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Sequencing Study Uncovers Genes Under Positive Selection in Large, Long-Lived Sea Creatures

NEW YORK – A Brazilian research team has tracked down a handful of genes that appeared to contribute to "gigantism" in a subset of cetaceans such as the blue whale (Balaenoptera musculus), fin whale (B. physalus), or sperm whale (Physeter catodon), including genes suspected of protecting the large, long-lived sea creatures from the increased cancer risk expected to accompany a jump in size.

"Our results suggest the action of positive selection on gigantism in genes that act both in body augmentation and in mitigating its consequences, such as cancer suppression when involved in processes such as division, migration, and cell development control," senior and corresponding author Mariana Nery, a genomic evolution researcher at the State University of Campinas (UNICAMP), and her colleagues wrote.

For a paper published in Scientific Reports on Thursday, the researchers brought together available sequence data for 19 species of cetaceans, a group that encompasses dolphins, porpoises, and whales. From these sequences — which represented seven giant cetacean and a dozen non-giant cetacean species — they focused in on a handful of genes from growth hormone/insulin-like growth factor pathways or genes previously linked to size in other cetacean-related species, including pigs, cows, and sheep.

In particular, the team saw positive selection in the growth hormone/insulin-like growth factor genes GHSR and IGFBP7 and in PLAG1 and NCAPG. Those genes have been implicated in prenatal growth and body size in cattle, while IGFBP7 has been shown to have additional ties to cancer suppression in past research.

"[I]t seems that IGFBP7 is related to two main characteristics of giant cetaceans' increase in body size and suppression of cancer," the authors wrote, noting that "cancer suppressor genes have already been reported to be under positive selection for cetaceans, and IGFBP7 is likely to be one more."

In a paper published in Current Biology early last year, the National Human Genome Research Institute's Elaine Ostrander and colleagues delved into another insulin-like growth factor locus housing IGF1, which has been implicated in the highly variable body sizes found in domestic dogs.

There, they demonstrated that a derived variant in an antisense long-coding RNA that interacts with IGF1 is linked to body size in large dog breeds and modern gray wolves, while an ancient ancestral variant linked to smaller stature has been subject to selection during the development of small dog breeds.

When it came to the toothless cetacean species from the Mysticeti suborder, meanwhile, the Brazilian researchers unearthed ties to the pseudogenization of an epidermal growth factor-coding gene, EGF, stemming from a premature stop codon.

"[W]e found evidence of pseudogenization of the EGF gene in the Mysticeti lineage, an event likely related to teeth loss in these cetaceans, which could be connected with the emergence of the baleen plate filter system," the authors wrote.

Together, they suggested, the study's findings offer "new perspectives on the evolution of cetacean gigantism, reinforcing the selective pressures of the aquatic environment, the various possibilities of action of natural selection on different genes that have similar functions depending on specific characteristics for each species, and indicating that pseudogenization is also an adaptive process for this group."

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