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Transgenerational inheritance of diet-induced genome rearrangements in Drosophila.

Aldrich JC, Maggert KA - PLoS Genet. (2015)

Bottom Line: Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction.Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process.Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenerationally heritable.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, College of Science, Texas A&M University, College Station, Texas, United States of America.

ABSTRACT
Ribosomal RNA gene (rDNA) copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila genome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction. Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process. Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenerationally heritable. This finding explains one source of natural rDNA copy number variation revealing a clear long-term consequence of diet.

No MeSH data available.


Related in: MedlinePlus

Adult diet changes rDNA copy number of progeny.(A) Crossing scheme used to genetically isolate Y-linked rDNA arrays for quantitative real-time PCR analysis. DNA was extracted from female progeny. C(1)DX has no rDNA (rDNA0), X and Y chromosomes initially have normal complements of rDNA (rDNA+), and effects of diet are assessed on the patroclinous Y-linked rNA (rDNA*) Numbers ((1) and (2)) are referred to in the main text. (B)Y-linked rDNA copy number of the progeny of males raised on SY10 or SY30 as larvae. Percentages calculated relative to the progeny of males raised on Standard (Std) food, defined as 100% (gray bar). N = 3 pools each of 20 larvae for each condition. (C) Crossing scheme used to treat and isolate Y-linked rDNA arrays for analysis. “Control” flies were derived from freshly-eclosed males mated to C(1)DX females and raised entirely on Standard food, and dietary-manipulated flies were derived from crosses of the same males after brooding on different food sources (see text, including references to (3)-(6)) then outcrossed to C(1)DX females and the progeny raised entirely on Standard food. (D)Y-linked rDNA copy number of progeny of adult males kept for 20 days on SY10, SY30, or Standard food with or without 10 μM Rapamycin. Percentages calculated relative to the progeny of males mated prior to the 20-day treatment (“Control” in (C)). Error bars are standard deviation of three independent biological replicates each of ten sibling females. P-values calculated using Student’s t-test.
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pgen.1005148.g005: Adult diet changes rDNA copy number of progeny.(A) Crossing scheme used to genetically isolate Y-linked rDNA arrays for quantitative real-time PCR analysis. DNA was extracted from female progeny. C(1)DX has no rDNA (rDNA0), X and Y chromosomes initially have normal complements of rDNA (rDNA+), and effects of diet are assessed on the patroclinous Y-linked rNA (rDNA*) Numbers ((1) and (2)) are referred to in the main text. (B)Y-linked rDNA copy number of the progeny of males raised on SY10 or SY30 as larvae. Percentages calculated relative to the progeny of males raised on Standard (Std) food, defined as 100% (gray bar). N = 3 pools each of 20 larvae for each condition. (C) Crossing scheme used to treat and isolate Y-linked rDNA arrays for analysis. “Control” flies were derived from freshly-eclosed males mated to C(1)DX females and raised entirely on Standard food, and dietary-manipulated flies were derived from crosses of the same males after brooding on different food sources (see text, including references to (3)-(6)) then outcrossed to C(1)DX females and the progeny raised entirely on Standard food. (D)Y-linked rDNA copy number of progeny of adult males kept for 20 days on SY10, SY30, or Standard food with or without 10 μM Rapamycin. Percentages calculated relative to the progeny of males mated prior to the 20-day treatment (“Control” in (C)). Error bars are standard deviation of three independent biological replicates each of ten sibling females. P-values calculated using Student’s t-test.

Mentions: Wild-caught Drosophila strains exhibit a wide variance in rDNA copy number [34, 35]; the source of this variance, however, is unknown. For this variability to be explained by environmentally induced instability during the life history of these chromosomes, germline rDNA would have to be susceptible to environmental influence. To look for possible germline effects of diet, we used a genetic strategy to specifically measure copy number of Y-linked rDNA. We chose to focus our attention on the Y-linked array because it is preferentially active in males [43, 71] and because of the ease with which the Y chromosome is manipulated genetically [55]. We genetically-isolated Y-linked rDNA arrays by crossing adult males to females bearing an rDNA-deficient compound X chromosome (C(1)DX) (Fig 5A). Female progeny of this cross were viable and carried the patroclinous Y-linked rDNA as their sole source of rRNA genes; any differences between rDNA in daughters were due to permanent germline changes to the chromosomes occurring in the fathers.


Transgenerational inheritance of diet-induced genome rearrangements in Drosophila.

Aldrich JC, Maggert KA - PLoS Genet. (2015)

Adult diet changes rDNA copy number of progeny.(A) Crossing scheme used to genetically isolate Y-linked rDNA arrays for quantitative real-time PCR analysis. DNA was extracted from female progeny. C(1)DX has no rDNA (rDNA0), X and Y chromosomes initially have normal complements of rDNA (rDNA+), and effects of diet are assessed on the patroclinous Y-linked rNA (rDNA*) Numbers ((1) and (2)) are referred to in the main text. (B)Y-linked rDNA copy number of the progeny of males raised on SY10 or SY30 as larvae. Percentages calculated relative to the progeny of males raised on Standard (Std) food, defined as 100% (gray bar). N = 3 pools each of 20 larvae for each condition. (C) Crossing scheme used to treat and isolate Y-linked rDNA arrays for analysis. “Control” flies were derived from freshly-eclosed males mated to C(1)DX females and raised entirely on Standard food, and dietary-manipulated flies were derived from crosses of the same males after brooding on different food sources (see text, including references to (3)-(6)) then outcrossed to C(1)DX females and the progeny raised entirely on Standard food. (D)Y-linked rDNA copy number of progeny of adult males kept for 20 days on SY10, SY30, or Standard food with or without 10 μM Rapamycin. Percentages calculated relative to the progeny of males mated prior to the 20-day treatment (“Control” in (C)). Error bars are standard deviation of three independent biological replicates each of ten sibling females. P-values calculated using Student’s t-test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4401788&req=5

pgen.1005148.g005: Adult diet changes rDNA copy number of progeny.(A) Crossing scheme used to genetically isolate Y-linked rDNA arrays for quantitative real-time PCR analysis. DNA was extracted from female progeny. C(1)DX has no rDNA (rDNA0), X and Y chromosomes initially have normal complements of rDNA (rDNA+), and effects of diet are assessed on the patroclinous Y-linked rNA (rDNA*) Numbers ((1) and (2)) are referred to in the main text. (B)Y-linked rDNA copy number of the progeny of males raised on SY10 or SY30 as larvae. Percentages calculated relative to the progeny of males raised on Standard (Std) food, defined as 100% (gray bar). N = 3 pools each of 20 larvae for each condition. (C) Crossing scheme used to treat and isolate Y-linked rDNA arrays for analysis. “Control” flies were derived from freshly-eclosed males mated to C(1)DX females and raised entirely on Standard food, and dietary-manipulated flies were derived from crosses of the same males after brooding on different food sources (see text, including references to (3)-(6)) then outcrossed to C(1)DX females and the progeny raised entirely on Standard food. (D)Y-linked rDNA copy number of progeny of adult males kept for 20 days on SY10, SY30, or Standard food with or without 10 μM Rapamycin. Percentages calculated relative to the progeny of males mated prior to the 20-day treatment (“Control” in (C)). Error bars are standard deviation of three independent biological replicates each of ten sibling females. P-values calculated using Student’s t-test.
Mentions: Wild-caught Drosophila strains exhibit a wide variance in rDNA copy number [34, 35]; the source of this variance, however, is unknown. For this variability to be explained by environmentally induced instability during the life history of these chromosomes, germline rDNA would have to be susceptible to environmental influence. To look for possible germline effects of diet, we used a genetic strategy to specifically measure copy number of Y-linked rDNA. We chose to focus our attention on the Y-linked array because it is preferentially active in males [43, 71] and because of the ease with which the Y chromosome is manipulated genetically [55]. We genetically-isolated Y-linked rDNA arrays by crossing adult males to females bearing an rDNA-deficient compound X chromosome (C(1)DX) (Fig 5A). Female progeny of this cross were viable and carried the patroclinous Y-linked rDNA as their sole source of rRNA genes; any differences between rDNA in daughters were due to permanent germline changes to the chromosomes occurring in the fathers.

Bottom Line: Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction.Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process.Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenerationally heritable.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, College of Science, Texas A&M University, College Station, Texas, United States of America.

ABSTRACT
Ribosomal RNA gene (rDNA) copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila genome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction. Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process. Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenerationally heritable. This finding explains one source of natural rDNA copy number variation revealing a clear long-term consequence of diet.

No MeSH data available.


Related in: MedlinePlus