Gene Duplication and the Evolution of Longevity in Mammals

Researchers here use some of the more recently sequenced mammalian genomes, of the majority eutherian branch that encompasses all of the mammals you might be familiar with, to investigate a potential role for gene duplication in the evolution of aging and longevity. This is a good example of much of the breadth of research into aging in that it is very far removed from any practical outcome: it is an unhurried process of mapping. Fundamental research is nonetheless essential despite - or arguably because of - the lack of a clear use for the knowledge gained.

One of the greatest unresolved questions in aging biology is determining the genetic basis of interspecies longevity variation. Within Eutherians, bowhead whales live more than 200 years, while short-lived rodents generally live up to 4 years. Gene duplication is often the key to understanding the origin and evolution of important Eutherian phenotypes. Many longevity-associated pathways evolved via gene duplication, and duplication can increase lifespan and impact the pathogenesis of various aging-related diseases. With the availability of genomes from long- and short-lived species and a set of hundreds of genes known to influence lifespan in model organisms, we thoroughly investigated the role that gene duplication played in the evolution of Eutherian longevity from a systematic perspective.

Longevity-associated gene families have a marginally significantly higher rate of duplication compared to non-longevity-associated gene families. Anti-longevity-associated gene families have significantly increased rate of duplication compared to pro-longevity gene families and are enriched in neurodegenerative disease categories. Conversely, duplicated pro-longevity-associated gene families are enriched in cell cycle genes. There is a cluster of longevity-associated gene families that expanded solely in long-lived species that is significantly enriched in pathways relating to 3-UTR-mediated translational regulation, metabolism of proteins and gene expression, pathways that have the potential to affect longevity. The identification of a gene cluster that duplicated solely in long-lived species involved in such fundamental processes provides a promising avenue for further exploration of Eutherian longevity evolution.

We can only speculate whether the inferred duplication patterns in this study could have impacted Eutherian longevity. In reality, longevity evolution is probably the result of many genes exhibiting small effect sizes, meaning that pinpointing the exact source of longevity determination will be extremely difficult to detect, even in large studies. Because we know that the environment and condition of an individual play a massive role on the proteins that are being expressed, perhaps the true meaning of the reason for duplicating these genes in long-lived species may not be fully understood from solely this perspective. However, subtle differences at the genomic level can exert a large phenotypic effect. It is possible that duplicating a small cluster of interrelated genes solely in long-lived species that have core functions involved in RNA and protein metabolism could have directly or indirectly impacted their longevity through their functions in gene and protein networks.



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