Mutation and Human Exceptionalism: Our Future Genetic Load

Abstract

Although the human germline mutation rate is higher than that in any other well-studied species, the rate is not exceptional once the effective genome size and effective population size are taken into consideration. Human somatic mutation rates are substantially elevated above those in the germline, but this is also seen in other species.
What is exceptional about humans is the recent detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition, potentially measurable on the timescale of a few generations in westernized societies, and because the brain is a particularly large mutational target, this is of particular concern. Ultimately, the price will have to be covered by further investment in various forms of medical intervention.
Resolving the uncertainties of the magnitude and timescale of these effects will require the establishment of stable, standardized, multigenerational measurement procedures for various human traits.
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The Long-Term Prognosis
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Thus, without any compelling counterarguments at this time, it remains difficult to escape the conclusion that numerous physical and psychological attributes are likely to slowly deteriorate in technologically advanced societies, with notable changes in average preintervention phenotypes expected on a timescale of a few generations, i.e., 100 years, in societies where medical care is widely applied. In the United States, the incidences of a variety of afflictions including autism, male infertility, asthma, immune-system disorders, diabetes, etc., already exhibit increases exceeding the expected rate. Much of this change is almost certainly due to alterations in environmental factors. However, mitigating these effects by modifications in behavior and/or medical intervention will also simply exacerbate the issues noted above by relaxing selection on any underlying genetic factors.
Determining the genetic contribution to any long-term trend in phenotypic attributes will require the development and implementation of standardized measurement methods that control for historical changes in ascertainment and environmental effects. Given the massive support devoted to biomedical research, surely this is a goal worth pursuing.

One final matter worthy of consideration is the fact that most prior work on the effects of mutations has focused on simple measures of survival and reproduction, usually in model invertebrate systems. Little consideration has been given to behavior, but work with Caenorhabditis elegans, a nematode with a relatively simple nervous system, suggests a rate of decline in behavioral performance similar to that for immediate fitness traits (Ajie et al. 2005). This observational work may substantially underestimate the mutational vulnerability of the world’s most complex organ, the human brain. Because human brain function is governed by the expression of thousands of genes, the germline mutation rate to psychological disorders may be unusually high.
At least 30% of individuals with autism spectrum disorders appear to acquire such behaviors by de novo mutation (Iossifov et al. 2015). Notably, human brain cells also incur up to dozens of mobile-element insertions per cell (Erwin et al. 2014; Richardson et al. 2014), implying a level of somatic mutation far beyond the expectation noted above based on point mutations.


Arguably, by providing a mechanism for partitioning of mentally demanding tasks, societal living may serve as still another way by which selection is relaxed on traits within individuals, although it may also be argued that complex societies impose selection for novel ways of processing information. It has been suggested that there has been a slow decline in intelligence in the United States and the United Kingdom over the past century (Crabtree 2013; Woodley 2015), although again the underlying issues with respect to environmental factors have not been fully resolved, and not surprisingly these arguments are controversial. The key point here is that the one truly exceptional human attribute, brain function, may be particularly responsive to mutation accumulation, possibly exhibiting a response to relaxed selection greater than the 1% benchmark suggested above.

A fitness decline of a few percent on the timescale of a century is on the order of the rate of global warming, and that is part of the problem. What will it take to promote serious discourse on the slowly emerging, long-term negative consequences of policies jointly promoted by political, social, and religious factors?
Should such a discussion even be pursued or should the process of accelerated genetic change simply be allowed to run its course—a slow walk down the path to what Hamilton (2001) called “the great Planetary Hospital”? Unlike global environmental change, there is no obvious technological fix for the uniquely human goal of intentionally ameliorating the effects of mutation, nor is there a simple ethical imperative for doing otherwise, short of refocusing our ethical goals on future descendants.
Unless some altered course is taken, as improved biomedical procedures continue to minimize the cumulative consequences of our genetic (and/or environmentally induced) afflictions, and the associated biomedical industries reap the financial rewards, this will come at a progressively increasing cost for individuals with the resources and/or desires to apply such solutions.
Source (Genetics)

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