Use It Or Lose It

I've long been fond of the quip, “Use it or lose it.” It’s served to boost my motivation on many occasions.  If you Google the phrase, the first hit is about erections, then one about the brain, then one on physical exercise.  The idea is that both physical and mental skills need to be honed or they atrophy.

The phrase also applies to genetic information.

Genes and their regulatory elements are under steady mutational pressure: While the enzymes that copy genomes for transmission to the next generation are impressively accurate, they occasionally make errors, and environmental mutagens occasionally alter genetic sequences as well.  If a gene/element is essential for the organism to survive-to-reproduce, and if the mutant version disallows survival-to-reproduction, then the mutant version is quickly eliminated from the gene pool by natural selection.

There’s also a second and more interesting scenario called masking. 1) A species is genetically “hard-wired” to carry out some function necessary to its lifestyle. 2) The function becomes available to the species from an outside source. 3) In this case, any mutations that compromise the hard-wired program are masked from selection because the outside source “covers” the function. 4) Over time, therefore, the hard-wired program tends to degrade, but in this case the mutant versions of the genes/elements are not immediately eliminated from the gene pool. Instead, they drift along, accumulating additional mutations until they only partially resemble their original sequences (at which stage they are called pseudogenes). Eventually they become fully unrecognizable, joining the vast majority of genomic DNA that’s called “junk.” Because they are no longer necessary — no longer used, no longer under selection — they wander and stumble towards elimination.

A straightforward example of masking in the human lineage relates to a gene encoding the enzyme L-gulonolactone oxidase (GULO), a component of the pathway leading to the synthesis of ascorbic acid. Ascorbic acid is an essential cofactor for several metabolic and biosynthetic processes, including the synthesis of collagen, and in most plants and animals, mutations that disable GULO function are lethal and the mutant gene is quickly eliminated from the gene pool. However, in our primate lineage, fruit became a major food source. Fruit is rich in ascorbic acid. Therefore, mutations in the GULO gene were masked from natural selection because the endogenous synthesis of ascorbic acid was no longer necessary – we were already ascorbic-acid replete. As a consequence, GULO is now a chimp/human pseudogene, and exogenous ascorbic acid has become a requirement. We call it vitamin C.

A second example relates to the vomeronasal organ (VNO). We share common ancestry with rodents and shrews, and in these animals, urinary pheromones bind to receptors in a region of the brain called the VNO where they mediate gender discrimination during mating. In gorillas, chimps, and humans, the VNO starts to form during fetal development but then degrades, indicating that reliance on other sexual cues has masked selection to maintain a functional VNO system.

A dramatic example of use-it-or-lose-it occurs during the evolution of parasitism. As organisms in a free-living lineage develop a parasitic relationship with a host organism, thereby acquiring the products of entire metabolic pathways from an exogenous source, the genes encoding these metabolic pathways degrade in the evolving parasite. As a consequence, the genomes of established parasites may contain only half the genes of their free-living cousins.

The masking scenario has been offered as one way to think about the evolution of human minds. In an earlier blog on finches, I describe how selection to maintain a song recognizable by female mates has been effectively masked when finches are instead artificially bred on the basis of their plumage: the guy no longer needs to sing accurately to get the girl, so the hard-wired program degrades and he instead sings any old song, including an improv learned from another male.

In like fashion, it has been suggested that once language-based culture started providing hominids with useful information from the outside, hard-wired programs (“instincts”) specifying redundant or conflicting information systems in the brain were masked from selection by cultural information, and the instincts became vulnerable to degradation.

An interesting consequence of the masking phenomenon is addiction. The parasite is addicted to its host, and we humans are now addicted to vitamin C, to non-pheromonal sexual cues, and to cultural information. When you lose muscle strength by inactivity, you have the option to restore it by exercise; when you lose genetic instructions by masking, you’re stuck with an external addiction.

This doesn’t mean, of course, that we’re stuck with the cultures we have. For better or worse, cultures are stunningly evolvable, capable of changing in far more rapid time frames than instincts.  Perhaps the key project of our times is to figure out how to acquire a global addiction to cultural premises that are in keeping with global sustainability. Without same, we appear fated to a tragic trajectory towards extinction.



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