Overdominance
More actions
Overdominance, also called heterozygote advantage, is the superiority of a heterozygote over both homozygotes at one locus.[1] In population genetics the superiority is in fitness. Natural selection then raises each allele when it is rare and holds both at a stable intermediate frequency, a protected polymorphism.[2] Plant breeders apply the word to measured characters too, when the heterozygote's value lies beyond both homozygotes.[3] Overdominance is one possible cause of heterosis, the superiority of hybrid offspring over their parents, and is sometimes miscalled heterosis.[4]
Cases at single genes include yield in tomato, seed set in an Alpine orchid and survival of malaria in people.[5][6][7] Other apparent cases often turn out to be closely linked genes with dominant alleles, a pattern called pseudo-overdominance.[8]
In Cannabis, one quantitative trait locus for thousand seed mass in a hemp mapping population shows a pattern its authors call suggestive of overdominance, among 34 agronomic loci otherwise additive or dominant.[9] In Ukrainian hemp breeding the word also covers F1 means beyond the means of the parents.[10] Genome scans have led to proposals of heterozygote advantage at some genes and at one chromosomal inversion.[11][12]
Fitness and measured characters
Plant breeders place the genotypes at a locus on one scale: the homozygotes at +a and −a, the heterozygote at d. Overdominance places d beyond either homozygote.[3] Dominance and recessivity covers the rest of that scale. Selection theory uses fitness instead, writing the fitnesses of AA, Aa and aa as 1 − s, 1 and 1 − t. Overdominance is the case where s and t are both positive.[4]
In the orchid Gymnadenia rhellicani, the heterozygote's red flowers are intermediate between black and white, while red plants set more seed than either homozygote.[6] The same outcome arises in a model under stabilising selection: a mutation that overshoots the optimum when homozygous can be favoured in a heterozygote, whose phenotype is moderated.[13] Yield in tomato and seed mass in hemp are the opposite case: overdominance for a character, measured in cultivation.[5][9]
In what Lynda Delph and John Kelly call simple overdominance, the heterozygote at one gene is fitter than either homozygote in one population and environment. In emergent overdominance the advantage shows only when fitness is averaged over populations, environments or generations, so a trial in one environment would miss it.[14]
Selection at an overdominant locus
With constant fitnesses the frequency of A settles at t/(s + t).[4] It approaches that value from any starting frequency between 0 and 1 without overshooting. A rare allele sits mostly in heterozygotes and a common one mostly in the less fit homozygotes, so each gains when it is rare and the frequency returns after any disturbance short of losing an allele.[2] H.J. Muller described balanced lethal factors in 1918, in which only the heterozygote survives. R.A. Fisher derived the equilibrium for overdominance in 1922 and J.B.S. Haldane added detail on its dynamics in 1926.[15]
| Case | Fitness of AA : Aa : aa | s | t | Equilibrium frequency of A | Load |
|---|---|---|---|---|---|
| Unequal homozygotes | 0.85 : 1 : 0.70 | 0.15 | 0.30 | 0.667 | 0.100[4] |
| Balanced lethals | 0 : 1 : 0 | 1 | 1 | 0.5 | 0.5[15] |
| Sickle-cell haemoglobin (A normal, a = S) | 0.685 : 0.763 : 0.151 | 0.102 | 0.802 | 0.887 | 0.091[16] |
Load in the last column is the segregational load of Morton, Crow and Muller (1956): the fraction by which Mendelian segregation lowers mean fitness below that of the heterozygote. An asexual population could consist entirely of heterozygotes, while an outcrossing one keeps producing homozygotes. The figure is relative and does not measure a loss. A population of aa plants that receives A alleles rises in mean relative fitness from 1 − t to 1 − st/(s + t).[17]
Inbreeding lowers mean fitness at an overdominant locus because heterozygotes grow rarer, and it does the same where the fitter allele is dominant.[18] Inbreeding depression takes up the argument between the two. In a finite population overdominance can delay fixation by genetic drift. Alan Robertson showed in 1962 that an extreme equilibrium frequency often speeds fixation instead.[19]
Overdominance is one form of balancing selection, and the two words are often used as if they were the same.[20] Under simple overdominance genotype fitnesses stay constant and only the average fitness of each allele varies with frequency. Under frequency-dependent selection the fitness of the genotypes themselves varies.[14]
A general explanation and its decline
The idea goes back to 1908, when E.M. East and G.H. Shull proposed it to account for hybrid vigour and inbreeding depression.[14][8] The word goes back to F.H. Hull in 1945.[1] Theodosius Dobzhansky later promoted overdominance as a major explanation for polymorphism in natural populations.[14]
Long-term work on maize suggested that much heterosis comes from pseudo-overdominance. Additive variance in fitness proved far larger than dominance variance, a result that favours rare deleterious alleles over overdominant loci as the main cause of inbreeding depression.[14][21]
Current assessments differ. Philip Hedrick concluded from genomic surveys that loci with heterozygote advantage are a small minority in a species, more an unusual phenomenon than a major part of adaptation.[22] Joseph Felsenstein calls overdominance very rare in nature.[16] Diamantis Sellis and colleagues argue that adaptation in diploids should often pass through short-lived balanced polymorphisms of this kind, and that only direct measurement of the fitness of each genotype can test the idea.[13] Well-understood cases usually involve intense short-term pressure from pathogens or artificial selection, with a harmful effect in homozygotes of the derived allele.[6]
Single genes with measured genotypes
In tomato, plants heterozygous for loss-of-function alleles of SINGLE FLOWER TRUSS (SFT), the gene behind the flowering hormone florigen, yielded up to 60 per cent more, in distinct genetic backgrounds and environments.[5] The effect appears only in determinate plants, whose flowering repressor SELF PRUNING is defective. In those plants one mutant copy fine-tunes florigen levels and slightly delays flowering across the shoots. The delay changes plant architecture.[23]
The red morph of G. rhellicani is heterozygous for a premature stop codon in a gene that regulates a pigment enzyme. Bees and flies prefer opposite colours, and across 281 plants red ones had the highest seed set with no difference in inflorescence survival. Neither homozygous morph suffers a deleterious effect.[6]
In people, heterozygotes for sickle-cell haemoglobin are relatively protected from dying of malaria, while homozygotes have sickle cell disease. The advantage exists only where there is malaria.[7] Mapped worldwide, the allele's frequency supports its link with malaria.[24]
Apparent overdominance
A mapped locus is a stretch of chromosome, and linked genes can imitate overdominance within it. In pseudo-overdominance, proposed by D.F. Jones in 1917, each parent carries favourable alleles at different closely linked genes, so the hybrid holds a full set and the segment behaves as one overdominant locus.[8] In sorghum, two height loci about 3 Mb apart on chromosome 7, Dw3 and qHT7.1, are in repulsion: each parent carries the tall allele at one of them. At each locus the allele for tall plants is completely dominant, yet the pair behaves as a single overdominant locus in the hybrid.[25]
Apparent overdominance also appears in maize. A yield region on chromosome 3 that looked overdominant in several mapping populations proved completely dominant once isolated in near-isogenic lines. Recombinant inbred lines of maize keep more residual heterozygosity near centromeres, which McMullen and colleagues attributed to repulsion between dominant loci where recombination is limited.[26]
Associative overdominance is a further imitation, at markers that are themselves neutral. In a finite population, linkage disequilibrium with a nearby selected locus gives a neutral marker an apparent advantage in heterozygotes, whether that locus is overdominant or carries detrimental mutations.[27] The apparent advantage always shows when the linked mutations are partially recessive. Loss of variation at the marker slows only when the selection coefficient multiplied by twice the effective population size is of order 1. Well above that, background selection speeds the loss.[28]
Overdominance in cannabis
Thousand seed mass in a hemp F2
Patrick Woods and colleagues crossed the Italian fibre cultivar Carmagnola with the Ukrainian dual-purpose cultivar USO31 and planted clones of 372 F2 lines at Fort Collins, Colorado, in 2017. Of 34 agronomic QTL, heterozygotes showed additivity or dominance at all but one, TSM.2, a locus for thousand seed mass on linkage group 5 with a LOD score of 17.22, explaining 18.16 per cent of the variance. The authors called its pattern suggestive of overdominance.[9] Read from the chart in their Supplementary Figure 4, on a normalised scale, heterozygotes at TSM.2 averaged about +0.33 and the two homozygotes about −0.33 and −0.71.[29]
The same linkage group holds a cluster of QTL, LG5.05, with a QTL in the model of every agronomic trait. The authors hypothesise that a non-synonymous SNP in a homologue of the TINY gene underlies the cluster, which still needs functional validation.[9] At that SNP, heterozygotes sit close to the Carmagnola homozygotes for the other seven traits and above both homozygotes for thousand seed mass. In the same trial thousand seed mass averaged 10.8 g in USO31, 17.2 g in Carmagnola and 17.2 g in the F1.[29] Linked genes in repulsion, as in sorghum, can produce this pattern at a mapped locus.[25]
Means of crosses
A dominance coefficient hp classes inheritance in Ukrainian hemp crosses, and Mishchenko and colleagues call values beyond 1 overdominance. In an F1 from selfed lines of the seed varieties Afina and Ionino, hp ran from 1.8 to 8.6 across the traits, with partial dominance (0.4) only for what they call technical stem length. In a cross of selfed lines of the fibre varieties Hlukhivski 51 and Nika, six traits ran from −2.3 to −6.2, which the same authors call negative overdominance.[10] The coefficient compares means, and a mean of a cross cannot separate overdominance from dominance.[1]
Genome scans
In feral, European and drug-type cannabis, 23 genes in each group combine high Tajima's D with high heterozygosity and were taken to be under balancing selection. Woods and colleagues hypothesise heterozygote advantage at stress-response genes in the feral plants, at chloroplast genes in the two domesticated groups and at MTERF9, which met the criteria in all three.[11] A chromosomal inversion on chromosome 1 occurs mostly in heterozygous form. Lynch and colleagues suggest it may be kept as a balanced polymorphism through associative overdominance.[12] Both hypotheses come from DNA sequences, with no fitness measured for any genotype.
See also
References
- ↑ 1.0 1.1 1.2 Felsenstein, J. (December 2019). Theoretical evolutionary genetics. Seattle: Department of Genome Sciences, University of Washington. pp. 411–414.
- ↑ 2.0 2.1 Felsenstein, J. (December 2019). Theoretical evolutionary genetics. Seattle: Department of Genome Sciences, University of Washington. pp. 88–91.
- ↑ 3.0 3.1 Beavis, W.; Lamkey, K.; Espinosa, K.; Mahama, A.A.; Suza, W. (2023). "Gene Effects". In Suza, W.; Lamkey, K. (eds.). Quantitative Genetics for Plant Breeding. Iowa State University Digital Press. doi:10.31274/isdup.2023.146.
- ↑ 4.0 4.1 4.2 4.3 Felsenstein, J. (December 2019). Theoretical evolutionary genetics. Seattle: Department of Genome Sciences, University of Washington. p. 85.
- ↑ 5.0 5.1 5.2 Krieger, U.; Lippman, Z.B.; Zamir, D. (2010). "The flowering gene SINGLE FLOWER TRUSS drives heterosis for yield in tomato". Nature Genetics. 42 (5): 459–463. doi:10.1038/ng.550.
- ↑ 6.0 6.1 6.2 6.3 Kellenberger, R.T.; Byers, K.J.R.P.; De Brito Francisco, R.M.; Staedler, Y.M.; LaFountain, A.M.; Schönenberger, J.; Schiestl, F.P.; Schlüter, P.M. (2019). "Emergence of a floral colour polymorphism by pollinator-mediated overdominance". Nature Communications. 10 (1) 63. doi:10.1038/s41467-018-07936-x.
- ↑ 7.0 7.1 Luzzatto, L. (2012). "Sickle cell anaemia and malaria". Mediterranean Journal of Hematology and Infectious Diseases. 4 (1) e2012065. doi:10.4084/mjhid.2012.065.
- ↑ 8.0 8.1 8.2 Mackay, I.J.; Cockram, J.; Howell, P.; Powell, W. (2021). "Understanding the classics: the unifying concepts of transgressive segregation, inbreeding depression and heterosis and their central relevance for crop breeding". Plant Biotechnology Journal. 19 (1): 26–34. doi:10.1111/pbi.13481.
- ↑ 9.0 9.1 9.2 9.3 Woods, P.; Campbell, B.J.; Nicodemus, T.J.; Cahoon, E.B.; Mullen, J.L.; McKay, J.K. (2021). "Quantitative trait loci controlling agronomic and biochemical traits in Cannabis sativa". Genetics. 219 (2) iyab099. doi:10.1093/genetics/iyab099.
- ↑ 10.0 10.1 Міщенко, С.В.; Марченко, Т.Ю.; Лавриненко, Ю.О.; Ткаченко, С.М. (2022). "Рівень прояву та успадкування селекційних ознак у міжлінійних гібридів конопель насіннєвого та волокнистого напрямів використання" [The level of expression and inheritance of breeding traits in interlinear hybrids of hemp of seed and fiber directions of economic use]. Таврійський науковий вісник (in українська) (125): 84–90. doi:10.32851/2226-0099.2022.125.12.
- ↑ 11.0 11.1 Woods, P.; Price, N.; Matthews, P.; McKay, J.K. (2023). "Genome-wide polymorphism and genic selection in feral and domesticated lineages of Cannabis sativa". G3. 13 (2) jkac209. doi:10.1093/g3journal/jkac209.
- ↑ 12.0 12.1 Lynch, R.C.; Padgitt-Cobb, L.K.; Garfinkel, A.R.; Knaus, B.J.; Hartwick, N.T.; et al. (2025). "Domesticated cannabinoid synthases amid a wild mosaic cannabis pangenome". Nature. 643 (8073): 1001–1010. doi:10.1038/s41586-025-09065-0. PMC 12286863.
- ↑ 13.0 13.1 Sellis, D.; Callahan, B.J.; Petrov, D.A.; Messer, P.W. (2011). "Heterozygote advantage as a natural consequence of adaptation in diploids". Proceedings of the National Academy of Sciences. 108 (51): 20666–20671. doi:10.1073/pnas.1114573108.
- ↑ 14.0 14.1 14.2 14.3 14.4 Delph, L.F.; Kelly, J.K. (2014). "On the importance of balancing selection in plants". New Phytologist. 201 (1): 45–56. doi:10.1111/nph.12441.
- ↑ 15.0 15.1 Felsenstein, J. (December 2019). Theoretical evolutionary genetics. Seattle: Department of Genome Sciences, University of Washington. p. 92.
- ↑ 16.0 16.1 Felsenstein, J. (December 2019). Theoretical evolutionary genetics. Seattle: Department of Genome Sciences, University of Washington. pp. 104–105.
- ↑ Felsenstein, J. (December 2019). Theoretical evolutionary genetics. Seattle: Department of Genome Sciences, University of Washington. pp. 99–101.
- ↑ Felsenstein, J. (December 2019). Theoretical evolutionary genetics. Seattle: Department of Genome Sciences, University of Washington. pp. 242–244.
- ↑ Felsenstein, J. (December 2019). Theoretical evolutionary genetics. Seattle: Department of Genome Sciences, University of Washington. p. 348.
- ↑ Charlesworth, D. (2006). "Balancing selection and its effects on sequences in nearby genome regions". PLoS Genetics. 2 (4) e64. doi:10.1371/journal.pgen.0020064.
- ↑ Charlesworth, B.; Charlesworth, D. (1999). "The genetic basis of inbreeding depression". Genetical Research. 74 (3): 329–340. doi:10.1017/S0016672399004152.
- ↑ Hedrick, P.W. (2012). "What is the evidence for heterozygote advantage selection?". Trends in Ecology & Evolution. 27 (12): 698–704. doi:10.1016/j.tree.2012.08.012.
- ↑ Jiang, K.; Liberatore, K.L.; Park, S.J.; Alvarez, J.P.; Lippman, Z.B. (2013). "Tomato yield heterosis is triggered by a dosage sensitivity of the florigen pathway that fine-tunes shoot architecture". PLoS Genetics. 9 (12) e1004043. doi:10.1371/journal.pgen.1004043.
- ↑ Piel, F.B.; Patil, A.P.; Howes, R.E.; Nyangiri, O.A.; Gething, P.W.; Williams, T.N.; Weatherall, D.J.; Hay, S.I. (2010). "Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis". Nature Communications. 1 (1) 104. doi:10.1038/ncomms1104.
- ↑ 25.0 25.1 Li, X.; Li, X.; Fridman, E.; Tesso, T.T.; Yu, J. (2015). "Dissecting repulsion linkage in the dwarfing gene Dw3 region for sorghum plant height provides insights into heterosis". Proceedings of the National Academy of Sciences. 112 (38): 11823–11828. doi:10.1073/pnas.1509229112.
- ↑ Larièpe, A.; Mangin, B.; Jasson, S.; Combes, V.; Dumas, F.; et al. (2012). "The genetic basis of heterosis: multiparental quantitative trait loci mapping reveals contrasted levels of apparent overdominance among traits of agronomical interest in maize (Zea mays L.)". Genetics. 190 (2): 795–811. doi:10.1534/genetics.111.133447.
- ↑ Ohta, T. (1971). "Associative overdominance caused by linked detrimental mutations". Genetical Research. 18 (3): 277–286. doi:10.1017/s0016672300012684.
- ↑ Zhao, L.; Charlesworth, B. (2016). "Resolving the conflict between associative overdominance and background selection". Genetics. 203 (3): 1315–1334. doi:10.1534/genetics.116.188912.
- ↑ 29.0 29.1 Woods, P.; Campbell, B.J.; Nicodemus, T.J.; Cahoon, E.B.; Mullen, J.L.; McKay, J.K. (2021). "Supplemental material for Woods et al., 2021". GSA Journals, Figshare. Supplementary Table 1 and Supplementary Figures 4 and 5. doi:10.25386/genetics.14079962.