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Pacific rockfish give clues about the genetic basis of longevity

The name “rockfish” is applied to a wide variety of different groups of fish that typically live amongst rocks on the ocean floor. Rockfish from one particular genus (Sebastes) have recently been studied by scientists from UC Berkley, to investigate the genetic basis of their unusual longevity.

Tissue samples from 88 of the 137 species of rockfish in this genus, all known to inhabit coastal waters around the Pacific Ocean, were used to obtain DNA for analysis. 

The Sebastes group of fishes has undergone a very rapid evolutionary radiation in the past 10 million years, and has adapted to a wide range of different conditions and habitats. As a consequence, their phenotypes (i.e., their observable characteristics) differ widely in terms of their sizes, lifestyles, ecological niches, and longevity.  

Some species, such as the colorful calico rockfish (Sebastes dallii), live for little more than a decade. The most long-lived of the genus Sebastes – the rougheye rockfish (Sebastes aleutianus), which occurs from Japan to the Aleutian Islands – can survive in cold, deep coastal waters for more than 200 years. Some of the most long-lived vertebrate species on Earth are found in this genus. 

The researchers sequenced the complete genomes of the 88 rockfish species using a state-of-the-art technique known as Pacbio, or SMRT, sequencing. In particular, they were looking for DNA variations that were more common in fish with longer lives. 

The results show that a variety of genes are associated with a longer lifespan; they found a total of 137 longevity-associated gene variations. Although the researchers were aware that factors such as body size and habitat depth influence lifespan, they also identified several new genes that are involved with the process of ageing. 

Approximately 60 percent of variation in longevity was explained by variations in body size and the depth at which the species occur. Vertebrates with larger bodies usually live for longer (think of an elephant and a mouse, for example) and the fish that habitually live in deep, cold waters have a lower metabolic rate which is also associated with living for longer. 

“We can explain 60% of the variation in lifespan just by looking at the size at maturity and the depth at which a fish lives,” said senior author Professor Peter Sudmant. “So, you can predict lifespan with pretty high accuracy just from these factors. This allowed us to identify the genes that allow them to do those things.”

The remainder of the longevity-associated variation was explained mostly by differences in three types of genes: an enrichment in the number of genes for repairing DNA; variations in many genes that regulate insulin, which has long been known to influence lifespan; and an enrichment in genes that modulate the immune system. More DNA repair genes could help protect against cancer, while more immune genes could help ward off infections, as well as cancer.

“Six different members of the insulin signaling pathway are under selection in these fish,” said Professor Sudmant. “If you look at the textbooks, there are about nine or 10 core members of the pathway, so the majority of them are under selection in rockfish.”

Professor Sudamant explained that some rockfish species extended their lifespan simply by adapting to live in deeper, colder waters and increasing their size, but the longest-lived species boosted their lifespans even further by tweaking their DNA repair, insulin signaling and immune-modulation genes.

The scientists were also able to identify some consequences of a long lifespan in these rockfish. Species that live longer tend to have smaller populations (again, think of elephants and mice) and may survive today in small numbers that rely on very old, but very fertile, females to breed and restock the population. 

“In these rockfish, we can actually watch this evolution happening over this 10-million-year time period, and we observe that when some species evolve a short lifespan, their population sizes expand, and when they evolve a long lifespan, their population sizes contract,” said Professor Sudmant. “We can see a signature of that in their genomes, in the genetic variation that exists in these species. So, there is a consequence to adapting to long and short life.”

A fascinating finding from the study is that long-lived species have an excess of certain kinds of DNA mutations – specifically, the conversion of the nucleotide pair CG (cytosine-guanine) to TG (thymine-guanine) – that are known to accumulate in tumors with aging. Because it is the oldest females that produce most of the offspring in these long-lived species, these unusual genetic alterations are passed along to the rest of the long-lived population.

“In this study, we identified both the genetic causes and consequences of adaptation to extreme lifespan,” said Professor Sudmant. “It’s very exciting to be able to look at a group of species and see how their phenotype has been shaped through time and the genetic changes that drive that phenotype, and simultaneously, how that phenotype then feeds back and influences the genetic diversity of that population.”

The study may also help scientists understand human lifespan better. Sudmant and his colleagues found that longer-lived species had more immune modulating genes –  in particular, a group called butyrophilins – than shorter-lived species. The immune system is involved in regulating inflammation, and increased inflammation has been implicated in human aging. This implies that the findings of this study identify genes that could be used therapeutically to slow age-related damage in the body.

“There is an opportunity here to look in nature and see how natural adaptations have shaped lifespan and to think about how those same sorts of genes are acting in our own bodies,” explained Professor Sudamant.

The study is published in the journal Science.

By Alison Bosman, Staff Writer

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