Haploinsufficiency and the sex chromosomes from yeasts to humans

Clare, Michaela de; Pir, Pınar; Oliver, Stephen G.

doi:10.1186/1741-7007-9-15

Cited by 28 publications

(25 citation statements)

References 44 publications

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“…Haplo-insufficient genes have been well characterized in Saccharomyces cerevisae and can be used to predict haplo-insufficiency in other metazoan species (de Clare et al 2011). Orthologs of yeast haplo-insufficient genes are excluded from the X chromosome in humans and C. elegans (de Clare et al 2011). Here, we found that this trend holds for the four other nematode species ( Figure 8B).…”

Section: Effect Of X Localization On Gene Expressionsupporting

confidence: 64%

“…A reduction in their gene copy number from two to one results in a significant reduction of overall fitness. Haplo-insufficient genes have been well characterized in Saccharomyces cerevisae and can be used to predict haplo-insufficiency in other metazoan species (de Clare et al 2011). Orthologs of yeast haplo-insufficient genes are excluded from the X chromosome in humans and C. elegans (de Clare et al 2011).…”

Section: Effect Of X Localization On Gene Expressionmentioning

confidence: 99%

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Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

et al. 2014

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Studies of X chromosome evolution in various organisms have indicated that sex-biased genes are nonrandomly distributed between the X and autosomes. Here, to extend these studies to nematodes, we annotated and analyzed X chromosome gene content in four Caenorhabditis species and in Pristionchus pacificus. Our gene expression analyses comparing young adult male and female mRNAseq data indicate that, in general, nematode X chromosomes are enriched for genes with high female-biased expression and depleted of genes with high male-biased expression. Genes with low sex-biased expression do not show the same trend of X chromosome enrichment and depletion. Combined with the observation that highly sex-biased genes are primarily expressed in the gonad, differential distribution of sex-biased genes reflects differences in evolutionary pressures linked to tissue-specific regulation of X chromosome transcription. Our data also indicate that X dosage imbalance between males (XO) and females (XX) is influential in shaping both expression and gene content of the X chromosome. Predicted upregulation of the single male X to match autosomal transcription (Ohno's hypothesis) is supported by our observation that overall transcript levels from the X and autosomes are similar for highly expressed genes. However, comparison of differentially located one-to-one orthologs between C. elegans and P. pacificus indicates lower expression of X-linked orthologs, arguing against X upregulation. These contradicting observations may be reconciled if X upregulation is not a global mechanism but instead acts locally on a subset of tissues and X-linked genes that are dosage sensitive. IN an XY sex-determination system, male and female genomes are identical with the exception of the male-specific Y chromosome, which bears few genes (Charlesworth et al. 2005). This is particularly true when the Y chromosome is thought to be completely lost, as is the case for C. elegans and many other nematodes (Walton 1940). Because gene content is the same, phenotypic differences between males and females, termed "sexual dimorphisms," must be caused by differential gene expression between the two sexes (Connallon and Knowles 2005;Ellegren and Parsch 2007). Throughout the article, such differentially expressed genes are referred to as "sex biased." As males and females have different fitness optima, a trait that is beneficial to one sex can be harmful to the other (termed sexual antagonism) (Rice and Chippindale 2001;Arnqvist 2004;Connallon and Knowles 2005;Ellegren and Parsch 2007;Mank et al. 2008a;Rice 1984). The evolution of sex-biased gene expression is thought to mediate the effects of sexual antagonism and allow for achievement of sex-specific fitness. Previous studies have indicated that anywhere between 30 and 60% of metazoan genes may be sex biased Parisi et al. 2004;Reinke et al. 2004;Yang et al. 2006;Reinius et al. 2008;Small et al. 2009;Innocenti and Morrow 2010;Assis et al. 2012;Reinius et al. 2012;Thomas et al. 2012). Genes with sex-biased exp...

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Section: Effect Of X Localization On Gene Expressionsupporting

confidence: 64%

Section: Effect Of X Localization On Gene Expressionmentioning

confidence: 99%

Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

et al. 2014

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“…Sex chromosomes are subject to unique evolutionary processes and mechanisms (5,(45)(46)(47). Our observations about the yeast MAT chromosome are reminiscent of the movement of genes out of the mammalian X chromosome (48,49), but unlike that process we do not suggest that the "out-of-MAT" gene movements are driven by natural selection.…”

Section: Discussionmentioning

confidence: 63%

Evolutionary erosion of yeast sex chromosomes by mating-type switching accidents

Gordon

Armisén

Proux‐Wéra

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

136

180

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We investigate yeast sex chromosome evolution by comparing genome sequences from 16 species in the family Saccharomycetaceae, including data from genera Tetrapisispora, Kazachstania, Naumovozyma, and Torulaspora. We show that although most yeast species contain a mating-type (MAT) locus and silent HML and HMR loci structurally analogous to those of Saccharomyces cerevisiae, their detailed organization is highly variable and indicates that the MAT locus is a deletion hotspot. Over evolutionary time, chromosomal genes located immediately beside MAT have continually been deleted, truncated, or transposed to other places in the genome in a process that is gradually shortening the distance between MAT and HML. Each time a gene beside MAT is removed by deletion or transposition, the next gene on the chromosome is brought into proximity with MAT and is in turn put at risk for removal. This process has also continually replaced the triplicated sequence regions, called Z and X, that allow HML and HMR to be used as templates for DNA repair at MAT during mating-type switching. We propose that the deletion and transposition events are caused by evolutionary accidents during matingtype switching, combined with natural selection to keep MAT and HML on the same chromosome. The rate of deletion accelerated greatly after whole-genome duplication, probably because genes were redundant and could be deleted without requiring transposition. We suggest that, despite its mutational cost, switching confers an evolutionary benefit by providing a way for an isolated germinating spore to reform spores if the environment is too poor.

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“…However, their results are not comparable with ours because they examined yeast growth in a medium containing glucose (YPD) that represses RC genes, while we performed our experiments in YPG, which forces the cells to rely on mitochondrial respiration and therefore stimulates the expression of RC genes. Another study showed that in yeast haploinsufficient genes are overrepresented in chromosome III,14 but COQ4 maps to S cerevisiae chromosome IV.…”

Section: Discussionmentioning

confidence: 99%

Haploinsufficiency ofCOQ4causes coenzyme Q₁₀deficiency

et al. 2012

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Background COQ4 encodes a protein that organises the multienzyme complex for the synthesis of coenzyme Q10 (CoQ10). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ10 deficiency. Methods A complete molecular and biochemical characterisation of the patient’s fibroblasts and of a yeast model were performed. Results The study found reduced COQ4 expression (48% of controls), CoQ10 content and biosynthetic rate (44% and 43% of controls), and activities of respiratory chain complex II+III. Cells displayed a growth defect that was corrected by the addition of CoQ10 to the culture medium. Knockdown of COQ4 in HeLa cells also resulted in a reduction of CoQ10. Diploid yeast haploinsufficient for COQ4 displayed similar CoQ deficiency. Haploinsufficency of other genes involved in CoQ10 biosynthesis does not cause CoQ deficiency, underscoring the critical role of COQ4. Oral CoQ10 supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued. Conclusion Mutations of COQ4 should be searched for in patients with CoQ10 deficiency and encephalomyopathy; patients with genomic rearrangements involving COQ4 should be screened for CoQ10 deficiency, as they could benefit from supplementation.

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Haploinsufficiency and the sex chromosomes from yeasts to humans

Cited by 28 publications

References 44 publications

Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

Evolutionary erosion of yeast sex chromosomes by mating-type switching accidents

Haploinsufficiency ofCOQ4causes coenzyme Q₁₀deficiency

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Haploinsufficiency and the sex chromosomes from yeasts to humans

Cited by 28 publications

References 44 publications

Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

Evolutionary erosion of yeast sex chromosomes by mating-type switching accidents

Haploinsufficiency ofCOQ4causes coenzyme Q10deficiency

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Haploinsufficiency ofCOQ4causes coenzyme Q₁₀deficiency