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Title: Deleterious background selection with recombination

Abstract

An analytic expression for the expected nucleotide diversity is obtained for a neutral locus in a region with deleterious mutation and recombination. Our analytic results are used to predict levels of variation for the entire third chromosome of Drosophila melanogaster. The predictions are consistent with the low levels of variation that have been observed at loci near the centromeres of the third chromosome of D. melanogaster. However, the low levels of variation observed near the tips of this chromosome are not predicted using currently available estimates of the deleterious mutation rate and of selection coefficients. If considerably smaller selection coefficients are assumed, the low observed levels of variation at the tips of the third chromosome are consistent with the background selection model. 33 refs., 4 figs., 1 tab.

Authors:
 [1];  [2]
  1. Univ. of California, Irvine, CA (United States)
  2. National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)
Publication Date:
OSTI Identifier:
535353
Resource Type:
Journal Article
Resource Relation:
Journal Name: Genetics; Journal Volume: 141; Journal Issue: 4; Other Information: PBD: Dec 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; 99 MATHEMATICS, COMPUTERS, INFORMATION SCIENCE, MANAGEMENT, LAW, MISCELLANEOUS; DROSOPHILA; GENETICS; GENES; GENE RECOMBINATION; GENETIC VARIABILITY; GENE MUTATIONS; GENETIC MAPPING; MUTATION FREQUENCY; NUCLEOTIDES; ANALYTIC FUNCTIONS; CHROMOSOMES; CHROMOSOMAL ABERRATIONS; CENTROMERES

Citation Formats

Hudson, R.R., and Kaplan, N.L. Deleterious background selection with recombination. United States: N. p., 1995. Web.
Hudson, R.R., & Kaplan, N.L. Deleterious background selection with recombination. United States.
Hudson, R.R., and Kaplan, N.L. 1995. "Deleterious background selection with recombination". United States. doi:.
@article{osti_535353,
title = {Deleterious background selection with recombination},
author = {Hudson, R.R. and Kaplan, N.L.},
abstractNote = {An analytic expression for the expected nucleotide diversity is obtained for a neutral locus in a region with deleterious mutation and recombination. Our analytic results are used to predict levels of variation for the entire third chromosome of Drosophila melanogaster. The predictions are consistent with the low levels of variation that have been observed at loci near the centromeres of the third chromosome of D. melanogaster. However, the low levels of variation observed near the tips of this chromosome are not predicted using currently available estimates of the deleterious mutation rate and of selection coefficients. If considerably smaller selection coefficients are assumed, the low observed levels of variation at the tips of the third chromosome are consistent with the background selection model. 33 refs., 4 figs., 1 tab.},
doi = {},
journal = {Genetics},
number = 4,
volume = 141,
place = {United States},
year = 1995,
month =
}
  • Free-living bacteria are usually thought to have large effective population sizes, and so tiny selective differences can drive their evolution. However, because recombination is infrequent, “background selection” against slightly deleterious alleles should reduce the effective population size (N e) by orders of magnitude. For example, for a well-mixed population with 10 12 individuals and a typical level of homologous recombination (r/m= 3, i.e., nucleotide changes due to recombination [r] occur at 3 times the mutation rate [m]), we predict that N e is<10 7. An argument for high N e values for bacteria has been the high genetic diversity withinmore » many bacterial “species,” but this diversity may be due to population structure: diversity across subpopulations can be far higher than diversity within a subpopulation, which makes it difficult to estimate N e correctly. Given an estimate ofN e, standard population genetics models imply that selection should be sufficient to drive evolution if N e ×s is >1, where s is the selection coefficient. We found that this remains approximately correct if background selection is occurring or when population structure is present. Overall, we predict that even for free-living bacteria with enormous populations, natural selection is only a significant force ifs is above 10 -7 or so. Because bacteria form huge populations with trillions of individuals, the simplest theoretical prediction is that the better allele at a site would predominate even if its advantage was just 10 -9 per generation. In other words, virtually every nucleotide would be at the local optimum in most individuals. A more sophisticated theory considers that bacterial genomes have millions of sites each and selection events on these many sites could interfere with each other, so that only larger effects would be important. However, bacteria can exchange genetic material, and in principle, this exchange could eliminate the interference between the evolution of the sites. In conclusion, we used simulations to confirm that during multisite evolution with realistic levels of recombination, only larger effects are important. We propose that advantages of less than 10 -7are effectively neutral.« less
  • ABSTRACT Free-living bacteria are usually thought to have large effective population sizes, and so tiny selective differences can drive their evolution. However, because recombination is infrequent, “background selection” against slightly deleterious alleles should reduce the effective population size (N e) by orders of magnitude. For example, for a well-mixed population with 10 12individuals and a typical level of homologous recombination (r/m= 3, i.e., nucleotide changes due to recombination [r] occur at 3 times the mutation rate [m]), we predict thatN eis<10 7. An argument for highN evalues for bacteria has been the high genetic diversity within many bacterial “species,” butmore » this diversity may be due to population structure: diversity across subpopulations can be far higher than diversity within a subpopulation, which makes it difficult to estimateN ecorrectly. Given an estimate ofN e, standard population genetics models imply that selection should be sufficient to drive evolution ifN e×sis >1, wheresis the selection coefficient. We found that this remains approximately correct if background selection is occurring or when population structure is present. Overall, we predict that even for free-living bacteria with enormous populations, natural selection is only a significant force ifsis above 10 -7or so. IMPORTANCEBecause bacteria form huge populations with trillions of individuals, the simplest theoretical prediction is that the better allele at a site would predominate even if its advantage was just 10 -9per generation. In other words, virtually every nucleotide would be at the local optimum in most individuals. A more sophisticated theory considers that bacterial genomes have millions of sites each and selection events on these many sites could interfere with each other, so that only larger effects would be important. However, bacteria can exchange genetic material, and in principle, this exchange could eliminate the interference between the evolution of the sites. We used simulations to confirm that during multisite evolution with realistic levels of recombination, only larger effects are important. We propose that advantages of less than 10 -7are effectively neutral.« less
  • Based on the Fisher-Muller theory of the evolution of recombination, an argument can be constructed predicting that a recessive allele favoring recombination will be favored, if there are either favorable or deleterious mutants occurring at other loci. In this case there is no clear distinction between individual and group selection. Computer simulation of populations segregating for recessive or dominant recombination alleles showed selection favoring recombination, except in the case of a dominant recombination allele with deleterious background mutants. The relationship of this work to parallel investigations by Williams and by Strobeck, Maynard Smith, and Charlesworth is explored. All seem tomore » rely on the same phenomenon. There seems no reason to assume that the evolution of recombination must have occurred by group selection.« less
  • Recombination walking is based on the genetic selection of specific human clones from a yeast artificial chromosome (YAC) library by homologous recombination. The desired clone is selected from a pooled (unorderd) YAC library, eliminating labor-intensive steps typically used in organizing and maintaining ordered YAC libraries. Recombination walking represents an efficient approach to library screening and is well suited for chromosome-walking approaches to the isolation of genes associated with common diseases. 29 refs., 4 figs., 1 tab.
  • The procedure for the selection of a temperature-sensitive recombination mutant in Drosophila is described. Use of this procedure has led to the recovery of three alleles at a new recombination locus called rec-1, located within the region of chromosome 3 circumscribed by Deficiency(3R)sbd/sup 105/. One allele, rec-1/sup 26/, is temperature sensitive, and the other two alleles, rec-1/sup 6/ and rec-1/sup 16/, are temperature insensitive. Gene dosage studies reveal rec-1/sup 26/ to be a leaky mutant with greater recombination activity in two doses than in one. The other two alleles show no dose response, implying that they may be null mutants.more » The temperature response curves of rec-1/sup 26/ as a homozygote and in heteroallelic combination with rec-1/sup 16/ suggest that the sharp decrease in recombination between 28/sup 0/ and 31/sup 0/ indicates temperature denaturation of an enzyme or other protein specified by the mutant and associated with the recombination process. The ability of small changes in temperature to reverse or abolish polarity in recombination along the X chromosome arm in rec-1/sup 26//rec-1/sup 16/ females brings into question the use of the ''polarity'' criterion to partition mutants into two functional types, i.e., precondition mutants that display polarity and exchange mutants that do not. Evidence that rec-1 may be part of a complex locus residing in a chromosome segment harboring a variety of recombination-related genes is presented.« less