scholarly journals Sex-biased gene expression in Drosophila melanogaster is constrained by ontogeny and genetic architecture

2016 ◽  
Author(s):  
Fiona C Ingleby ◽  
Claire L Webster ◽  
Tanya M Pennell ◽  
Ilona Flis ◽  
Edward H Morrow

Sexual dimorphism is predicted to be constrained by the underlying genetic architecture shared between the sexes and through ontogeny, but whole-transcriptome data for both sexes across genotypes and developmental stages are lacking. Within a quantitative genetic framework, we sequenced RNA from Drosophila melanogaster at different developmental stages to examine sex-biased gene expression and how selection acts upon it. We found evidence that gene expression is constrained by both univariate and multivariate shared genetic variation between genes, sexes and developmental stages, but may be resolved by differential splicing. These results provide a comprehensive picture of how conflict over sexual dimorphism varies through development and clarifies the conditions under which it is predicted to evolve.

Genetics ◽  
1988 ◽  
Vol 119 (2) ◽  
pp. 421-433
Author(s):  
D E Cowley ◽  
W R Atchley

Abstract A quantitative genetic analysis is reported for traits on the head and thorax of adult fruit flies, Drosophila melanogaster. Females are larger than males, and the magnitude of sexual dimorphism is similar for traits derived from the same imaginal disc, but the level of sexual dimorphism varies widely across discs. The greatest difference between males and females occurs for the dimensions of the sclerotized mouthparts of the proboscis. Most of the traits studied are highly heritable with heritabilities ranging from 0.26 to 0.84 for males and 0.27 to 0.81 for females. In general, heritabilities are slightly higher for males, possibly reflecting the effect of dosage compensation on X-linked variance. The X chromosome contributes substantially to variance for many of these traits, and including results reported elsewhere, the variance for over two-thirds of the traits studied includes X-linked variance. The genetic correlations between sexes for the same trait are generally high and close to unity. Coupled with the small differences in the traits between sexes for heritabilities and phenotypic variances, these results suggest that selection would be very slow to change the level of sexual dimorphism in size of various body parts.


2021 ◽  
Author(s):  
Amardeep Singh ◽  
Aneil F. Agrawal

AbstractIn most species, selection favours different phenotypes in the two sexes. This type of sexual antagonism can be resolved through the evolution of sexual dimorphism. Sex differences in gene regulation is a proximate mechanism by which this resolution can be achieved. One form of differential gene regulation is sex differences in the amount a gene is expressed, so called sex-biased gene expression (SBGE). Less attention has been given to sexual dimorphism in isoform usage (SDIU), resulting from sex-specific alternative splicing, which may be another way in which conflict between the sexes is resolved. Here, we use RNA-seq data from two tissue types (heads and bodies) from 18 genotypes of adult Drosophila melanogaster to investigate SDIU. In our data, SBGE and SDIU are both much more prevalent in the body than the head. SDIU is less common among sex-biased than unbiased genes in the body, though the opposite pattern occurs in the head. SDIU, but not SBGE, is significantly associated with reduced values of Tajima’s D, possibly indicating that such genes experience positive selection more frequently. SBGE, but not SDIU, is associated with increased πN/πS, possibly indicating weaker purifying selection. Together, these results are consistent with the idea that the SDIU and SBGE are alternative pathways towards the resolution of conflict between the sexes with distinct evolutionary consequences.


2020 ◽  
Author(s):  
Wen Huang ◽  
Mary Anna Carbone ◽  
Richard F. Lyman ◽  
Robert H. H. Anholt ◽  
Trudy F. C. Mackay

AbstractThe genetics of phenotypic responses to changing environments remains elusive. Using whole genome quantitative gene expression as a model, we studied how the genetic architecture of regulatory variation in gene expression changed in a population of fully sequenced inbred Drosophila melanogaster strains when flies developed at different environments (25 °C and 18 °C). We found a substantial fraction of the transcriptome exhibited genotype by environment interaction, implicating environmentally plastic genetic architecture of gene expression. Genetic variance in expression increased at 18 °C relative to 25 °C for most genes that had a change in genetic variance. Although the majority of expression quantitative trait loci (eQTLs) for the gene expression traits in the two environments were shared and had similar effects, analysis of the environment-specific eQTLs revealed enrichment of binding sites for two transcription factors. Finally, although genotype by environment interaction in gene expression could potentially disrupt genetic networks, the co-expression networks were highly conserved across environments. Genes with higher network connectivity were under stronger stabilizing selection, suggesting that stabilizing selection on expression plays an important role in promoting network robustness.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Wen Huang ◽  
Mary Anna Carbone ◽  
Richard F. Lyman ◽  
Robert R. H. Anholt ◽  
Trudy F. C. Mackay

Abstract The genetics of phenotypic responses to changing environments remains elusive. Using whole-genome quantitative gene expression as a model, here we study how the genetic architecture of regulatory variation in gene expression changed in a population of fully sequenced inbred Drosophila melanogaster strains when flies developed in different environments (25 °C and 18 °C). We find a substantial fraction of the transcriptome exhibited genotype by environment interaction, implicating environmentally plastic genetic architecture of gene expression. Genetic variance in expression increases at 18 °C relative to 25 °C for most genes that have a change in genetic variance. Although the majority of expression quantitative trait loci (eQTLs) for the gene expression traits in the two environments are shared and have similar effects, analysis of the environment-specific eQTLs reveals enrichment of binding sites for two transcription factors. Finally, although genotype by environment interaction in gene expression could potentially disrupt genetic networks, the co-expression networks are highly conserved across environments. Genes with higher network connectivity are under stronger stabilizing selection, suggesting that stabilizing selection on expression plays an important role in promoting network robustness.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5782 ◽  
Author(s):  
Cynthia Dick ◽  
David N. Reznick ◽  
Cheryl Y. Hayashi

Sex-biased gene expression provides a means to achieve sexual dimorphism across a genome largely shared by both sexes. Trinidadian guppies are ideal to examine questions of sex-bias as they exhibit sexual dimorphism in ornamental coloration with male only expression. Here we use RNA-sequencing to quantify whole transcriptome gene expression differences, with a focus on differential expression of color genes between the sexes. We determine whether males express genes positively correlated with coloration at higher levels than females. We find that all the differentially expressed color genes were more highly expressed by males. Males also expressed all known black melanin synthesis genes at higher levels than females, regardless of whether the gene was significantly differentially expressed in the analysis. These differences correlated with the visual color differences between sexes at the stage sampled, as all males had ornamental black coloration apparent. We propose that sexual dimorphism in ornamental coloration is caused by male-biased expression of color genes.


2020 ◽  
Author(s):  
C Prince ◽  
R. E Mitchell ◽  
T. G. Richardson

AbstractBackgroundDeveloping functional understanding into the causal molecular drivers of immunological disease is a critical challenge in genomic medicine. Here we systematically apply Mendelian randomization (MR), genetic colocalization, immune cell-type enrichment and phenome-wide association methods to investigate the effect of genetically predicted gene expression on 12 autoimmune and 4 cancer outcomes.ResultsUsing whole blood derived estimates for regulatory variants from the eQTLGen consortium (n=31,684) we constructed genetic risk scores (r2<0.1) for 10,104 genes. Applying the inverse-variance weighted Mendelian randomization method transcriptome-wide whilst accounting for linkage disequilibrium structure identified 773 unique genes with evidence of a genetically predicted effect on at least one disease outcome (P<4.81 × 10−5). We next undertook genetic colocalization to investigate whether these effects may be confined to specific cell-types using gene expression data derived from 18 types of immune cells. This highlighted many cell-type dependent effects, such as PRKCQ expression and asthma risk (posterior probability of association (PPA)=0.998), which was T-cell specific, as well as TPM3 expression and prostate cancer risk (PPA=0.821), which was restricted to monocytes. Phenome-wide analyses on 320 complex traits allowed us to explore the shared genetic architecture and prioritize key drivers of disease risk, such as CASP10 which provided evidence of an effect on 7 cancer-related outcomes. Similarly, these evaluations of pervasive pleiotropy may be valuable for evaluations of therapeutic targets to help identify potential adverse effects.ConclusionsOur atlas of results can be used to characterize known and novel loci in autoimmune disease and cancer susceptibility, both in terms of developing insight into cell-type dependent effects as well as dissecting shared genetic architecture and disease pathways. As exemplar, we have highlighted several key findings in this study, although similar evaluations can be conducted interactively at http://mrcieu.mrsoftware.org/immuno_MR/.


2019 ◽  
Author(s):  
Danielle K. Herrig ◽  
Kim L. Vertacnik ◽  
Anna R. Kohrs ◽  
Catherine R. Linnen

Though seemingly bizarre, the dramatic post-embryonic transformation that occurs during metamorphosis is one of the most widespread and successful developmental strategies on the planet. The adaptive decoupling hypothesis (ADH) proposes that metamorphosis is an adaptation for optimizing expression of traits across life stages that experience opposing selection pressures. Similarly, sex-biased expression of traits is thought to evolve in response to sexually antagonistic selection. Both hypotheses predict that traits will be genetically decoupled among developmental stages and sexes, but direct comparisons between stage-specific and sex-specific decoupling are rare. Additionally, tests of the ADH have been hampered by a lack of suitable traits for among-stage comparisons and by uncertainties regarding how much decoupling is to be expected. To fill these voids, we characterize transcriptome-wide patterns of gene-expression decoupling in the hypermetamorphic and sexually dimorphic insect, Neodiprion lecontei. This species has three ecologically and morphologically distinct larval stages separated by molts, as well as a complete metamorphic transition that produces dimorphic adult males and females. Consistent with the ADH, we observe that: (1) the decoupling of gene expression becomes more pronounced as the ecological demands of developmental stages become more dissimilar and (2) gene-expression traits that mediate changing ecological interactions show stronger and more variable decoupling than expression traits that are likely to experience more uniform selection. We also find that gene-expression decoupling is more pronounced among major life stages than between the sexes. Overall, our results demonstrate that patterns of gene-expression decoupling can be predicted based on gene function and organismal ecology.


Author(s):  
Chunyu Li ◽  
Tianmi Yang ◽  
Ruwei Ou ◽  
Huifang Shang

Epidemiological and clinical studies have suggested comorbidity between schizophrenia and several neurodegenerative disorders. However, little is known whether there exists shared genetic architecture. To explore their relationship from a genetic and transcriptomic perspective, we applied polygenic and linkage disequilibrium-informed methods to examine the genetic correlation between schizophrenia and amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Alzheimer’s disease and frontotemporal dementia. We further combined genome-wide association summary statistics with large-scale transcriptomic datasets, to identify putative shared genes and explore related pathological tissues. We identified positive and significant correlation between schizophrenia and ALS at genetic (correlation 0.22; 95% CI: 0.16–0.28; p = 4.00E-04) and transcriptomic (correlation 0.08; 95% CI: 0.04–0.11; p = 0.034) levels. We further demonstrated that schizophrenia- and ALS-inferred gene expression overlap significantly in four tissues including skin, small intestine, brain cortex and lung, and highlighted three genes, namely GLB1L3, ZNHIT3 and TMEM194A as potential mediators of the correlation between schizophrenia and ALS. Our findings revealed overlapped gene expression profiles in specific tissues between schizophrenia and ALS, and identified novel potential shared genes. These results provided a better understanding for the pleiotropy of schizophrenia, and paved way for future studies to further elucidate the molecular drivers of schizophrenia.


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