Tuesday, July 12, 2022

What Have We Become


It appears that we could be evolving to better tolerate each other's body odor by having our noses become less sensitive to that smell over time. And the guy in the picture above has been "evolved" to withstand a car crash.

Humans and other primates have evolved less sensitive noses
Feb 2022, phys.org

The purpose of this study was to see if the genetics for smell remain constant across people from different backgrounds other than the Caucasians typically studied. 

The results showed that yes, they do, but also something unexpected.

"People with the ancestral versions of the scent receptors tend to rate the corresponding odor as more intense." And in opposition, the "newer" versions of those receptors lead to people having less intense odor detection capacity. And this suggests that we are evolving to be less sensitive to odors. 

In order to test their hypothesis, they used odors that were already known to be variable in the ways people perceive them. For example, some smells are very intense to some people but barely perceptible to others. Some of this is because of genetic variations in the way the receptor works. 

An interesting aside in the discussion -- "OR51B2 variation drives differences in the perception of human body odor component 3-methyl-2-hexenoic acid (3M2H) ... which could be a target for future studies interested in malodor blocking, or discovering the mechanisms underlying social communication from body odor."

Back to the big part of this study, which is the unexpected part (always the favorite part of any scientific endeavor). They measured the "age" of these genes, and found that the "newer" genes were less sensitive to intensity, and refer to this as "Degeneration of olfactory receptor gene repertoires in primates."

Image credit: Graham is designed to survive a car crash, Victoria’s Transport Accident Commission, 2016. Designed by Melbourne sculptor Patricia Piccinini, Royal Melbourne hospital trauma surgeon Christian Kenfield, and crash investigator at Monash University’s accident research centre David Logan.

Bonus:
Large genetic databases can be used to understand OR function, a proxy for general protein function.

In the discovery study, we may have the benefit of measuring olfactory phenotypes in a large, homogenous cohort (Fig 1) where genome-wide genotyping had already been conducted, giving us the statistical power of a large population without the time or expense. In this study, the novel signals do not have much population differences in MAF or effect size (Table 1 and Figs 3 and 4), suggesting that the large sample size rather than its genetic similarity might be the more important reason behind the findings. Given the increasing number of open databases of sequencing data, this method is becoming a more reasonable possibility for easily testing genotype/phenotype associations.

Olfaction is an excellent use of this new resource because of the ease of understanding the functional output of genetic variation in the protein. 
The human olfactory system has both robust assays to test the behavioral output of these proteins (psychophysics/rating odors) [5,6,10] and an established method for directly testing protein function in cells (heterologous cell-based assay) [42,43]. Genetic variation provides a strong tool for exploring olfactory coding and sheds light on how complex systems integrate information from variable sensors.

via Chinese Academy of Sciences Key Laboratory of Computational Biology at Shanghai Institute of Nutrition and Health, Monell Chemical Senses Center, Department of Neuroscience at University of Pennsylvania, and Sanghani Center for Artificial Intelligence and Data Analytics at Virginia Tech:  Li B, Kamarck ML, Peng Q, Lim F-L, Keller A, Smeets MAM, et al. (2022) From musk to body odor: Decoding olfaction through genetic variation. PLoS Genet 18(1): e1009564. doi.org/10.1371/journal.pgen.1009564

Some interesting facts about the variation of olfactory perception among populations, most of which was already known, but now confirmed for a more diverse population that includes Han Chinese:
  • Galaxide, a Musk molecule: Individuals can have specific anosmias to one or some, but not all musks, suggesting that there is not a single common coding mechanism.
  • Trans-3-methyl-2-hexenoic acid (3M2H), a Body Odor molecule: Almost 25% of the population has a specific anosmia to 3M2H [23–26], but this anosmia has not been connected to any olfactory receptor.
  • Aldehydes: Self-reported Asian populations rate aldehydes as more intense than Caucasian populations, but no specific genetic variants or receptors have been implicated. 

These are the receptors studied and their effects:
  • OR4D6 M263T and S151T ^ Galaxolide intensity
  • OR51B2 L134F ^ 3M2H intensity
  • OR5A1 D183N ^ β-ionone pleasantness (for the validation cohort and the meta-analysis, but not the discovery cohort)
  • OR7D4 R88W and T133M ^ Androstenone intensity and pleasantness (in the discovery cohort, for the validation cohort, only pleasantness)
  • OR2J3 T113A ^ Cis-3-hexen-1-ol intensity
  • OR1A1 =/= Caproic acid (although rs17762735 was associated with intensity in the validation study, the effect was in the opposite direction from the literature; there were no associations for 
  • pleasantness)
  • Aldehyde - There were no associations with aldehyde intensity or pleasantness 

On Body Odor:
3-methyl-2-hexenoic acid (3M2H) is also referred to as caproic acid, and as having a "hircine" odor, both of which refer to goats, because it smells like goats. Which means you smell like goats when you're hot and nervous and not wearing deodorant (although less likely if you're of Asian descent for whom one gene changes the production of body odor). Body odor in general is often characterized by thiolalcohols, which have sulfur molecules in them, although this one in particular doesn't have any sulfur in it. 

Related Post:
Social Deodorization

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