Expression reduction in mammalian X chromosome evolution refutes Ohno’s hypothesis of dosage compensation

Lin, Fangqin; Xing, Ke; Zhang, Jianzhi; He, Xionglei

doi:10.1073/pnas.1201816109

Cited by 108 publications

(197 citation statements)

References 38 publications

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“…We next looked specifically at the evolution of the putative DEC genes preferentially expressed in the breast. Following a previous study 19 , we calculated a breast biased index (BBI) for each of the B700 putative DEC genes by dividing its expression level in the breast by its median expression level in all 16 normal tissues, obtaining 73 genes with BBI42 (Supplementary Data 5). We clustered the expression profiles of these 73 genes based on the pairwise Euclidean distance of these tissues or cells.…”

Section: Resultsmentioning

confidence: 99%

The reverse evolution from multicellularity to unicellularity during carcinogenesis

et al. 2015

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Theoretical reasoning suggests that cancer may result from a knockdown of the genetic constraints that evolved for the maintenance of metazoan multicellularity. By characterizing the whole-life history of a xenograft tumour, here we show that metastasis is driven by positive selection for general loss-of-function mutations on multicellularity-related genes. Expression analyses reveal mainly downregulation of multicellularity-related genes and an evolving expression profile towards that of embryonic stem cells, the cell type resembling unicellular life in its capacity of unlimited clonal proliferation. Also, the emergence of metazoan multicellularity B600 Myr ago is accompanied by an elevated birth rate of cancer genes, and there are more loss-of-function tumour suppressors than activated oncogenes in a typical tumour. These data collectively suggest that cancer represents a loss-of-functiondriven reverse evolution back to the unicellular 'ground state'. This cancer evolution model may account for inter-/intratumoural genetic heterogeneity, could explain distant-organ metastases and hold implications for cancer therapy.

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Section: Resultsmentioning

confidence: 99%

The reverse evolution from multicellularity to unicellularity during carcinogenesis

et al. 2015

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“…If the X chromosome is upregulated, transcriptional output from the present-day X and its autosomal progenitor should be similar. These studies found transcription from the current eutherian (the mammalian clade that includes humans and other placental mammals) X chromosome to be significantly lower compared to its autosomal progenitor (Julien et al 2012;Lin et al 2012). However, X and autosomal progenitor expression levels were similar when analyses were limited to highly expressed genes and those encoding for proteins involved in large (more than seven subunits) complexes (Julien et al 2012;Lin et al 2012).…”

Section: Transcription Increases To Above Autosomal Levels When the Dmentioning

confidence: 90%

“…To test Ohno's hypothesis more directly, attempts have been made to define those genes present on the autosomal progenitor of the X chromosome using species from major mammalian and bird lineages (Julien et al 2012;Lin et al 2012). If the X chromosome is upregulated, transcriptional output from the present-day X and its autosomal progenitor should be similar.…”

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confidence: 99%

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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“…This has most likely resulted in a twofold up-regulation of dosage-sensitive X-Chromosomal gene expression in males (Nguyen and Disteche 2006;Deng et al 2011Deng et al , 2013Brockdorff and Turner 2015). In addition, changes in autosomal genes whose products act in conjunction with Xencoded proteins contributed to a re-establishment of balanced gene expression (Julien et al 2012;Lin et al 2012;Necsulea and Kaessmann 2014). It is thought that up-regulation of the dosagesensitive genes on the X forced the specific inactivation of one of the two X Chromosomes in females (X Chromosome inactivation [XCI]) (Lyon 1961).…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Genomes of Ellobius species provide insight into the evolutionary dynamics of mammalian sex chromosomes

et al. 2016

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The X and Y sex chromosomes of placental mammals show hallmarks of a tumultuous evolutionary past. The X Chromosome has a rich and conserved gene content, while the Y Chromosome has lost most of its genes. In the Transcaucasian mole vole Ellobius lutescens, the Y Chromosome including Sry has been lost, and both females and males have a 17,X diploid karyotype. Similarly, the closely related Ellobius talpinus, has a 54,XX karyotype in both females and males. Here, we report the sequencing and assembly of the E. lutescens and E. talpinus genomes. The results indicate that the loss of the Y Chromosome in E. lutescens and E. talpinus occurred in two independent events. Four functional homologs of mouse Y-Chromosomal genes were detected in both female and male E. lutescens, of which three were also detected in the E. talpinus genome. One of these is Eif2s3y, known as the only Y-derived gene that is crucial for successful male meiosis. Female and male E. lutescens can carry one and the same X Chromosome with a largely conserved gene content, including all genes known to function in X Chromosome inactivation. The availability of the genomes of these mole vole species provides unique models to study the dynamics of sex chromosome evolution.

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Expression reduction in mammalian X chromosome evolution refutes Ohno’s hypothesis of dosage compensation

Cited by 108 publications

References 38 publications

The reverse evolution from multicellularity to unicellularity during carcinogenesis

The reverse evolution from multicellularity to unicellularity during carcinogenesis

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

Genomes of Ellobius species provide insight into the evolutionary dynamics of mammalian sex chromosomes

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