Transcriptional and mutational signatures of the Drosophila ageing germline.
Transcriptional and mutational signatures of the Drosophila ageing germline.
复制标题
DOI：
10.1038/s41559-022-01958-x
复制
发表时间：
2023-03
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
作者：
衰老是一个复杂的生物学过程，伴随着基因表达和突变负荷的变化。在包括人类在内的许多物种中，年长的父亲会传递更多来自父亲的新生突变;然而，驱动这种模式的细胞基础和细胞类型仍不清楚。为了探索这种现象的根本原因，我们对年轻和年老雄性果蝇的睾丸进行了单细胞RNA测序（scRNA-seq），并对同一果蝇的体细胞组织进行了基因组测序（DNA-seq）。我们发现，从老年和年轻的苍蝇的早期生殖细胞进入精子发生相似的突变负荷，但老年苍蝇是不太能够在精子发生过程中删除突变。在精子发生过程中，老细胞中的突变也可能增加。我们的数据显示，老年和年轻的苍蝇有不同的突变偏好。许多种类的基因显示出在较老的果蝇的生殖系中增加的减数分裂后表达。晚期精子发生偏向基因的dN/dS比早期精子发生偏向基因的高，支持晚期精子发生是进化创新的来源这一假设。令人惊讶的是，偏向年轻生殖细胞的基因比偏向老年生殖细胞的基因显示出更高的dN/dS。我们的研究结果提供了新的见解生殖细胞在从头突变的作用。
Aging is a complex biological process that is accompanied by changes in gene expression and mutational load. In many species, including humans, older fathers pass on more paternally-derived de novo mutations; however, the cellular basis and cell types driving this pattern are still unclear. To explore the root causes of this phenomenon, we performed single-cell RNA-sequencing (scRNA-seq) on testes from young and old male Drosophila, as well as genomic sequencing (DNA-seq) on somatic tissues from the same flies. We found that early germ cells from old and young flies enter spermatogenesis with similar mutational loads, but older flies are less able to remove mutations during spermatogenesis. Mutations in old cells may also increase during spermatogenesis. Our data reveal that old and young flies have distinct mutational biases. Many classes of genes show increased post-meiotic expression in the germlines of older flies. Late spermatogenesis-biased genes have higher dN/dS than early spermatogenesis-biased genes, supporting the hypothesis that late spermatogenesis is a source of evolutionary innovation. Surprisingly, genes biased in young germ cells show higher dN/dS than genes biased in old germ cells. Our results provide novel insights into the role of the germline in de novo mutation.
登录
查看更多内容
影响因子：
4.1
作者：
Li, WH;Ellsworth, DL;HewettEmmett, D
通讯作者：
HewettEmmett, D
DOI：
10.1073/pnas.1100233108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Gao, Jian-Jun;Pan, Xue-Rong;Fu, Yun-Xin
通讯作者：
Fu, Yun-Xin
影响因子：
4.5
作者：
Juge, Francois;Fernando, Celine;Tazi, Jamal
通讯作者：
Tazi, Jamal
影响因子：
25
作者：
Li, Wanhe;Prazak, Lisa;Chatterjee, Nabanita;Grueninger, Servan;Krug, Lisa;Theodorou, Delphine;Dubnau, Josh
通讯作者：
Dubnau, Josh
DOI：
10.1073/pnas.1901259116
发表时间：
2019-05-07
影响因子：
11.1
作者：
Gao, Ziyue;Moorjani, Priya;Przeworski, Molly
通讯作者：
Przeworski, Molly