scholarly journals Wild worm embryogenesis harbors ubiquitous polygenic modifier variation

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Annalise B Paaby ◽  
Amelia G White ◽  
David D Riccardi ◽  
Kristin C Gunsalus ◽  
Fabio Piano ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Gene Function ◽  
Natural Populations ◽  
Complex Trait ◽  
Genetic Modifiers ◽  
Wild Type ◽  
Cryptic Genetic Variation ◽  
Quantitative Genetic ◽  
In The Wild

Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of Caenorhabditis elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality. Each perturbation revealed CGV, indicating that wild-type genomes harbor myriad genetic modifiers that may have little effect individually but which in aggregate can dramatically influence penetrance. Phenotypes were mediated by many modifiers, indicating high polygenicity, but the alleles tend to act very specifically, indicating low pleiotropy. Our findings demonstrate the extent of conditional functionality in complex trait architecture.

scholarly journals C. elegansharbors pervasive cryptic genetic variation for embryogenesis

2014 ◽  
Author(s):  
Annalise Paaby ◽  
Amelia White ◽  
David Riccardi ◽  
Kristin Gunsalus ◽  
Fabio Piano ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Gene Networks ◽  
Genetic Basis ◽  
Disease Susceptibility ◽  
Disease Risk ◽  
Natural Populations ◽  
Cryptic Genetic Variation ◽  
Natural Genetic Variation ◽  
C Elegans ◽  
In The Wild

Conditionally functional mutations are an important class of natural genetic variation, yet little is known about their prevalence in natural populations or their contribution to disease risk. Here, we describe a vast reserve of cryptic genetic variation, alleles that are normally silent but which affect phenotype when the function of other genes is perturbed, in the gene networks ofC. elegansembryogenesis. We find evidence that cryptic-effect loci are ubiquitous and segregate at intermediate frequencies in the wild. The cryptic alleles demonstrate low developmental pleiotropy, in that specific, rather than general, perturbations are required to reveal them. Our findings underscore the importance of genetic background in characterizing gene function and provide a model for the expression of conditionally functional effects that may be fundamental in basic mechanisms of trait evolution and the genetic basis of disease susceptibility.

scholarly journals UNEQUAL CROSSING OVER AT THE rRNA TANDON AS A SOURCE OF QUANTITATIVE GENETIC VARIATION IN DROSOPHILA

Genetics ◽  
1980 ◽  
Vol 95 (3) ◽  
pp. 727-742 ◽  
Author(s):  
R Frankham ◽  
D A Briscoe ◽  
R K Nurthen
Keyword(s):  
Genetic Variation ◽  
Selection Response ◽  
Crossing Over ◽  
Wild Type ◽  
X Chromosomes ◽  
Unequal Crossing Over ◽  
Quantitative Genetic ◽  
Y Chromosomes ◽  
Homozygous Line ◽  
Minimum Estimate

ABSTRACT Abdominal bristle selection lines (three high and three low) and controls were founded from a marked homozygous line to measure the contribution of sex-linked "mutations" to selection response. Two of the low lines exhibited a period of rapid response to selection in females, but not in males. There were corresponding changes in female variance, in heritabilities in females, in the sex ratio (a deficiency of females) and in fitness, as well as the appearance of a mutant phenotype in females of one line. All of these changes were due to bb alleles (partial deficiencies for the rRNA tandon) in the X chromosomes of these lines, while the Y chromosomes remained wild-type bb+. We argue that the bb alleles arose by unequal crossing over in the rRNA tandon.—A prediction of this hypothesis is that further changes can occur in the rRNA tandon as selection is continued. This has now been shown to occur.—Our minimum estimate of the rate of occurrence of changes at the rRNA tandon is 3 × 10-4. As this is substantially higher than conventional mutation rates, the questions of the mechanisms and rates of origin of new quantitative genetic variation require careful re-examination.

scholarly journals H3K9me2 protects lifespan against the transgenerational burden of germline transcription in C. elegans

2019 ◽  
Author(s):  
Teresa W. Lee ◽  
Heidi S. David ◽  
Amanda K. Engstrom ◽  
Brandon S. Carpenter ◽  
David J. Katz
Keyword(s):  
Caenorhabditis Elegans ◽  
Histone H3 ◽  
Complex Trait ◽  
Wild Type ◽  
C Elegans ◽  
Germline Transcription ◽  
Active Transcription

ABSTRACTDuring active transcription, the COMPASS complex methylates histone H3 at lysine 4 (H3K4me). In Caenorhabditis elegans, mutations in COMPASS subunits, including WDR-5, extend lifespan and enable the inheritance of increased lifespan in wild-type descendants. Here we show that the increased lifespan of wdr-5 mutants is itself a transgenerational trait that manifests after eighteen generations and correlates with changes in the heterochromatin factor H3K9me2. Additionally, we find that wdr-5 mutant longevity and its inheritance requires the H3K9me2 methyltransferase MET-2 and can be recapitulated by a mutation in the putative H3K9me2 demethylase JHDM-1. These data suggest that lifespan is constrained by reduced H3K9me2 due to transcription-coupled H3K4me. wdr-5 mutants alleviate this burden, extending lifespan and enabling the inheritance of increased lifespan. Thus, H3K9me2 functions in the epigenetic establishment and inheritance of a complex trait. Based on this model, we propose that lifespan is limited by the germline in part because germline transcription reduces heterochromatin.

scholarly journals Layers of Cryptic Genetic Variation Underlie a Yeast Complex Trait

Genetics ◽  
2019 ◽  
Vol 211 (4) ◽  
pp. 1469-1482 ◽  
Author(s):  
Jonathan T. Lee ◽  
Alessandro L. V. Coradini ◽  
Amy Shen ◽  
Ian M. Ehrenreich
Keyword(s):  
Genetic Variation ◽  
Complex Trait ◽  
Cryptic Genetic Variation

scholarly journals A quantitative genetic analysis of fitness and its components in Drosophila melanogaster

1986 ◽  
Vol 47 (1) ◽  
pp. 59-70 ◽  
Author(s):  
Trudy F. C. Mackay
Keyword(s):  
Drosophila Melanogaster ◽  
Natural Populations ◽  
Strongly Correlated ◽  
Wild Type ◽  
Relative Contribution ◽  
Quantitative Characters ◽  
Quantitative Genetic ◽  
Bristle Number ◽  
Metric Traits ◽  
Average Fitness

SummaryForty-one third chromosomes extracted from a natural population of Drosophila melanogaster were assessed for net fitness and for the quantitative characters viability, net fertility, female productivity, male weight, abdominal bristle number, and sternopleural bristle number. Net homozygous and heterozygous fitness of the third chromosomes was estimated by competition against a marked balancer third chromosome. Average fitness of the homozygous lines relative to wild-type heterozygotes was 0·13, indicating substantial inbreeding depression for net fitness. All significant correlations of quantitative characters with fitness and with each other were high and positive. Homozygous fitness is strongly correlated with net fertility, viability, and female productivity, moderately associated with male weight, and not significantly associated with bristle traits. The combination of metric traits which best predicts homozygous fitness is the simple multiple of viability and female productivity. Heterozygous fitness is not correlated with homozygous fitness; furthermore, the relative contribution of metric traits to fitness in a heterozygous population is likely to be different from that deduced from homozygous lines. These observations are consistent with a model of genetic variation for fitness in natural populations caused by segregation of rare deleterious recessive alleles.

scholarly journals Genetic variation affecting heart rate in Drosophila melanogaster

1999 ◽  
Vol 74 (2) ◽  
pp. 121-128 ◽  
Author(s):  
J. ROBBINS ◽  
R. AGGARWAL ◽  
R. NICHOLS ◽  
G. GIBSON
Keyword(s):  
Heart Rate ◽  
Drosophila Melanogaster ◽  
Heart Function ◽  
Susceptibility Gene ◽  
Natural Populations ◽  
Model Organism ◽  
Genetic Dissection ◽  
Wild Type ◽  
Quantitative Genetic ◽  
Wide Range

Heart rate in pre-pupae of Drosophila melanogaster is shown to vary over a wide range from 2·5 to 3·7 beats per second. Quantitative genetic analysis of a sample of 11 highly inbred lines indicates that approaching one-quarter of the total variance in natural populations can be attributed to genetic differences between flies. A hypomorphic allele of the potassium channel gene ether-a-gogo, which is homologous to a human long-QT syndrome susceptibility gene (HERG), has a heart rate at the low end of the wild-type range, but this effect can be suppressed in certain wild-type genetic backgrounds. This study provides a baseline for investigation of pharmacological and other physiological influences on heart rate in the model organism, and implies that quantitative genetic dissection will provide insight into the molecular basis for variation in normal and arrhythmic heart function.

scholarly journals Cryptic Genetic Variation in Natural Populations: A Predictive Framework

2014 ◽  
Vol 54 (5) ◽  
pp. 783-793 ◽  
Author(s):  
C. C. Ledon-Rettig ◽  
D. W. Pfennig ◽  
A. J. Chunco ◽  
I. Dworkin
Keyword(s):  
Genetic Variation ◽  
Natural Populations ◽  
Cryptic Genetic Variation

scholarly journals Quantitative genetic variation of enzyme activities in natural populations of Drosophila melanogaster

1980 ◽  
Vol 77 (2) ◽  
pp. 1073-1077 ◽  
Author(s):  
C. C. Laurie-Ahlberg ◽  
G. Maroni ◽  
G. C. Bewley ◽  
J. C. Lucchesi ◽  
B. S. Weir
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Variation ◽  
Enzyme Activities ◽  
Natural Populations ◽  
Quantitative Genetic

scholarly journals Multiple layers of cryptic genetic variation underlie a yeast complex trait

2018 ◽  
Author(s):  
Jonathan T Lee ◽  
Alessandro L V Coradini ◽  
Amy Shen ◽  
Ian M Ehrenreich
Keyword(s):  
Genetic Variation ◽  
Complex Trait ◽  
Environment Interaction ◽  
Coding Region ◽  
Cryptic Genetic Variation ◽  
Genotype Environment Interaction ◽  
Genetic Perturbations ◽  
In Cis ◽  
The Relationship ◽  
Surface Gene

Cryptic genetic variation may be an important contributor to heritable traits, but its extent and regulation are not fully understood. Here, we investigate the cryptic genetic variation underlying a Saccharomyces cerevisiae colony phenotype that is typically suppressed in a cross of the lab strain BY4716 (BY) and a derivative of the clinical isolate 322134S (3S). To do this, we comprehensively map the trait's genetic basis in the BYx3S cross in the presence of three different genetic perturbations that enable its expression. This allows us to detect and compare the specific loci harboring cryptic genetic variants that interact with each perturbation. In total, we identify 21 loci, all but one of which interacts with just a subset of the perturbations. Beyond impacting which loci contribute to the trait, the genetic perturbations also influence the extent of additivity, epistasis, and genotype-environment interaction among the detected loci. Additionally, we show that the single locus interacting with all three perturbations corresponds to the coding region of the cell surface gene FLO11. Nearly all of the other loci influence FLO11 transcription in cis or trans. However, the perturbations reveal cryptic genetic variation in different pathways and sub-pathways upstream of FLO11, suggesting that multiple layers of cryptic genetic variation with highly contextual effects underlie the trait. Our work demonstrates an abundance of cryptic genetic variation in transcriptional regulation and illustrates how this cryptic genetic variation complicates efforts to study the relationship between genotype and phenotype.

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