The Evolution of Genomic Imprinting

Abstract In some mammalian genes, the paternally and maternally derived alleles are expressed differently: this phenomenon is called genomic imprinting. Here we study the evolution of imprinting using multivariate quantitative genetic models to examine the feasibility of the genetic conflict hypothesis. This hypothesis explains the observed imprinting patterns as an evolutionary outcome of the conflict between the paternal and maternal alleles. We consider the expression of a zygotic gene, which codes for an embryonic growth factor affecting the amount of maternal resources obtained through the placenta. We assume that the gene produces the growth factor in two different amounts depending on its parental origin. We show that genomic imprinting evolves easily if females have some probability of multiple partners. This is in conflict with the observation that not all genes controlling placental development are imprinted and that imprinting in some genes is not conserved between mice and humans. We show however that deleterious mutations in the coding region of the gene create selection against imprinting.

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Genomic imprinting of H19 and insulin-like growth factor-2 in pediatric germ cell tumors

Cancer ◽

10.1002/(sici)1097-0142(19990315)85:6<1389::aid-cncr24>3.0.co;2-v ◽

1999 ◽

Vol 85 (6) ◽

pp. 1389-1394 ◽

Cited By ~ 25

Author(s):

Julie A. Ross ◽

Peter T. Schmidt ◽

John P. Perentesis ◽

Stella M. Davies

Keyword(s):

Growth Factor ◽

Germ Cell ◽

Genomic Imprinting ◽

Germ Cell Tumors ◽

Insulin Like Growth Factor

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The human transforming growth factor alpha promoter directs transcription initiation from a single site in the absence of a TATA sequence

Molecular and Cellular Biology ◽

10.1128/mcb.8.12.5549-5554.1988 ◽

1988 ◽

Vol 8 (12) ◽

pp. 5549-5554

Author(s):

E B Jakobovits ◽

U Schlokat ◽

J L Vannice ◽

R Derynck ◽

A D Levinson

Keyword(s):

Growth Factor ◽

Transcription Initiation ◽

Transforming Growth Factor ◽

Promoter Sequence ◽

Transforming Growth Factor Alpha ◽

Sequence Motif ◽

Factor Alpha ◽

Mammalian Genes ◽

Tata Sequence ◽

The Brain

Transforming growth factor alpha (TGF-alpha) is a transformation-responsive mitogenic polypeptide that is expressed in the brain, epithelial cells, and activated macrophages. We isolated and characterized the TGF-alpha promoter and localized the 5' end of the TGF-alpha transcript to a unique position. Surprisingly, no apparent TATA box was present in the promoter sequence, suggesting that transcription from mammalian genes can initiate at unique and specific positions from promoters lacking this sequence motif.

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Deletions in the C-terminal coding region of the v-sis gene: dimerization is required for transformation

Molecular and Cellular Biology ◽

10.1128/mcb.6.4.1304-1314.1986 ◽

1986 ◽

Vol 6 (4) ◽

pp. 1304-1314

Author(s):

M Hannink ◽

M K Sauer ◽

D J Donoghue

Keyword(s):

Growth Factor ◽

Gene Product ◽

Platelet Derived Growth Factor ◽

Deletion Mutants ◽

Gene Products ◽

Coding Region ◽

Strong Connection ◽

C Terminus ◽

Its Gene ◽

Transforming Gene

The v-sis gene encodes chain B of platelet-derived growth factor. However, this gene codes for additional amino acids at both the N terminus and the C terminus of its gene product which are not present in the amino acid sequence of platelet-derived growth factor. We constructed a series of deletion mutants with deletions in the v-sis gene in order to define the C-terminal limit of the v-sis gene product which is required for transformation. Deletion mutants of the v-sis gene which encoded truncated gene products up to 57 residues shorter than the v-siswt gene product were still able to transform cells. The minimal transforming region of the v-sis gene product contained six residues fewer than were present in chain B of platelet-derived growth factor. Only 10 residues, including the sequence Cys-Lys-Cys, separated the smallest transforming gene product from the largest nontransforming gene product. These cysteine residues were also important for dimerization of the v-sis gene product, since all of the nontransforming v-sis deletions were unable to form dimers when they were analyzed under nonreducing conditions. Our results suggest that there is a strong connection between transformation and dimerization.

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Long-range RNA interaction of two sequence elements required for endonucleolytic cleavage of human insulin-like growth factor II mRNAs.

Molecular and Cellular Biology ◽

10.1128/mcb.15.1.235 ◽

1995 ◽

Vol 15 (1) ◽

pp. 235-245 ◽

Cited By ~ 38

Author(s):

W Scheper ◽

D Meinsma ◽

P E Holthuizen ◽

J S Sussenbach

Keyword(s):

Growth Factor ◽

Long Range ◽

Cleavage Site ◽

Untranslated Region ◽

Cleavage Product ◽

Coding Region ◽

Endonucleolytic Cleavage ◽

Factor Ii ◽

Sequence Elements ◽

Rna Interaction

Human insulin-like growth factor II (IGF-II) mRNAs are subject to site-specific endonucleolytic cleavage in the 3' untranslated region, leading to an unstable 5' cleavage product containing the IGF-II coding region and a very stable 3' cleavage product of 1.8 kb. This endonucleolytic cleavage is most probably the first and rate-limiting step in degradation of IGF-II mRNAs. Two sequence elements within the 3' untranslated region are required for cleavage: element I, located approximately 2 kb upstream of the cleavage site, and element II, encompassing the cleavage site itself. We have identified a stable double-stranded RNA stem structure (delta G = -100 kcal/mol [418.4 kJ/mol]) that can be formed between element I and a region downstream of the cleavage site in element II. This structure is conserved among human, rat, and mouse mRNAs. Detailed analysis of the requirements for cleavage shows that the relative position of the elements is not essential for cleavage. Furthermore, the distance between the coding region and the cleavage site does not affect the cleavage reaction. Mutational analysis of the long-range RNA-RNA interaction shows that not only the double-stranded character but also the sequence of the stable RNA stem is important for cleavage.

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Genomic imprinting and its role in ethiology of human hereditary diseases

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2004-3-8-17 ◽

2004 ◽

Vol 3 (3) ◽

pp. 8-17

Author(s):

S. A. Nazarenko

Keyword(s):

Gene Expression ◽

Genomic Imprinting ◽

Special Class ◽

Growth And Development ◽

Epigenetic Inheritance ◽

Hereditary Diseases ◽

Parental Origin ◽

Imprinted Genes ◽

Methylation Of Dna ◽

Differential Gene

Genomic imprinting is a form of non-Mendelian epigenetic inheritance that is defined by differential gene expression depending on its parental origin — maternal or paternal. It is known about 60 imprinted genes many of which effect significantly on the fetus growth and development. Methylation of DNA cytosine bases that defines the interaction of DNA and proteins identifying the modified bases and controls the gene expression through chromatin compacting-decompacting mechanism, is a main epigenetic genom modifier. Disturbances in monoallelic gene expression lead to the development of a special class of human hereditary diseases — genomic imprinting diseases.

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Placental development during early pregnancy in sheep: vascular growth and expression of angiogenic factors in maternal placenta

Reproduction ◽

10.1530/rep-09-0548 ◽

2010 ◽

Vol 140 (1) ◽

pp. 165-174 ◽

Cited By ~ 50

Author(s):

Anna T Grazul-Bilska ◽

Pawel P Borowicz ◽

Mary Lynn Johnson ◽

Megan A Minten ◽

Jerzy J Bilski ◽

...

Keyword(s):

Growth Factor ◽

Fetal Growth ◽

Early Pregnancy ◽

Vascular Development ◽

Hypoxia Inducible Factor ◽

Angiogenic Factors ◽

Placental Development ◽

Proliferating Cells ◽

Placental Angiogenesis ◽

Tissue Area

Placental vascular development (angiogenesis) is critical for placental function and thus for normal embryonic/fetal growth and development. Specific environmental factors or use of assisted reproductive techniques may result in poor placental angiogenesis, which may contribute to embryonic losses and/or fetal growth retardation. Uterine tissues were collected on days 14, 16, 18, 20, 22, 24, 26, 28, and 30 after mating and on day 10 after estrus (nonpregnant controls) to determine vascular development and expression of several factors involved in the regulation of angiogenesis in the endometrium. Compared with controls, several measurements of endometrial vascularity increased (P<0.001) including vascular labeling index (LI; proportion of proliferating cells), the tissue area occupied by capillaries, area per capillary (capillary size), total capillary circumference per unit of tissue area, and expression of factor VIII (marker of endothelial cells), but capillary number decreased (P<0.001). Compared with controls, mRNA for placental growth factor, vascular endothelial growth factor receptors, angiopoietins (ANGPT) 1 and 2, ANGPT receptorTEK, endothelial nitric oxide synthase, and hypoxia-inducible factor 1α increased (P<0.05) during early pregnancy. Vascular LI was positively correlated (P<0.05) with several measurements of vascularity and with mRNA expression of angiogenic factors. These data indicate that endometrial angiogenesis, manifested by increased vascularity and increased expression of several factors involved in the regulation of angiogenesis, is initiated very early in pregnancy. This more complete description of early placental angiogenesis may provide the foundation for determining whether placental vascular development is altered in compromised pregnancies.

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