In evolution, there is a tradeoff between genomes that are maximally fit but particularly vulnerable to deleterious mutations, and those that are more capable of ignoring deleterious mutations that are less maximally fit, a type of genome known as a "flat" genome. Hence, the notion "survival of the flattest".
But, it turns out that the trade off is not a perfect one, so minimizing the load in a genome of deleterious mutations still confers improved fitness, according to a recent pre-print:
Populations exposed to a high mutation rate harbor abundant deleterious genetic variation, leading to depressed mean fitness. This reduction in mean fitness presents an opportunity for selection to restore adaptation through the evolution of mutational robustness. In extreme cases, selection for mutational robustness can lead to "flat" genotypes (with low fitness but high robustness) out-competing "fit" genotypes with high fitness but low robustness-a phenomenon known as "survival of the flattest".
While this effect was previously explored using the digital evolution system Avida, a complete analysis of the local fitness landscapes of "fit" and "flat" genotypes has been lacking, leading to uncertainty about the genetic basis of the survival of the flattest effect.
Here, we repeated the survival of the flattest study and analyzed the mutational neighborhoods of fit and flat genotypes. We found that flat genotypes, compared to the fit genotypes, had a reduced likelihood of deleterious mutations as well as an increased likelihood of neutral and, surprisingly, of lethal mutations. This trend holds for mutants one to four substitutions away from the wild-type sequence. We also found that flat genotypes have, on average, no epistasis between mutations, while fit genotypes have, on average, positive epistasis.
Our results demonstrate that the genetic causes of mutational robustness on complex fitness landscapes are multifaceted. While the traditional idea of the survival of the flattest effect emphasized the evolution of increased neutrality, others have argued for increased mutational sensitivity in response to strong mutational loads. Our results show that both increased neutrality and increased lethality can lead to the evolution of mutational robustness. Furthermore, strong negative epistasis is not required for mutational sensitivity to lead to mutational robustness. Overall, these results suggest that mutational robustness is achieved by minimizing heritable deleterious variation.
How does this apply to humans?
Lot of genetic cognitive and mental health issues in humans (e.g. psychosis) have a stronger association to overall mutation load than to any particular gene. If selection optimizes mutational load reduction, then this suggests that cognitive and mental health issues may have been very weak fitness reducing traits for most of human history. The average load is high enough that 1% of the population has psychosis.
But, before this conclusion, the frequency with which such loads are present might have been interpreted as an equilibrium result with the load favored because it enhanced robustness to future mutations despite the fitness reduction associated with it, even if the fitness costs of these conditions was rather high.
thanks, i had in mind something more concrete
does a person who goes to harvard and excels in sports and enjoys all the gifts have probably a low mutational load
and someone with severe mental and health problems (probably) have a high mutational load.
does the homeless person and the sickly probably have high mutational load and someone who is a super model and goes to a top uni have a low mutational load.
why some people enjoy the good things in life and then there are the homeless and sick is something i've long wondered.
Socio-economic success has to do with a lot more than genetics. Most of Europe's high aristocracy has a high mutational load due to prolonged inbreeding.
lets take psychosis, or other health problems, if someone has psychosis what conclusions can be drawn about their mutational load
Psychosis has a strong association with overall mutational load, with most of the genetic indicators of schizophrenia and bipolar disorder overlapping and only a minor portion specific to one particular manifestation or the other. Thus, the "syndrome" (i.e. phenotype defined by symptoms) that makes up psychosis is not caused by particular genes so much as more deleterious mutations in the right general area of the genome than a very complex assembly of genes that govern cognitive processes than the genome is robust enough to bear.
And something like 80%-90% of people who have genes and heredity putting them at very high risk of psychosis don't ever end up manifesting that phenotype, so usually, this area of the genome is quite robust although sometimes if just the wrong pieces coincide a high but usually not symptomatic level of deleterious mutations give rise to the psychosis phenotype.
So, the typical person with psychosis as a high but not lethally high load of deleterious mutations in part of a large complex of genes relative to cognitive processes who was unlikely enough be the person who rolled the dice and ended up with those deleterious mutations in just the right places to give rise to the psychosis syndrome, which is a generalized response that is a bit like the fever of high deleterious mutation load in genes related to cognitive function.
What is surprising is that you can have 1% of the population, generation after generation for centuries have this syndrome, rather than having natural selection thin it out significantly over time (although mutations that can lead to psychosis are probably significant less common in Africans, or at least, in African-Americans where the incidence of psychosis is far below the global average). This strongly suggests that the selective fitness pressure on this syndrome that would tend to cause people to have lower mutation loads in this area was very, very weak for most populations.
(Autism has a somewhat similar etiology with high mutation loads of lots of varied configurations leading a cognitive module to screw up in a particular way that it is naturally prone to if any part of that fined tuned set of genes is seriously amiss. But, autism involve more de novo mutations with large effect, rather than the many smaller effect mutations seen in psychosis that are mostly inherited, because autism has a much more negative effective on one's ability to survive and reproduce.)
interesting. though some forms of autism probably dont have a negative effect. like asperger's
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