转座元件的表达与人类性染色体数量相关。

Transposable element expression is associated with sex chromosome number in humans.

作者信息

Teoli Jordan, Merenciano Miriam, Fablet Marie, Necsulea Anamaria, Siqueira-de-Oliveira Daniel, Brandulas-Cammarata Alessandro, Labalme Audrey, Lejeune Hervé, Lemaitre Jean-François, Gueyffier François, Sanlaville Damien, Bardel Claire, Vieira Cristina, Marais Gabriel Ab, Plotton Ingrid

机构信息

Laboratoire de Biochimie et Biologie Moléculaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Bron, France.

Laboratoire de Biométrie et Biologie Evolutive, UMR 5558, CNRS, Universite Claude Bernard Lyon 1, Villeurbanne, France.

出版信息

PLoS Genet. 2025 Jun 26;21(6):e1011668. doi: 10.1371/journal.pgen.1011668. eCollection 2025 Jun.

Abstract

Why women live longer than men is still an open question in human biology. Sex chromosomes have been proposed to play a role in the observed sex gap in longevity, and the Y male chromosome has been suspected of having a potential toxic genomic impact on male longevity. It has been hypothesized that transposable element (TE) repression declines with age, potentially leading to detrimental effects such as somatic mutations and disrupted gene expression, which may accelerate the aging process. Given that the Y chromosome is rich in repeats, age-related increases in TE expression could be more pronounced in males, likely contributing to their reduced longevity compared to females. In this work, we first studied whether TE expression is associated with the number of sex chromosomes in humans. We analyzed blood transcriptomic data obtained from individuals of different karyotype compositions: 46,XX females (normal female karyotype), 46,XY males (normal male karyotype), as well as males with abnormal karyotypes, such as 47,XXY, and 47,XYY. We found that sex chromosomes might be associated to TE expression, with the presence and number of Y chromosomes particularly associated with a global increase in TE expression. This tendency was also observed across several TE subfamilies. We also tested whether TE expression is higher in older males than in older females using published human blood transcriptomic data from the Genotype-Tissue Expression (GTEx) project. However, we did not find increased TE expression in older males compared to older females probably due to the heterogeneity of the dataset. Our findings suggest an association between sex chromosome content and TE expression and open a new window to study the toxic effect of the Y chromosome in human longevity.

摘要

女性为何比男性寿命长仍是人类生物学中一个悬而未决的问题。性染色体被认为在观察到的寿命性别差异中发挥作用,而Y男性染色体被怀疑对男性寿命具有潜在的基因组毒性影响。据推测,转座元件(TE)抑制作用会随着年龄增长而下降,这可能会导致诸如体细胞突变和基因表达紊乱等有害影响,进而加速衰老过程。鉴于Y染色体富含重复序列,与年龄相关的TE表达增加在男性中可能更为明显,这可能是导致男性寿命比女性短的原因之一。在这项研究中,我们首先研究了TE表达是否与人类性染色体数量有关。我们分析了从不同核型组成的个体获得的血液转录组数据:46,XX女性(正常女性核型)、46,XY男性(正常男性核型),以及核型异常的男性,如47,XXY和47,XYY。我们发现性染色体可能与TE表达有关,Y染色体的存在和数量尤其与TE表达的整体增加有关。在几个TE亚家族中也观察到了这种趋势。我们还使用来自基因型-组织表达(GTEx)项目已发表的人类血液转录组数据,测试了老年男性的TE表达是否高于老年女性。然而,由于数据集的异质性,我们没有发现老年男性的TE表达比老年女性增加。我们的研究结果表明性染色体含量与TE表达之间存在关联,并为研究Y染色体在人类寿命中的毒性作用打开了一扇新窗口。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/484b/12225981/bb2d038b91f6/pgen.1011668.g001.jpg

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