TY - JOUR
T1 - Mutation and human exceptionalism
T2 - Our future genetic load
AU - Lynch, Michael
N1 - Publisher Copyright:
© 2016 by the Genetics Society of America.
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84979941565&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979941565&partnerID=8YFLogxK
U2 - 10.1534/genetics.115.180471
DO - 10.1534/genetics.115.180471
M3 - Article
C2 - 26953265
AN - SCOPUS:84979941565
SN - 0016-6731
VL - 202
SP - 869
EP - 875
JO - Genetics
JF - Genetics
IS - 3
ER -