1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Animal Biosciences
  4. Volume 11, 2023
  5. Article

Annual Review of Animal Biosciences

Volume 11, 2023

Interrogating the Roles of Mutation–Selection Balance, Heterozygote Advantage, and Linked Selection in Maintaining Recessive Lethal Variation in Natural Populations

Abstract

For nearly a century, evolutionary biologists have observed chromosomes that cause lethality when made homozygous persisting at surprisingly high frequencies (>25%) in natural populations of many species. The evolutionary forces responsible for the maintenance of such detrimental mutations have been heavily debated—are some lethal mutations under balancing selection? We suggest that mutation–selection balance alone cannot explain lethal variation in nature and the possibility that other forces play a role. We review the potential that linked selection in particular may drive maintenance of lethal alleles through associative overdominance or linkage to beneficial mutations or by reducing effective population size. Over the past five decades, investigation into this mystery has tapered. During this time, key scientific advances have provided the ability to collect more accurate data and analyze them in new ways, making the underlying genetic bases and evolutionary forces of lethal alleles timely for study once more.

Keyword(s): associative overdominance, heterozygote advantage, lethal, linked selection, mutation–selection balance, supergene
Loading

Article metrics loading...

/content/journals/10.1146/annurev-animal-050422-092520
2023-02-15
2024-05-09
Loading full text...

Full text loading...

/deliver/fulltext/animal/11/1/annurev-animal-050422-092520.html?itemId=/content/journals/10.1146/annurev-animal-050422-092520&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Kimura M. 1968. Evolutionary rate at the molecular level. Nature 217:624–26
     [Google Scholar]
  2. 2.
    Simmons MJ, Crow JF. 1977. Mutations affecting fitness in Drosophila populations. Annu. Rev. Genet. 11:49–78
     [Google Scholar]
  3. 3.
    Charlesworth D, Charlesworth B. 1987. Inbreeding depression and its evolutionary consequences. Annu. Rev. Ecol. Syst. 18:237–68
     [Google Scholar]
  4. 4.
    Ballinger MA, Noor MAF. 2018. Are lethal alleles too abundant in humans?. Trends Genet. 34:287–89
     [Google Scholar]
  5. 5.
    McCune AR, Fuller RC, Aquilina AA, Dawley RM, Fadool JM et al. 2002. A low genomic number of recessive lethals in natural populations of bluefin killifish and zebrafish. Science 296:2398–401
     [Google Scholar]
  6. 6.
    Derks MFL, Gjuvsland AB, Bosse M, Lopes MS, van Son M et al. 2019. Loss of function mutations in essential genes cause embryonic lethality in pigs. PLOS Genet. 15:331008055
     [Google Scholar]
  7. 7.
    Lewontin RC. 1974. The Genetic Basis of Evolutionary Change New York: Columbia Univ. Press
  8. 8.
    Derks MFL, Lopes MS, Bosse M, Madsen O, Dibbits B et al. 2018. Balancing selection on a recessive lethal deletion with pleiotropic effects on two neighboring genes in the porcine genome. PLOS Genet. 14:9e1007661
     [Google Scholar]
  9. 9.
    Spiess EB, Helling RB, Capenos MR. 1963. Linkage of autosomal lethals from a laboratory population of Drosophila melanogaster. Genetics 48:101377–88
     [Google Scholar]
  10. 10.
    Haldane JBS. 1937. The effect of variation on fitness. Am. Nat. 71:735337–49
     [Google Scholar]
  11. 11.
    Haag-Liautard C, Dorris M, Maside X, Macaskill S, Halligan DL et al. 2007. Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila. Nature 445:712382–85
     [Google Scholar]
  12. 12.
    Keightley PD, Trivedi U, Thomson M, Oliver F, Kumar S, Blaxter ML. 2009. Analysis of the genome sequences of three Drosophila melanogaster spontaneous mutation accumulation lines. Genome Res. 19:71195–201
     [Google Scholar]
  13. 13.
    Schrider DR, Houle D, Lynch M, Hahn MW. 2013. Rates and genomic consequences of spontaneous mutational events in Drosophila melanogaster. Genetics 194:4937–54
     [Google Scholar]
  14. 14.
    Huang W, Lyman RF, Lyman RA, Carbone MA, Harbison ST et al. 2016. Spontaneous mutations and the origin and maintenance of quantitative genetic variation. eLife 5:e14625
     [Google Scholar]
  15. 15.
    Barroso GV, Dutheil JY. 2021. Mutation rate variation shapes genome-wide diversity in Drosophila melanogaster. bioRxiv 460667. https://doi.org/10.1101/2021.09.16.460667
    [Crossref]
  16. 16.
    Mukai T, Chigusa SI, Mettler LE, Crow JF. 1972. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics 72:2335–55
     [Google Scholar]
  17. 17.
    Dobzhansky T, Spassky B, Tidwell T. 1963. Genetics of natural populations. 32. Inbreeding and the mutational and balanced genetic loads in natural populations of Drosophila pseudoobscura. Genetics 48:361–73
     [Google Scholar]
  18. 18.
    Malogolowkin-Cohen C, Levene H, Dobzhanksy NP, Simmons AS. 1964. Inbreeding and the mutational and balanced loads in natural populations. Genetics 50:1299–311
     [Google Scholar]
  19. 19.
    Mestres F, Pegueroles G, Prevosti A, Serra L. 1990. Colonization of America by Drosophila subobscura: lethal genes and the problem of the O5 inversion. Evolution 44:71823–36
     [Google Scholar]
  20. 20.
    Watanabe TK, Oshima C. 1970. Persistence of lethal genes in Japanese natural populations of Drosophila melanogaster. Genetics 64:193–106
     [Google Scholar]
  21. 21.
    Apirion D, Zohary D. 1961. Chlorophyll lethal in natural populations of the orchard grass (Dactylis glomerata L.): a case of balanced polymorphism in plants. Genetics 46:393–99
     [Google Scholar]
  22. 22.
    Dobzhansky T. 1970. Genetics of the Evolutionary Process New York: Columbia Univ. Press
  23. 23.
    Hiraizumi Y, Crow JF. 1960. Heterozygous effects on viability, fertility, rate of development, and longevity of Drosophila chromosomes that are lethal when homozygous. Genetics 45:81071–83
     [Google Scholar]
  24. 24.
    Sturtevant AH. 1937. Autosomal lethals in wild populations of Drosophila pseudoöbscura. Biol. Bull. 73:3542–51
     [Google Scholar]
  25. 25.
    Grossen C, Neuenschwander S, Perrin N. 2012. The balanced lethal system of crested newts: A ghost of sex chromosomes past?. Am. Nat. 180:6e174–83
     [Google Scholar]
  26. 26.
    Zhao L, Charlesworth B. 2016. Resolving the conflict between associative overdominance and background selection. Genetics 203:1315–34
     [Google Scholar]
  27. 27.
    Becher H, Jackson BC, Charlesworth B. 2020. Patterns of genetic variability in genomic regions with low rates of recombination. Curr. Biol. 30:194–100.e3
     [Google Scholar]
  28. 28.
    Gilbert KJ, Pouyet F, Excoffier L, Peischl S. 2020. Transition from background selection to associative overdominance promotes diversity in regions of low recombination. Curr. Biol. 30:1101–7.e3
     [Google Scholar]
  29. 29.
    Comeron JM. 2014. Background selection as baseline for nucleotide variation across the Drosophila genome. PLOS Genet. 10:6e1004434
     [Google Scholar]
  30. 30.
    Stephan W. 2010. Genetic hitchhiking versus background selection: the controversy and its implications. Philos. Trans. R. Soc. B 365:15441245–53
     [Google Scholar]
  31. 31.
    Watanabe TK, Oshima C. 1966. Distribution of natural lethal genes on the second chromosome of Drosophila melanogaster. Genet. Mag. 41:5367–78
     [Google Scholar]
  32. 32.
    Ytterborn KH. 1968. The persistency in experimental population of second chromosome recessive lethals obtained after irradiation of spermatogonia and spermatozoa in Drosophila melanogaster. Hereditas 60:1–233–71
     [Google Scholar]
  33. 33.
    Kirkpatrick M. 2010. How and why chromosome inversions evolve. PLOS Biol. 8:9e1000501
     [Google Scholar]
  34. 34.
    Mestres F, Balanyà J, Arenas C, Solé E, Serra L. 2001. Colonization of America by Drosophila subobscura: heterotic effect of chromosomal arrangements revealed by the persistence of lethal genes. PNAS 98:169167–70
     [Google Scholar]
  35. 35.
    Mestres F, Balanyà J, Pascual M, Arenas C, Gilchrist GW et al. 2009. Evolution of Chilean colonizing populations of Drosophila subobscura: lethal genes and chromosomal arrangements. Genetica 136:137–48
     [Google Scholar]
  36. 36.
    Coyne JA, Aulard S, Berry A. 1991. Lack of underdominance in a naturally occurring pericentric inversion in Drosophila melanogaster and its implications for chromosome evolution. Genetics 129:3791–802
     [Google Scholar]
  37. 37.
    Albornoz J, Domínguez A. 1994. Inversion polymorphism and accumulation of lethals in selected lines of Drosophila melanogaster. Heredity 73:192–97
     [Google Scholar]
  38. 38.
    Yang YY, Lin FJ, Chang HY. 2002. Comparison of recessive lethal accumulation in inversion-bearing and inversion-free chromosomes in Drosophila. Zool. Stud. 41:3271–82
     [Google Scholar]
  39. 39.
    Hasson E, Eanes WF. 1996. Contrasting histories of three gene regions associated with In(3L)Payne of Drosophila melanogaster. Genetics 144:41565–75
     [Google Scholar]
  40. 40.
    Navarro A, Betrán E, Barbadilla A, Ruiz A. 1997. Recombination and gene flux caused by gene conversion and crossing over in inversion heterokaryotypes. Genetics 146:2695–709
     [Google Scholar]
  41. 41.
    Chun S, Fay JC. 2011. Evidence for hitchhiking of deleterious mutations within the human genome. PLOS Genet. 7:8e1002240
     [Google Scholar]
  42. 42.
    Barton NH. 1995. Linkage and the limits to natural selection. Genetics 140:821–41
     [Google Scholar]
  43. 43.
    Hartfield M, Otto SP. 2011. Recombination and hitchhiking of deleterious alleles. Evolution 65:92421–34
     [Google Scholar]
  44. 44.
    Schwander T, Libbrecht R, Keller L. 2014. Supergenes and complex phenotypes. Curr. Biol. 24:7R288–94
     [Google Scholar]
  45. 45.
    Jay P, Chouteau M, Whibley A, Bastide H, Llaurens V et al. 2019. Mutation accumulation in chromosomal inversions maintains wing pattern polymorphism in a butterfly. bioRxiv. 736504. http://dx.doi.org/10.1101/736504
    [Crossref]
  46. 46.
    Küpper C, Stocks M, Risse JE, Dos Remedios N, Farrell LL et al. 2015. A supergene determines highly divergent male reproductive morphs in the ruff. Nat. Genet. 48:179–83
     [Google Scholar]
  47. 47.
    Larracuente AM, Presgraves DC. 2012. The selfish Segregation Distorter gene complex of Drosophila melanogaster. Genetics 192:133–53
     [Google Scholar]
  48. 48.
    Schimenti J. 2000. Segregation distortion of mouse t haplotypes—the molecular basis emerges. Trends Genet. 16:6240–43
     [Google Scholar]
  49. 49.
    Campos JL, Halligan DL, Haddrill PR, Charlesworth B. 2014. The relation between recombination rate and patterns of molecular evolution and variation in Drosophila melanogaster. Mol. Biol. Evol. 31:41010–28
     [Google Scholar]
  50. 50.
    Gao Z, Waggoner D, Stephens M, Ober C, Przeworski M. 2015. An estimate of the average number of recessive lethal mutations carried by humans. Genetics 199:41243–54
     [Google Scholar]
  51. 51.
    Narasimhan VM, Hunt KA, Mason D, Baker CL, Karczewski KJ et al. 2016. Health and population effects of rare gene knockouts in adult humans with related parents. Science 1320:1312–16
     [Google Scholar]
  52. 52.
    Bittles AH, Neel JV. 1994. The costs of human inbreeding and their implications for variations at the DNA level. Nat. Genet. 8:2117–21
     [Google Scholar]
  53. 53.
    Overall ADJ, Waxman D. 2020. Lethal mutations with fluctuating heterozygous effect: the lethal force of effective dominance. J. Hum. Genet. 65:121105–13
     [Google Scholar]
  54. 54.
    Farrell PM. 2008. The prevalence of cystic fibrosis in the European Union. J. Cyst. Fibros. 7:5450–53
     [Google Scholar]
  55. 55.
    Myrianthopoulos NC, Aronson SM. 1966. Population dynamics of Tay-Sachs disease. I. Reproductive fitness and selection. Am. J. Hum. Genet. 18:4313–27
     [Google Scholar]
  56. 56.
    Amorim CEG, Gao Z, Baker Z, Diesel JF, Simons YB et al. 2017. The population genetics of human disease: the case of recessive, lethal mutations. PLOS Genet. 13:9e1007499
     [Google Scholar]
  57. 57.
    Waxman D, Overall ADJ. 2020. Influence of dominance and drift on lethal mutations in human populations. Front. Genet. 11:267
     [Google Scholar]
  58. 58.
    Gao Z, Przeworski M, Sella G 2015. Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species. Evolution 69:2431–46
     [Google Scholar]
  59. 59.
    Fijarczyk A, Babik W. 2015. Detecting balancing selection in genomes: limits and prospects. Mol. Ecol. 24:143529–45
     [Google Scholar]
  60. 60.
    Lee YW, Fishman L, Kelly JK, Willis JH. 2016. A segregating inversion generates fitness variation in yellow monkeyflower (Mimulus guttatus). Genetics 202:41473–84
     [Google Scholar]
  61. 61.
    Hermisson J, Pennings PS. 2005. Soft sweeps: molecular population genetics of adaptation from standing genetic variation. Genetics 169:42335–52
     [Google Scholar]
  62. 62.
    Keightley PD, Ness RW, Halligan DL, Haddrill PR. 2014. Estimation of the spontaneous mutation rate per nucleotide site in a Drosophila melanogaster full-sib family. Genetics 196:1313–20
     [Google Scholar]
  63. 63.
    Hoensgsberg HF, Castro LE, Granobles LA, Idrobo JM. 1969. Population genetics in the American tropics. II. The comparative genetics of Drosophila in European and neo-tropical environments. Genetica 40:43–60
     [Google Scholar]
  64. 64.
    Watanabe TK. 1967. Persistence of lethal genes associated with DF in natural populations of Drosophila melanogaster. Jpn. J. Genet. 42:6375–86
     [Google Scholar]
  65. 65.
    Watanabe TK. 1969. Frequency of deleterious chromosomes and allelism between lethals genes in Japanese natural populations of Drosophila melanogaster. Jpn. J. Genet. 44:3171–87
     [Google Scholar]
  66. 66.
    Kosuda K. 1971. Synergistic interaction between second and third chromosomes on viability of Drosophila melanogaster. Jpn. J. Genet. 46:141–52
     [Google Scholar]
  67. 67.
    Band HT, Ives PT. 1963. Genetic structure of populations. I. On the nature of the genetic load in the South Amherst population of Drosophila melanogaster. Evolution 17:2198–215
     [Google Scholar]
  68. 68.
    Band HT. 1964. Genetic structure of populations. III. Natural selection and concealed genetic variability in a natural population of Drosophila melanogaster. Evolution 18:3384–404
     [Google Scholar]
  69. 69.
    Temin RG, Meyer HU, Dawson PS, Crow JF. 1969. The influence of epistasis on homozygous viability depression in Drosophila melanogaster. Genetics 61:2497–519
     [Google Scholar]
  70. 70.
    Dawood MM. 1961. The genetic load in the second chromosomes of some populations of Drosophila melanogaster in Egypt. Genetics 46:239–46
     [Google Scholar]
  71. 71.
    Ives PT, Band HT. 1986. Continuing studies on the South Amherst Drosophila melanogaster natural population during the 1970’s and 1980’s. Evolution 40:61289–302
     [Google Scholar]
  72. 72.
    Watanabe TK, Watanabe T, Oshima C. 1976. Genetic changes in natural populations of Drosophila melanogaster. Evolution 30:1109–18
     [Google Scholar]
  73. 73.
    Ives PT. 1945. The genetic structure of American populations of Drosophila melanogaster. Genetics 30:2167–96
     [Google Scholar]
  74. 74.
    Mukai T, Yamaguchi O. 1974. The genetic structure of natural populations of Drosophila melanogaster. XI. Genetic variability in a local population. Genetics 76:2339–66
     [Google Scholar]
  75. 75.
    Wallace B. 1962. Temporal changes in the roles of lethal and semilethal chromosomes within populations of Drosophila melanogaster. Am. Nat. 96:889247–56
     [Google Scholar]
  76. 76.
    Anderson WW. 1969. Genetics of natural populations XLI. The selection coefficients of heterozygotes for lethal chromosomes in Drosophila on different genetic backgrounds. Genetics 62:4827–36
     [Google Scholar]
  77. 77.
    Dobzhansky T, Spassky B. 1968. Genetics of natural populations. XL. Heterotic and deleterious effects of recessive lethals in populations of Drosophila pseudoobscura. Genetics 59:3411–25
     [Google Scholar]
  78. 78.
    Band HT. 1963. Genetic structure of populations. II. Viabilities and variances of heterozygotes in constant and fluctuating environments. Evolution 17:3307–19
     [Google Scholar]
  79. 79.
    Tobari I. 1966. Effects of temperature on the viability of heterozygotes of lethal chromosomes in Drosophila melanogaster. Genetics 53:2249–59
     [Google Scholar]
/content/journals/10.1146/annurev-animal-050422-092520
Loading
Interrogating the Roles of Mutation–Selection Balance, Heterozygote Advantage, and Linked Selection in Maintaining Recessive Lethal Variation in Natural Populations
Annual Review of Animal Biosciences 11, 77 (2023); https://doi.org/10.1146/annurev-animal-050422-092520
/content/journals/10.1146/annurev-animal-050422-092520
/content/journals/10.1146/annurev-animal-050422-092520
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error