Grab the Gauge
08-17-2016, 05:08 AM
http://www.genetics.org/content/202/3/869
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.
Over the course of the experiment, the mean number of offspring per mating declined at an average rate of 3.35% per generation, although most of the change occurred within the first 6 generations, rendering line maintenance difficult and likely imposing some selection against further decline. Body weight in these lines declined by 0.5% per generation, and obvious phenotypic abnormalities accumulated at rates of 0.68% per generation
The preceding arguments need not imply that human behavior by natural selection has come to a standstill (Reed and Aquadro 2006), one key issue being that natural selection is a function of both survival and reproduction. Even if variance in survival were to be eliminated entirely, phenotypes that are associated with reproductive output will inevitably be promoted by the blind forces of selection. However, another aspect of modern human behavior—the tendency toward families of similar size (the two-child syndrome in middle-class neighborhoods in westernized societies)—may thwart this aspect of selection as well. Notably, this very strategy (equilibration of family sizes) has been used to accumulate deleterious mutations in experimental populations of Drosophila, yielding a 0.2–2% decline in fitness per generation (Shabalina et al. 1997).
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.
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.
Despite 3 billion years of natural selection, in no known organism has the base-substitution mutation rate evolved to Embedded Image per nucleotide site per cell division (Sung et al. 2012). Because this lower limit is not far from what occurs in the human germline per cell division [Embedded Image per nucleotide site per cell division (Drake et al. 1998; Lynch 2008)], no amount of human intervention at the molecular level is likely to improve the situation (although diminishing progeny production via sperm from old males would help).
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.
Over the course of the experiment, the mean number of offspring per mating declined at an average rate of 3.35% per generation, although most of the change occurred within the first 6 generations, rendering line maintenance difficult and likely imposing some selection against further decline. Body weight in these lines declined by 0.5% per generation, and obvious phenotypic abnormalities accumulated at rates of 0.68% per generation
The preceding arguments need not imply that human behavior by natural selection has come to a standstill (Reed and Aquadro 2006), one key issue being that natural selection is a function of both survival and reproduction. Even if variance in survival were to be eliminated entirely, phenotypes that are associated with reproductive output will inevitably be promoted by the blind forces of selection. However, another aspect of modern human behavior—the tendency toward families of similar size (the two-child syndrome in middle-class neighborhoods in westernized societies)—may thwart this aspect of selection as well. Notably, this very strategy (equilibration of family sizes) has been used to accumulate deleterious mutations in experimental populations of Drosophila, yielding a 0.2–2% decline in fitness per generation (Shabalina et al. 1997).
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.
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.
Despite 3 billion years of natural selection, in no known organism has the base-substitution mutation rate evolved to Embedded Image per nucleotide site per cell division (Sung et al. 2012). Because this lower limit is not far from what occurs in the human germline per cell division [Embedded Image per nucleotide site per cell division (Drake et al. 1998; Lynch 2008)], no amount of human intervention at the molecular level is likely to improve the situation (although diminishing progeny production via sperm from old males would help).