Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity

Yu H. Sun; Hongxiao Cui; Chi Song; Jiafei Teng Shen; Xiaoyu Zhuo; Ruoqiao Huiyi Wang; Xiaohui Yu; Rudo Ndamba; Qian Mu; Hanwen Gu; Duolin Wang; Gayathri Guru Murthy; Pidong Li; Fan Liang; Lei Liu; Qing Tao; Ying Wang; Sara Orlowski; Qi Xu; Huaijun Zhou; Jarra Jagne; Omer Gokcumen; Nick Anthony; Xin Zhao; Xin Zhiguo Li

doi:10.1038/s41467-023-36354-x

Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity

Yu H. Sun, Hongxiao Cui, Chi Song, Jiafei Teng Shen, Xiaoyu Zhuo, Ruoqiao Huiyi Wang, Xiaohui Yu, Rudo Ndamba, Qian Mu, Hanwen Gu, Duolin Wang, Gayathri Guru Murthy, Pidong Li, Fan Liang, Lei Liu, Qing Tao, Ying Wang, Sara Orlowski, Qi Xu, Huaijun ZhouJarra Jagne, Omer Gokcumen, Nick Anthony, Xin Zhao, Xin Zhiguo Li

Department of Genetics

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences.

Original language	English
Article number	812
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-36354-x
State	Published - Dec 2023

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Sun, Y. H., Cui, H., Song, C., Shen, J. T., Zhuo, X., Wang, R. H., Yu, X., Ndamba, R., Mu, Q., Gu, H., Wang, D., Murthy, G. G., Li, P., Liang, F., Liu, L., Tao, Q., Wang, Y., Orlowski, S., Xu, Q., ... Li, X. Z. (2023). Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity. Nature communications, 14(1), Article 812. https://doi.org/10.1038/s41467-023-36354-x

@article{54d86694f6d749ddb06d5ab95190edb8,

title = "Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity",

abstract = "Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences.",

author = "Sun, {Yu H.} and Hongxiao Cui and Chi Song and Shen, {Jiafei Teng} and Xiaoyu Zhuo and Wang, {Ruoqiao Huiyi} and Xiaohui Yu and Rudo Ndamba and Qian Mu and Hanwen Gu and Duolin Wang and Murthy, {Gayathri Guru} and Pidong Li and Fan Liang and Lei Liu and Qing Tao and Ying Wang and Sara Orlowski and Qi Xu and Huaijun Zhou and Jarra Jagne and Omer Gokcumen and Nick Anthony and Xin Zhao and Li, {Xin Zhiguo}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-36354-x",

language = "English",

volume = "14",

journal = "Nature communications",

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Sun, YH, Cui, H, Song, C, Shen, JT, Zhuo, X, Wang, RH, Yu, X, Ndamba, R, Mu, Q, Gu, H, Wang, D, Murthy, GG, Li, P, Liang, F, Liu, L, Tao, Q, Wang, Y, Orlowski, S, Xu, Q, Zhou, H, Jagne, J, Gokcumen, O, Anthony, N, Zhao, X & Li, XZ 2023, 'Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity', Nature communications, vol. 14, no. 1, 812. https://doi.org/10.1038/s41467-023-36354-x

TY - JOUR

T1 - Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity

AU - Sun, Yu H.

AU - Cui, Hongxiao

AU - Song, Chi

AU - Shen, Jiafei Teng

AU - Zhuo, Xiaoyu

AU - Wang, Ruoqiao Huiyi

AU - Yu, Xiaohui

AU - Ndamba, Rudo

AU - Mu, Qian

AU - Gu, Hanwen

AU - Wang, Duolin

AU - Murthy, Gayathri Guru

AU - Li, Pidong

AU - Liang, Fan

AU - Liu, Lei

AU - Tao, Qing

AU - Wang, Ying

AU - Orlowski, Sara

AU - Xu, Qi

AU - Zhou, Huaijun

AU - Jagne, Jarra

AU - Gokcumen, Omer

AU - Anthony, Nick

AU - Zhao, Xin

AU - Li, Xin Zhiguo

PY - 2023/12

Y1 - 2023/12

N2 - Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences.

AB - Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences.

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U2 - 10.1038/s41467-023-36354-x

DO - 10.1038/s41467-023-36354-x

M3 - Article

C2 - 36781861

AN - SCOPUS:85147975833

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 812

ER -

Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity

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