Genetic Basis of Increased Lifespan and Postponed Senescence in Drosophila melanogaster

Limited lifespan and senescence are near-universal phenomena. These quantitative traits exhibit variation in natural populations due to the segregation of many interacting loci and from environmental effects. Due to the complexity of the genetic control of lifespan and senescence, our understanding of the genetic basis of variation in these traits is incomplete. Here, we analyzed the pattern of genetic divergence between long-lived (O) Drosophila melanogaster lines selected for postponed reproductive senescence and unselected control (B) lines. We quantified the productivity of the O and B lines and found that reproductive senescence is maternally controlled. We therefore chose 57 candidate genes that are expressed in ovaries, 49 of which have human orthologs, and assessed the effects of RNA interference in ovaries and accessary glands on lifespan and reproduction. All but one candidate gene affected at least one life history trait in one sex or productivity week. In addition, 23 genes had antagonistic pleiotropic effects on lifespan and productivity. Identifying evolutionarily conserved genes affecting increased lifespan and delayed reproductive senescence is the first step toward understanding the evolutionary forces that maintain segregating variation at these loci in nature and may provide potential targets for therapeutic intervention to delay senescence while increasing lifespan.

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Genetic basis of offspring number and body weight variation in Drosophila melanogaster

10.1101/2020.07.14.203406 ◽

2020 ◽

Author(s):

Jamilla Akhund-Zade ◽

Shraddha Lall ◽

Erika Gajda ◽

Denise Yoon ◽

Benjamin de Bivort

Keyword(s):

Drosophila Melanogaster ◽

Life History ◽

Egg Production ◽

Genetic Basis ◽

Resource Constraints ◽

Adult Stage ◽

Life History Trait ◽

Functional Roles ◽

Offspring Number ◽

Weight Variation

AbstractDrosophila melanogaster egg production, a proxy for fecundity, is an extensively studied life-history trait with a strong genetic basis. As eggs develop into larvae and adults, space and resource constraints can put pressure on the developing offspring, leading to a decrease in viability, body size, and lifespan. Our goal was to map the genetic basis of offspring number and weight under the restriction of a standard laboratory vial. We screened 143 lines from the Drosophila Genetic Reference Panel for offspring numbers and weights to create an ‘offspring index’ that captured the number vs. weight trade-off. We found 30 associated variants in 18 genes. Validation of hid, Sox21b, CG8312, and mub candidate genes using gene disruption mutants demonstrated a role in adult stage viability, while mutations in Ih and Rbp increased offspring number and increased weight, respectively. The polygenic basis of offspring number and weight, with many variants of small effect, as well as the involvement of genes with varied functional roles, support the notion of Fisher’s “infinitesimal model” for this life-history trait.

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The Genetic Basis of Resistance to Diazinon in Natural Populations of Drosophila melanogaster

Genetica ◽

10.1023/b:gene.0000019920.71944.2b ◽

2004 ◽

Vol 121 (1) ◽

pp. 13-24 ◽

Cited By ~ 21

Author(s):

Fiona M. Pyke ◽

Michael R. Bogwitz ◽

Trent Perry ◽

Adrian Monk ◽

Philip Batterham ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Genetic Basis ◽

Natural Populations

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Genetic basis of offspring number-body weight tradeoff in Drosophila melanogaster

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab129 ◽

2021 ◽

Author(s):

Jamilla Akhund-Zade ◽

Shraddha Lall ◽

Erika Gajda ◽

Denise Yoon ◽

Julien F Ayroles ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Life History ◽

Egg Production ◽

Genetic Basis ◽

Resource Constraints ◽

Adult Stage ◽

Life History Trait ◽

Functional Roles ◽

Offspring Number ◽

Drosophila Genetic Reference Panel

Abstract Drosophila melanogaster egg production, a proxy for fecundity, is an extensively studied life-history trait with a strong genetic basis. As eggs develop into larvae and adults, space and resource constraints can put pressure on the developing offspring, leading to a decrease in viability, body size, and lifespan. Our goal was to map the genetic basis of offspring number and weight under the restriction of a standard laboratory vial. We screened 143 lines from the Drosophila Genetic Reference Panel for offspring numbers and weights to create an ‘offspring index’ that captured the number vs. weight trade-off. We found 18 genes containing 30 variants associated with variation in the offspring index. Validation of hid, Sox21b, CG8312, and mub candidate genes using gene disruption mutants demonstrated a role in adult stage viability, while mutations in Ih and Rbp increased offspring number and increased weight, respectively. The polygenic basis of offspring number and weight, with many variants of small effect, as well as the involvement of genes with varied functional roles, support the notion of Fisher’s “infinitesimal model” for this life-history trait.

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The lack of recombination drives the fixation of transposable elements on the fourth chromosome of Drosophila melanogaster

Genetics Research ◽

10.1017/s0016672304006755 ◽

2004 ◽

Vol 83 (2) ◽

pp. 91-100 ◽

Cited By ~ 31

Author(s):

CAROLINA BARTOLOMÉ ◽

XULIO MASIDE

Keyword(s):

Drosophila Melanogaster ◽

Irreversible Process ◽

Natural Populations ◽

Fourth Chromosome ◽

Evolutionary Forces ◽

Slightly Deleterious Mutations ◽

Nucleotide Divergence ◽

Suppressed Recombination ◽

Low Levels

In regions of suppressed recombination, where selection is expected to be less efficient in removing slightly deleterious mutations, transposable element (TE) insertions should be more likely to drift to higher frequencies, and even to reach fixation. In the absence of excision events, once a TE is fixed it cannot be eliminated from the population, and accumulation of elements thus should become an irreversible process. In the long term, this can drive the degeneration of large non-recombining fractions of the genomes. Chromosome 4 of Drosophila melanogaster has very low levels of recombination, if any, and this could be causing its degeneration. Here we report the results of a PCR-based analysis of the population frequencies of TE insertions in a sample from three African natural populations. We investigated 27 insertions from 12 TE families, located in regions of either suppressed or free recombination. Our results suggest that TE insertions tend to be fixed in the non-recombining regions, particularly on the fourth chromosome. We have also found that this involves all types of elements, and that fixed insertions are significantly shorter and more divergent from the canonical sequence than those segregating in the sample (28·1% vs. 86·3% of the canonical length, and average nucleotide divergence (DXY)=0·082 vs. 0·008, respectively). Finally, DNA-based elements seem to show a greater tendency to reach fixation than retrotransposons. Implications of these findings for the population dynamics of TEs, and the evolutionary forces that shape the patterns of genetic variation in regions of reduced recombination, are discussed.

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Spontaneous mutation for a quantitative trait in Drosophila melanogaster. II. Distribution of mutant effects on the trait and fitness

Genetics Research ◽

10.1017/s0016672300031220 ◽

1993 ◽

Vol 61 (2) ◽

pp. 117-126 ◽

Cited By ~ 45

Author(s):

Marí A. López ◽

Carlos López-Fanjul

Keyword(s):

Drosophila Melanogaster ◽

Large Fraction ◽

Spontaneous Mutation ◽

Natural Populations ◽

Recessive Gene ◽

Considerable Effect ◽

Pleiotropic Effects ◽

Standing Variation ◽

Bristle Number ◽

B Lines

SummaryStarting from a completely homozygous population of Drosophila melanogaster, lines have been derived and subjected to 47 generations of divergent selection for abdominal bristle number (20 lines selected in each direction) or to 60–67 generations of inbreeding (100 B lines maintained by a single brother-sister mating, 100 C lines maintained by two double first cousin ma tings). In the selected lines, 25 were identified carrying at least 30 mutations affecting bristle number. A large fraction of these mutations (42 %) were lethals. Non-lethal mutations had smaller effects on the trait, were predominantly additive and had no detectable pleiotropic effects on fitness. In the inbred lines, 21 mutations affecting bristles were individually analysed. Deleterious mutations had the largest effects on the trait (irrespective of sign) and showed recessive gene action (complete or incomplete). The rest were predominantly additive and had smaller effects. Thus, both procedures identify a quasi-neutral class of additive mutations which should be close to that responsible for standing variation in natural populations. Moreover, the results indicate a leptokurtic distribution of mutant effects, consistent with a model of natural selection acting on bristles through pleiotropic effects of pertinent loci on fitness. Consequently, neutral additive alleles of considerable effect can be found segregating at intermediate frequencies in natural populations.

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Quantitative Trait Loci Responsible for Variation in Sexually Dimorphic Traits in Drosophila melanogaster

Genetics ◽

10.1093/genetics/163.2.771 ◽

2003 ◽

Vol 163 (2) ◽

pp. 771-787 ◽

Cited By ~ 5

Author(s):

Artyom Kopp ◽

Rita M Graze ◽

Shizhong Xu ◽

Sean B Carroll ◽

Sergey V Nuzhdin

Keyword(s):

Drosophila Melanogaster ◽

Genetic Variation ◽

Quantitative Trait Loci ◽

Quantitative Trait ◽

Genetic Basis ◽

Morphological Evolution ◽

Recombinant Inbred Lines ◽

Natural Populations ◽

Sexually Dimorphic ◽

Trait Loci

Abstract To understand the mechanisms of morphological evolution and species divergence, it is essential to elucidate the genetic basis of variation in natural populations. Sexually dimorphic characters, which evolve rapidly both within and among species, present attractive models for addressing these questions. In this report, we map quantitative trait loci (QTL) responsible for variation in sexually dimorphic traits (abdominal pigmentation and the number of ventral abdominal bristles and sex comb teeth) in a natural population of Drosophila melanogaster. To capture the pattern of genetic variation present in the wild, a panel of recombinant inbred lines was created from two heterozygous flies taken directly from nature. High-resolution mapping was made possible by cytological markers at the average density of one per 2 cM. We have used a new Bayesian algorithm that allows QTL mapping based on all markers simultaneously. With this approach, we were able to detect small-effect QTL that were not evident in single-marker analyses. Our results show that at least for some sexually dimorphic traits, a small number of QTL account for the majority of genetic variation. The three strongest QTL account for >60% of variation in the number of ventral abdominal bristles. Strikingly, a single QTL accounts for almost 60% of variation in female abdominal pigmentation. This QTL maps to the chromosomal region that Robertson et al. have found to affect female abdominal pigmentation in other populations of D. melanogaster. Using quantitative complementation tests, we demonstrate that this QTL is allelic to the bric a brac gene, whose expression has previously been shown to correlate with interspecific differences in pigmentation. Multiple bab alleles that confer distinct phenotypes appear to segregate in natural populations at appreciable frequencies, suggesting that intraspecific and interspecific variation in abdominal pigmentation may share a similar genetic basis.

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Apoptosis and development

Essays in Biochemistry ◽

10.1042/bse0390011 ◽

2003 ◽

Vol 39 ◽

pp. 11-24 ◽

Cited By ~ 6

Author(s):

Justin V McCarthy

Keyword(s):

Drosophila Melanogaster ◽

Mammalian Cells ◽

Cell Number ◽

Model Organisms ◽

Biological Processes ◽

Nematode Caenorhabditis Elegans ◽

Apoptotic Pathway ◽

Genetic Pathways ◽

Evolutionarily Conserved ◽

Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

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