Saturday, October 30, 2021

Genetics and Non-Genetics of Temperament

Some fish are shy, some honeybees are outgoing. What makes individuals out of a uniform genetic background?

Do flies have personalities? Apparently so. Drosophila have a long and storied history as perhaps the greatest model organism for genetic research. They have brains, intricate development, complex bodies and behaviors, but also rapid generation time, relatively easy handling, and mass rearing. A new paper describes a quest to define their personalities- behavioral traits that vary despite a uniform genetic background. Personality is a trait that may be genetically influenced, but may just as well have environmental or sporadic causes (that is, not determined by outside factors). Importantly, this kind of trait tends to recur in a population, indicating that while it may not be determined, it follows certain canalized pathways in development, which might themselves be amenable to genetic investigation. Human personality studies have a long history, with various systems trying to make sense of the typical forms and range of variation.

A recent paper did a massive screen of uniformly inbred flies for personality variations. Computerization and automation have revolutionized the animal screening field, as it has so many others, so now flies can be indivually put through a battery of tests with minimal effort to humans, looking for their individual responses to light, to maze choices, spontaneous activity, circadian preferences, sensitivity to odors, etc. These tests were compiled for hundreds of genetically identical flies from birth to death, followed by sequencing of their mRNA expression to see which genes were active. Another batch of more diverse wild-type flies were tested as well to compare what variable genetic influences might be afoot.

Firstly, the differences they observed in these flies were stable over time. They represent true "types" of behavior, despite the lack of genetic input. Secondly, they are limited in landscape. Those flies more active in one test tend to be more active in other tests as well. So the variations in behavior seem to flow from deep-seated categorical types that follow typical patterns within fly development. Which tests should yield correlated scores, and which other ones are more orthogonal, is a little hard to figure out and a matter of subjective taste, so these conclusions about wide-spread correlations in disparate behaviors reflecting personality types is based largely on these researchers knowing their flies on a pretty intimate basis.

A matrix of videos of flies just strolling along, captured by these researchers. Not all flies walk the same way.

For example, they emphasize correlations where they would not have expected them- between, say light sensitivity and overall activity- and non-correlations where they would have expected correlation- say between activity measures of maze walking and free activity. The main observation is that there were a lot of variations among these identical-twin flies. So, just as identical humans can have different personalities, sensitivities, and outlooks, so can flies. 

Is there anything one can say about this genetically? The behavioral variations were themselves not genetically based, but rather due to alternate paths taken down developmental pathways, via either sporadic or experience-based differences. The flies were raised in the same homes, so to speak, but as we know from humans, however similar things may seem on the outside, the individual subjective experience can be very different. At any rate, the developmental pathways leading to the variations are themselves genetically determined, so this exercise was really about learning about how they work, and what range of variation they support/allow.

This analysis of course boils down to how informative the behavioral traits are that the researchers are testing. And obviously, they were not very informative- how does one connect a propensity to turn left when going down a maze with some developmental process? These researchers threw a bunch of statistics at their data, including from the gene expression analysis performed in the sacrificed flies after their mortal trials were over. For instance, among known molecular pathways, metabolic pathway gene expression correlated with activity assays of behavior- not a big surprise. Expression of photo-transduction related genes also correlated with response to light. The biggest correlation was between oxidative phosphorylation gene expression (i.e. mitochondrial activity) with their various activity measurements, which were, after all, the essence of all their assays. In humans, some people are just high-energy, which informs everything they do.

"We found that in all cases, behavioral variation has high dimensionality, that is, many independent axes of variation."

In the end, they conclude that, yes, flies of identical genetic background grow up to have distinct behavioral profiles, or one can say, personalities. Many of these behavioral profiles or traits are independent of each other, indicating several, or even numerous, axes of development where such differences can arise. The researchers estimate 27 dimensions of trait variability, in fact, just from this smattering of tests. But others vary together, forming a sort of personality type, though the choice of assays was obviously very influential in these cross-correlations. These results give a very rough start to the project of figuring out where animal development is less than fully determined, and can thus give rise to the non-genetic variation that provides rich fodder for environmental and social adaptation / specialization. While genes are not directly responsible for this variation, they are responsible for the available range, and thus set the parameters of possible adaptation.

It is sadly typical that these researchers disposed of about 1/3 of their flies at the outset of the study for being insufficiently active. While they are surely correct that these flies would continue to be less active through the rest of the assays, thus giving less data to their automated tests, they did not ask themselves why some flies might choose to think before they leap - so to speak. Were they genetically defective? The flies were identical to a matter of a handful of single nucleotide variations. If inbreeding was a problem, all the flies would have been equally affected. So it is likely that one of the most significant personality traits was summarily excluded out of raw institutionalized bias against the more introverted fly, conveniently veiled by claims of technical limitations. Hey hey, ho ho!

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