Perspective: Spontaneous deleterious mutation

Michael Lynch, Jeff Blanchard, David Houle, Travis Kibota, Stewart Schultz, Larissa Vassilieva, John Willis

Research output: Contribution to journalArticle

358 Citations (Scopus)

Abstract

Mildly deleterious mutation has been invoked as a leading explanation for a diverse array of observations in evolutionary genetics and molecular evolution and is thought to be a significant risk of extinction for small populations. However, much of the empirical evidence for the deleterious-mutation process derives from studies of Drosophila melanogaster, some of which have been called into question. We review a broad array of data that collectively support the hypothesis that deleterious mutations arise in flies at rate of about one per individual per generation, with the average mutation decreasing fitness by about only 2% in the heterozygous state. Empirical evidence from microbes, plants, and several other animal species provide further support for the idea that most mutations have only mildly deleterious effects on fitness, and several other species appear to have genomic mutation rates that are of the order of magnitude observed in Drosophila. However, there is mounting evidence that some organisms have genomic deleterious mutation rates that are substantially lower than one per individual per generation. These lower rates may be at least partially reconciled with the Drosophila data by taking into consideration the number of germline cell divisions per generation. To fully resolve the existing controversy over the properties of spontaneous mutations, a number of issues need to be clarified. These include the form of the distribution of mutational effects and the extent to which this is modified by the environmental and genetic background and the contribution of basic biological features such as generation length and genome size to interspecific differences in the genomic mutation rate. Once such information is available, it should be possible to make a refined statement about the long-term impact of mutation on the genetic integrity of human populations subject to relaxed selection resulting from modern medical procedures.

Original languageEnglish (US)
Pages (from-to)645-663
Number of pages19
JournalEvolution
Volume53
Issue number3
StatePublished - Jun 1 1999
Externally publishedYes

Fingerprint

mutation
Mutation
Mutation Rate
Molecular Evolution
Drosophila
genomics
Genome Size
fitness
Medical Genetics
Drosophila melanogaster
Diptera
Cell Division
Population
human population
genetic background
cell division
germ cells
extinction
genome
rate

Keywords

  • Deleterious mutation
  • Fitness
  • Mutation
  • Mutation rate
  • Mutational effect

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Agricultural and Biological Sciences(all)

Cite this

Lynch, M., Blanchard, J., Houle, D., Kibota, T., Schultz, S., Vassilieva, L., & Willis, J. (1999). Perspective: Spontaneous deleterious mutation. Evolution, 53(3), 645-663.

Perspective : Spontaneous deleterious mutation. / Lynch, Michael; Blanchard, Jeff; Houle, David; Kibota, Travis; Schultz, Stewart; Vassilieva, Larissa; Willis, John.

In: Evolution, Vol. 53, No. 3, 01.06.1999, p. 645-663.

Research output: Contribution to journalArticle

Lynch, M, Blanchard, J, Houle, D, Kibota, T, Schultz, S, Vassilieva, L & Willis, J 1999, 'Perspective: Spontaneous deleterious mutation', Evolution, vol. 53, no. 3, pp. 645-663.
Lynch M, Blanchard J, Houle D, Kibota T, Schultz S, Vassilieva L et al. Perspective: Spontaneous deleterious mutation. Evolution. 1999 Jun 1;53(3):645-663.
Lynch, Michael ; Blanchard, Jeff ; Houle, David ; Kibota, Travis ; Schultz, Stewart ; Vassilieva, Larissa ; Willis, John. / Perspective : Spontaneous deleterious mutation. In: Evolution. 1999 ; Vol. 53, No. 3. pp. 645-663.
@article{76ca6ca0f35748a48697daa31803fdbc,
title = "Perspective: Spontaneous deleterious mutation",
abstract = "Mildly deleterious mutation has been invoked as a leading explanation for a diverse array of observations in evolutionary genetics and molecular evolution and is thought to be a significant risk of extinction for small populations. However, much of the empirical evidence for the deleterious-mutation process derives from studies of Drosophila melanogaster, some of which have been called into question. We review a broad array of data that collectively support the hypothesis that deleterious mutations arise in flies at rate of about one per individual per generation, with the average mutation decreasing fitness by about only 2{\%} in the heterozygous state. Empirical evidence from microbes, plants, and several other animal species provide further support for the idea that most mutations have only mildly deleterious effects on fitness, and several other species appear to have genomic mutation rates that are of the order of magnitude observed in Drosophila. However, there is mounting evidence that some organisms have genomic deleterious mutation rates that are substantially lower than one per individual per generation. These lower rates may be at least partially reconciled with the Drosophila data by taking into consideration the number of germline cell divisions per generation. To fully resolve the existing controversy over the properties of spontaneous mutations, a number of issues need to be clarified. These include the form of the distribution of mutational effects and the extent to which this is modified by the environmental and genetic background and the contribution of basic biological features such as generation length and genome size to interspecific differences in the genomic mutation rate. Once such information is available, it should be possible to make a refined statement about the long-term impact of mutation on the genetic integrity of human populations subject to relaxed selection resulting from modern medical procedures.",
keywords = "Deleterious mutation, Fitness, Mutation, Mutation rate, Mutational effect",
author = "Michael Lynch and Jeff Blanchard and David Houle and Travis Kibota and Stewart Schultz and Larissa Vassilieva and John Willis",
year = "1999",
month = "6",
day = "1",
language = "English (US)",
volume = "53",
pages = "645--663",
journal = "Evolution; international journal of organic evolution",
issn = "0014-3820",
publisher = "Society for the Study of Evolution",
number = "3",

}

TY - JOUR

T1 - Perspective

T2 - Spontaneous deleterious mutation

AU - Lynch, Michael

AU - Blanchard, Jeff

AU - Houle, David

AU - Kibota, Travis

AU - Schultz, Stewart

AU - Vassilieva, Larissa

AU - Willis, John

PY - 1999/6/1

Y1 - 1999/6/1

N2 - Mildly deleterious mutation has been invoked as a leading explanation for a diverse array of observations in evolutionary genetics and molecular evolution and is thought to be a significant risk of extinction for small populations. However, much of the empirical evidence for the deleterious-mutation process derives from studies of Drosophila melanogaster, some of which have been called into question. We review a broad array of data that collectively support the hypothesis that deleterious mutations arise in flies at rate of about one per individual per generation, with the average mutation decreasing fitness by about only 2% in the heterozygous state. Empirical evidence from microbes, plants, and several other animal species provide further support for the idea that most mutations have only mildly deleterious effects on fitness, and several other species appear to have genomic mutation rates that are of the order of magnitude observed in Drosophila. However, there is mounting evidence that some organisms have genomic deleterious mutation rates that are substantially lower than one per individual per generation. These lower rates may be at least partially reconciled with the Drosophila data by taking into consideration the number of germline cell divisions per generation. To fully resolve the existing controversy over the properties of spontaneous mutations, a number of issues need to be clarified. These include the form of the distribution of mutational effects and the extent to which this is modified by the environmental and genetic background and the contribution of basic biological features such as generation length and genome size to interspecific differences in the genomic mutation rate. Once such information is available, it should be possible to make a refined statement about the long-term impact of mutation on the genetic integrity of human populations subject to relaxed selection resulting from modern medical procedures.

AB - Mildly deleterious mutation has been invoked as a leading explanation for a diverse array of observations in evolutionary genetics and molecular evolution and is thought to be a significant risk of extinction for small populations. However, much of the empirical evidence for the deleterious-mutation process derives from studies of Drosophila melanogaster, some of which have been called into question. We review a broad array of data that collectively support the hypothesis that deleterious mutations arise in flies at rate of about one per individual per generation, with the average mutation decreasing fitness by about only 2% in the heterozygous state. Empirical evidence from microbes, plants, and several other animal species provide further support for the idea that most mutations have only mildly deleterious effects on fitness, and several other species appear to have genomic mutation rates that are of the order of magnitude observed in Drosophila. However, there is mounting evidence that some organisms have genomic deleterious mutation rates that are substantially lower than one per individual per generation. These lower rates may be at least partially reconciled with the Drosophila data by taking into consideration the number of germline cell divisions per generation. To fully resolve the existing controversy over the properties of spontaneous mutations, a number of issues need to be clarified. These include the form of the distribution of mutational effects and the extent to which this is modified by the environmental and genetic background and the contribution of basic biological features such as generation length and genome size to interspecific differences in the genomic mutation rate. Once such information is available, it should be possible to make a refined statement about the long-term impact of mutation on the genetic integrity of human populations subject to relaxed selection resulting from modern medical procedures.

KW - Deleterious mutation

KW - Fitness

KW - Mutation

KW - Mutation rate

KW - Mutational effect

UR - http://www.scopus.com/inward/record.url?scp=0032815107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032815107&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0032815107

VL - 53

SP - 645

EP - 663

JO - Evolution; international journal of organic evolution

JF - Evolution; international journal of organic evolution

SN - 0014-3820

IS - 3

ER -