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#longevity

waynerad@pluspora.com
Wayne Radinsky

"Comparative genomic study, the largest to date, includes genetic and phenotypic information of 57 species of mammals and identifies the greater stability of proteins as a common feature in the longest-living species".

So this research is all about convergent amino acid substitutions, and I had to do some work to understand what convergent amino acid substitutions are about. Basically, you can have a mutation in DNA, and that mutation, even if it is just a change to a single nucleotide, can change one of the amino acids in the protein the DNA encodes for. This change is what the word "substitution" refers to. The change can have no effect on the function of the protein, if the change is located somewhere that isn't related to the key parts that control the function of the protein. It also might have little effect, even if it is in one of the key parts, if the new amino acid is similar enough to the old one. It is also possible, however, for the change to have a very radical effect on the function of the protein.

The "convergent" part of that phrase has to do with the concept of convergent evolution. Convergent evolution is when two unrelated species evolve the same trait. For example, wings evolved in reptiles to form birds, and independently in mammals to form bats.

But the headline tells you this is about lifespan, so the question then becomes what all this has to do with longevity? Well, the way this research was structured was to find convergent amino acid substitutions in a variety of species, and compare those with the lifespan, and see which of those have longer or shorter lifespans than expected. This is different from previous genome-wide association studies (GWAS) that have focused on humans only.

They found 2,737 convergent amino acid substitutions in 2,004 genes where long-lived species have one amino acid and short-lived species have another. They further narrowed this down to 996 genes that they believe represent "true longevity signals" using statistical tests ("phylogenetic ANOVA test", whatever that is). The research paper has a lot of complex statistics that I didn't understand and can't summarize for you.

You may be wondering what the amino acid changes do? They think that they increase protein "stability", which is to say, proteins tend to "destabilize" with age and the convergent evolution of certain amino acid choices in long-lived species lead to those species having proteins that better resist this "destabilization".

They speculate what leads to this increased "stabilization" is "contacts in the hydrophobic core" and "a reduction in Van der Waals clashes".

The idea behind the "hydrophobic core" theory is that a protein will maintain a stable structure by constructing a shape such that there is a "center" created by a group of highly hydrophobic amino acids -- hydrophobic means they don't like water. Hydrophillic -- water-loving -- amino acids will be on the outside and will perform the function of the protein. Mutations that increase the stability of this "hydrophobic core" would, then, increase longevity, while mutations that decrease the stability of the "hydrophobic core" would decrease longevity.

Unfortunately I don't understand Van der Waals forces well enough to explain what "Van der Waals clashes" are. Van der Waals forces are forces that arise from quantum fluctuations in electron shells that result in fluctuating positive or negative electric forces that result in attraction or repulsion between parts of molecules that are very close to each other. They play a central role in organic chemistry, so I should probably learn about them.

The evolution of mammals reveals 2,000 new genes key to longevity in humans

#discoveries #evolution #proteome #genomics #gwas #longevity

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