually long-lived species in search of the reasons why these animals are unusually long-lived in comparison to their peer. We humans actually fall into this category, having a greater longevity than our nearest primate cousins. Nonetheless, there are much more exceptional species out there, even if we restrict ourselves to the study of mammals. Some whales can live for centuries, and naked mole rats live for nine times as long as other similarly sized rodents.

There is the hope that beyond new knowledge the investigation of long-lived species might point the way towards means of slowing aging or treating age-related disease in humans. That really depends on the details, however: it is entirely possible for a mechanism of longevity (or regeneration as in salamanders, or cancer resistance as in naked mole rats, and so forth) to in the end turn out to be clear, well-understood, and nonetheless in no way useful to human medicine. The more likely outcome is that it takes a very long time and a lot of money to come to even a preliminary understanding, and at the end of the day those resources might have better been spent on directly advancing human medicine. If you've been following research into salamander regeneration over the past decade, for example, you'll see what I mean. Perhaps there is a grail there, perhaps not, and we won't know without a great deal more research - and this at a time when purely human regenerative medicine is advancing by leaps and bounds.

Nonetheless, comparative studies of aging and longevity are underway, and like all such research these days the scientists involved are producing mountainous vaults of data. The Methuselah Foundation, for example, presently provides a modest grant to a UK research group to sequence the genome of bowhead whale. On the basis of various direct and indirect evidence individuals of this species are thought to live for more than two centuries, and it seems only reasonable to ask how the whales manage this feat. The UK group are not the only researchers to work on answering this question. Another group that has studied bowhead whales for some years has recently published their first pass at the bowhead whale genome:

The transcriptome of the bowhead whale Balaena mysticetus reveals adaptations of the longest-lived mammal

Mammals vary dramatically in lifespan, by at least two-orders of magnitude, but the molecular basis for this difference remains largely unknown. The bowhead whale Balaena mysticetus is the longest-lived mammal known, with an estimated maximal lifespan in excess of two hundred years. It is also one of the two largest animals and the most cold-adapted baleen whale species. Here, we report the first genome-wide gene expression analyses of the bowhead whale, based on the de novo assembly of its transcriptome.

The bowhead's lifespan far exceeds that of other renowned long-lived species of mammals studied for molecular insights into aging. However, limited access to tissues of these animals has precluded detailed analyses of biological functions based on gene expression. As a first step in identifying such patterns, we present the liver, kidney and heart transcriptomes of the bowhead whale. Comparison of the bowhead whale transcriptome with that of the related minke whale and other mammals enabled us to identify candidate genes for the exceptional longevity of the bowhead whale.

It has been proposed that the difference in longevity between humans and other primates stems from differential expression of a small number of genes. A recent study comparing humans to eight other mammals, including primates, revealed that 93 liver and 253 kidney genes showed evidence of human lineage-specific expression changes. The number of genes differentially expressed in the bowhead whale liver (45 genes) and kidney (53 genes) compared to other mammals is similar, albeit using a different computational method. We speculate that the genes differentially expressed, with unique coding sequence changes and rapidly evolving in the bowhead whale, represent candidate longevity-promoting genes. We particularly stress the findings suggestive of altered insulin signaling and adaptation to a lipid-rich diet. The availability of a single heart tissue sample from the bowhead whale precluded identification of distinct gene expression patterns in the long-lived bowhead whale, but revealed that argininosuccinate lyase (Asl) may protect the heart of cetaceans during hypoxic events such as diving.

This is just a starting point, and other research groups will add to it in the years ahead. It is interesting to speculate on the role of hypoxia in the evolution of longevity, for example, as both whales and naked mole rats experience frequent long exposure to oxygen-poor environments: diving for the whales, and life underground in poorly ventilated tunnels for the naked mole rats. In fact these are not the only species in which hypoxia is theorized to spur the evolution of longevity, not directly, but as a side-effect of the class of cellular mechanisms needed for a complex animal to thrive in oxygen-poor environments.

Comments

We came to the conclusion yeas ago when working on markers of carbonly stress pentosidine cml and glycoxidative stress that these animals did not have the same aging mechanism as other mammals. The levels of these markers demonstrated these animals had slow carbohydrate metabolism rates. Speculation included myoglobin, dietary differences etc. it wanted to continue the work but obtaining long lived lens tissues was next to impossible. Hypoxia protective mechanisms are very good candidates. I suggested better animals than The bow head there as well.

Posted by: Dr Obrenovich at November 9th, 2014 7:29 PM

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