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Sex differences in carbohydrate metabolism are linked to gene expression in Caenorhabditis elegans.

ABSTRACT: The male and the hermaphrodite forms of the nematode Caenorhabditis elegans (C. elegans) differ markedly in anatomy, nervous system and behavior at adulthood. Using the male mutants fog-2, him-5, and him-8, we compared body proportions and composition, and aspects of carbohydrate metabolism and gene expression between the C. elegans sexes in three adult stages. In all experiments, both sexes were grown on the same plate and separated using flow cytometry. The fat to fat-free mass ratio and the body volume-adjusted fat mass is similar between the sexes, although the body size is more than 50% smaller in adult males than in age-matched hermaphrodites. The volume-adjusted total RNA content is approximately 2-fold lower in males. Biochemical and NMR-based analyses reveal higher trehalose levels and much lower glucose levels in males than in hermaphrodites. The resulting trehalose-to-glucose ratio is 5.4-fold higher in males. These sex differences are reflected in gene expression data because the genes encoding key enzymes of the glycolysis and trehalose synthesis pathways are more highly expressed in males than in hermaphrodites. Notably, expression of the phosphofructokinase gene (C50F4.2) is 29-fold higher in males. Comparative analysis of gene expression data identifies 285 male-specific and 160 hermaphrodite-specific genes. These include transcription factor and C-type lectin-encoding genes. More than 35% of all C-type lectin genes are more highly expressed in males. The expression of many C-type lectin genes differs by a factor of >100 between the sexes. In conclusion, we found sex differences in carbohydrate metabolism that are linked to gene expression and identified certain lectin genes that are differentially expressed by the C. elegans sexes.

SUBMITTER: Miersch C

PROVIDER: S-EPMC3439400 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Sex differences in carbohydrate metabolism are linked to gene expression in Caenorhabditis elegans.

Miersch Claudia C Döring Frank F

PloS one 20120911 9

The male and the hermaphrodite forms of the nematode Caenorhabditis elegans (C. elegans) differ markedly in anatomy, nervous system and behavior at adulthood. Using the male mutants fog-2, him-5, and him-8, we compared body proportions and composition, and aspects of carbohydrate metabolism and gene expression between the C. elegans sexes in three adult stages. In all experiments, both sexes were grown on the same plate and separated using flow cytometry. The fat to fat-free mass ratio and the b ...[more]

PMID: 22984551

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Project description:Understanding sex differences in colon cancer is essential to advance disease prevention, diagnosis, and treatment. Males have a higher risk of developing colon cancer and a lower survival rate than women. However, the molecular features that drive these sex differences are poorly understood. In this study, we use both transcript-based and gene regulatory network methods to analyze RNA-seq data from The Cancer Genome Atlas for 445 patients with colon cancer. We compared gene expression between tumors in men and women and observed significant sex differences in sex chromosome genes only. We then inferred patient-specific gene regulatory networks and found significant regulatory differences between males and females, with drug and xenobiotics metabolism via cytochrome P450 pathways more strongly targeted in females. This finding was validated in a dataset of 1,193 patients from five independent studies. While targeting, the drug metabolism pathway did not change overall survival for males treated with adjuvant chemotherapy, females with greater targeting showed an increase in 10-year overall survival probability, 89% [95% confidence interval (CI), 78-100] survival compared with 61% (95% CI, 45-82) for women with lower targeting, respectively (P = 0.034). Our network analysis uncovers patterns of transcriptional regulation that differentiate male and female colon cancer and identifies differences in regulatory processes involving the drug metabolism pathway associated with survival in women who receive adjuvant chemotherapy. This approach can be used to investigate the molecular features that drive sex differences in other cancers and complex diseases.Significance: A network-based approach reveals that sex-specific patterns of gene targeting by transcriptional regulators are associated with survival outcome in colon cancer. This approach can be used to understand how sex influences progression and response to therapies in other cancers. Cancer Res; 78(19); 5538-47. ©2018 AACR.

Dataset Information

Sex differences in carbohydrate metabolism are linked to gene expression in Caenorhabditis elegans.

Publications

Sex differences in carbohydrate metabolism are linked to gene expression in Caenorhabditis elegans.

Similar Datasets

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