Evolutionary Genetic Models of the Ovarian Time Bomb Hypothesis for the Evolution of Genomic Imprinting

Abstract At a small number of loci in eutherian mammals, only one of the two copies of a gene is expressed; the other is silenced. Such loci are said to be “imprinted,” with some having the maternally inherited allele inactivated and others showing paternal inactivation. Several hypotheses have been proposed to explain how such a genetic system could evolve in the face of the selective advantages of diploidy. In this study, we examine the “ovarian time bomb” hypothesis, which proposes that imprinting arose through selection for reduced risk of ovarian trophoblastic disease in females. We present three evolutionary genetic models that incorporate both this selection pressure and the effect of deleterious mutations to elucidate the conditions under which imprinting could evolve. Our findings suggest that the ovarian time bomb hypothesis can explain why some growth-enhancing genes active in early embryogenesis [e.g., mouse insulin-like growth factor 2 (Igf2)] have evolved to be maternally rather than paternally inactive and why the opposite imprinting status has evolved at some growth-inhibiting loci [e.g., mouse insulin-like growth factor 2 receptor (Igf2r)].

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The Evolution of Genomic Imprinting via Variance Minimization: An Evolutionary Genetic Model

Genetics ◽

10.1093/genetics/165.1.205 ◽

2003 ◽

Vol 165 (1) ◽

pp. 205-222

Author(s):

Anton E Weisstein ◽

Hamish G Spencer

Keyword(s):

Genomic Imprinting ◽

Genetic Model ◽

Genetic System ◽

Deleterious Mutations ◽

Variance Minimization ◽

Genetic Conflict ◽

Evolutionary Genetic ◽

The Face ◽

Alternative Hypotheses ◽

Selection For

Abstract A small number of mammalian loci exhibit genomic imprinting, in which only one copy of a gene is expressed while the other is silenced. At some such loci, the maternally inherited allele is inactivated; others show paternal inactivation. Several hypotheses have been put forward to explain how this genetic system could have evolved in the face of the selective advantages of diploidy. In this study, we examine the variance-minimization hypothesis, which proposes that imprinting arose through selection for reduced variation in levels of gene expression. We present an evolutionary genetic model incorporating both this selection pressure and deleterious mutations to elucidate the conditions under which imprinting could evolve. Our analysis implies that additional mechanisms such as genetic drift are required for imprinting to evolve from an initial nonimprinting state. Other predictions of this hypothesis do not appear to fit the available data as well as predictions for two alternative hypotheses, genetic conflict and the ovarian time bomb. On the basis of this evidence, we conclude that the variance-minimization hypothesis appears less adequate to explain the evolution of genomic imprinting.

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Understanding specialism when the jack of all trades can be the master of all

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2012.1990 ◽

2012 ◽

Vol 279 (1749) ◽

pp. 4861-4869 ◽

Cited By ~ 69

Author(s):

Susanna Remold

Keyword(s):

Habitat Use ◽

Recent Work ◽

Habitat Change ◽

Directional Selection ◽

Antagonistic Pleiotropy ◽

Disease Emergence ◽

Evolutionary Genetic ◽

The Face ◽

Genetic Mechanisms ◽

Selection For

Specialism is widespread in nature, generating and maintaining diversity, but recent work has demonstrated that generalists can be equally fit as specialists in some shared environments. This no-cost generalism challenges the maxim that ‘the jack of all trades is the master of none’, and requires evolutionary genetic mechanisms explaining the existence of specialism and no-cost generalism, and the persistence of specialism in the face of selection for generalism. Examining three well-described mechanisms with respect to epistasis and pleiotropy indicates that sign (or antagonistic) pleiotropy without epistasis cannot explain no-cost generalism and that magnitude pleiotropy without epistasis (including directional selection and mutation accumulation) cannot explain the persistence of specialism. However, pleiotropy with epistasis can explain all. Furthermore, epistatic pleiotropy may allow past habitat use to influence future use of novel environments, thereby affecting disease emergence and populations' responses to habitat change.

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Responses to divergent selection for plasma concentrations of insulin-like growth factor-1 in mice

Genetics Research ◽

10.1017/s0016672300028159 ◽

1989 ◽

Vol 53 (3) ◽

pp. 187-192 ◽

Cited By ~ 21

Author(s):

H. T. Blair ◽

S. N. McCutcheon ◽

D. D. S. Mackenzie ◽

P. D. Gluckman ◽

J. E. Ormsby ◽

...

Keyword(s):

Growth Factor ◽

Plasma Concentrations ◽

Selection Criterion ◽

Divergent Selection ◽

Correlated Response ◽

Insulin Like Growth Factor ◽

Family Selection ◽

Selection For ◽

High Control ◽

And Control

SummaryA divergent selection experiment with mice, using plasma concentrations of insulin-like growth factor-1 (IGF-1) at 42 days of age as the selection criterion, was undertaken for 7 generations. Lines were not replicated. To obtain sufficient plasma for the IGF-1 assay, blood from four individuals was volumetrically bulked to obtain a litter mean IGF-1 concentration. This necessitated the use of between family selection. Although inbreeding accumulated in a linear fashion in each of the high, control and low lines, the rates were different for each line (3·6, 1·6 and 5·3% per generation for the high, control and low lines, respectively). As a consequence, the effects of selection and inbreeding are confounded in this experiment. Divergence between the high and low lines in plasma concentrations of IGF-1 continued steadily until generation 5. In generations 6 and 7, there was a reduced degree of divergence and this contributed towards the low realized heritability value of 0.15 ± 0.12. Six-week liveweight showed a steady positive correlated response to selection for or against plasma concentrations of IGF-1 until generation 4 (high-low difference = 1·7 g = 12%). In generation 5, a substantial drop in 6-week liveweight in the low line relative to both the high and control lines occurred (high-low difference, 3·9; g, 25%). This difference was maintained until generation 7.This experiment suggests that genetic variation exists at 6 weeks of age in plasma concentrations of IGF-1 in mice. Furthermore, genetic covariation between plasma IGF-1 concentrations and liveweight at 6 weeks of age is likely to be positive. Further experiments have been initiated to examine these theories.

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Association Between Insulin-like Growth Factor-1 rs35767 Polymorphism and Type 2 Diabetes Mellitus Susceptibility: A Meta-Analysis

Frontiers in Genetics ◽

10.3389/fgene.2021.774489 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiaoli Zeng ◽

Dehua Zou ◽

Qiaodi Zeng ◽

Xiaoming Chen ◽

Yue Wei ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Growth Factor ◽

Fixed Effects ◽

Meta Analysis ◽

Genetic Models ◽

Insulin Like Growth Factor ◽

Allele Model

Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T > C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk.Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models).Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082–1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095–5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055–2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148–3.257, p = 0.013) with random effects model. After omitting Gouda’s study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I2 = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004–1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model.Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.

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Insulin-like growth factor 1 acts as an autocrine factor to improve early embryogenesis in vitro

The International Journal of Developmental Biology ◽

10.1387/ijdb.130044md ◽

2013 ◽

Vol 57 (11-12) ◽

pp. 837-844 ◽

Cited By ~ 6

Author(s):

Charmaine J. Green ◽

Margot L. Day

Keyword(s):

Growth Factor ◽

Early Embryogenesis ◽

Insulin Like Growth Factor ◽

Autocrine Factor

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GENETIC SELECTION FOR INSULIN-LIKE GROWTH FACTOR-1 IN GROWING MICE IS ASSOCIATED WITH ALTERED GROWTH

Endocrinology ◽

10.1210/endo-123-3-1690 ◽

1988 ◽

Vol 123 (3) ◽

pp. 1690-1692 ◽

Cited By ~ 27

Author(s):

Hugh T. Blair ◽

Stuart N. McCutcheon ◽

Duncan D.S. Mackenzie ◽

J. Eldon Ormsby ◽

Rafat A. Siddiqui ◽

...

Keyword(s):

Growth Factor ◽

Genetic Selection ◽

Insulin Like Growth Factor ◽

Selection For

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A note on annual variation of plasma insulin-like growth factor-I concentrations and growth rates of Jersey heifers differing in genetic merit for milk production

Animal Science ◽

10.1017/s0003356100040472 ◽

1989 ◽

Vol 48 (2) ◽

pp. 467-470 ◽

Cited By ~ 1

Author(s):

S. R. Davis ◽

V. C. Farr ◽

P. D. Gluckman ◽

B. H. Breier

Keyword(s):

Growth Factor ◽

Milk Fat ◽

Annual Variation ◽

Live Weight ◽

Insulin Like Growth Factor ◽

Genetic Merit ◽

Igf I ◽

Selection For ◽

Breed Selection ◽

Jersey Cows

A study was made of the concentration of insulin-like growth factor-l (IGF-I) in the plasma of Jersey cows differing in genetic merit for milk and milk fat production. Plasma IGF-I concentrations exhibited an annual cycle and from this study it is concluded that, in the Jersey breed, selection for increased milk and milk fat production, with the correlated responses of increases in mature live weight and live-weight gain, will not be accompanied by increased plasma IGF-I concentration.

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