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Fitness Landscape of the Fission Yeast Genome

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Fitness Landscape of the Fission Yeast Genome. / Grech, Leanne; Jeffares, Daniel; Sadee, Christoph Y.; Rodriguez-Lopez, Maria; Bitton, Danny A.; Hoti, Mimoza; Biagosch, Carolina; Aravani, Dimitra; Speekenbrink, Maarten; Illingworth, Christopher J.R.; Schiffer, Philipp H.; Pidoux, Alison L.; Tong, Pin; Tallada, Victor A.; Allshire, Robin; Levin, Henry L.; Bahler, Jurg.

In: Molecular Biology and Evolution, Vol. 36, No. 8, 01.08.2019, p. 1612-1623.

Research output: Contribution to journalArticlepeer-review

Harvard

Grech, L, Jeffares, D, Sadee, CY, Rodriguez-Lopez, M, Bitton, DA, Hoti, M, Biagosch, C, Aravani, D, Speekenbrink, M, Illingworth, CJR, Schiffer, PH, Pidoux, AL, Tong, P, Tallada, VA, Allshire, R, Levin, HL & Bahler, J 2019, 'Fitness Landscape of the Fission Yeast Genome', Molecular Biology and Evolution, vol. 36, no. 8, pp. 1612-1623. https://doi.org/10.1093/molbev/msz113

APA

Grech, L., Jeffares, D., Sadee, C. Y., Rodriguez-Lopez, M., Bitton, D. A., Hoti, M., Biagosch, C., Aravani, D., Speekenbrink, M., Illingworth, C. J. R., Schiffer, P. H., Pidoux, A. L., Tong, P., Tallada, V. A., Allshire, R., Levin, H. L., & Bahler, J. (2019). Fitness Landscape of the Fission Yeast Genome. Molecular Biology and Evolution, 36(8), 1612-1623. https://doi.org/10.1093/molbev/msz113

Vancouver

Grech L, Jeffares D, Sadee CY, Rodriguez-Lopez M, Bitton DA, Hoti M et al. Fitness Landscape of the Fission Yeast Genome. Molecular Biology and Evolution. 2019 Aug 1;36(8):1612-1623. https://doi.org/10.1093/molbev/msz113

Author

Grech, Leanne ; Jeffares, Daniel ; Sadee, Christoph Y. ; Rodriguez-Lopez, Maria ; Bitton, Danny A. ; Hoti, Mimoza ; Biagosch, Carolina ; Aravani, Dimitra ; Speekenbrink, Maarten ; Illingworth, Christopher J.R. ; Schiffer, Philipp H. ; Pidoux, Alison L. ; Tong, Pin ; Tallada, Victor A. ; Allshire, Robin ; Levin, Henry L. ; Bahler, Jurg. / Fitness Landscape of the Fission Yeast Genome. In: Molecular Biology and Evolution. 2019 ; Vol. 36, No. 8. pp. 1612-1623.

Bibtex - Download

@article{d33e43f75cf845b4bfd658d3ffaa5469,
title = "Fitness Landscape of the Fission Yeast Genome",
abstract = "The relationship between DNA sequence, biochemical function and molecular evolution is relatively well-described for protein-coding regions of genomes, but far less clear in non coding regions, particularly in eukaryote genomes. In part, this is because we lack a complete description of the essential non-coding elements in a eukaryote genome. To contribute to this challenge, we used saturating transposon mutagenesis to interrogate the Schizosaccharomyces pombe genome. We generated 31 million transposon insertions, a theoretical coverage of 2.4 insertions per genomic site. We applied a five-state hidden Markov model (HMM) to distinguish insertion-depleted regions from insertion biases. Both raw insertion-density and HMM-defined fitness estimates showed significant quantitative relationships to gene knockout fitness, genetic diversity, divergence and expected functional regions based on transcription and gene annotations. Through several analyses, we conclude that transposon insertions produced fitness effects in 66-90% of the genome, including substantial portions of the non-coding regions. Based on the HMM, we estimate that 10% of the insertion depleted sites in the genome showed no signal of conservation between species and were weakly transcribed, demonstrating limitations of comparative genomics and transcriptomics to detect functional units. In this species, 3{\textquoteright} and 5{\textquoteright} untranslated regions were the most prominent insertion-depleted regions that were not represented in measures of constraint from comparative genomics. We conclude that the combination of transposon mutagenesis, evolutionary and biochemical data can provide new insights into the relationship between genome function and molecular evolution.",
author = "Leanne Grech and Daniel Jeffares and Sadee, {Christoph Y.} and Maria Rodriguez-Lopez and Bitton, {Danny A.} and Mimoza Hoti and Carolina Biagosch and Dimitra Aravani and Maarten Speekenbrink and Illingworth, {Christopher J.R.} and Schiffer, {Philipp H.} and Pidoux, {Alison L.} and Pin Tong and Tallada, {Victor A.} and Robin Allshire and Levin, {Henry L.} and Jurg Bahler",
note = "{\textcopyright} The Author(s) 2019. ",
year = "2019",
month = aug,
day = "1",
doi = "10.1093/molbev/msz113",
language = "English",
volume = "36",
pages = "1612--1623",
journal = "Molecular Biology and Evolution",
issn = "0737-4038",
publisher = "Oxford University Press",
number = "8",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Fitness Landscape of the Fission Yeast Genome

AU - Grech, Leanne

AU - Jeffares, Daniel

AU - Sadee, Christoph Y.

AU - Rodriguez-Lopez, Maria

AU - Bitton, Danny A.

AU - Hoti, Mimoza

AU - Biagosch, Carolina

AU - Aravani, Dimitra

AU - Speekenbrink, Maarten

AU - Illingworth, Christopher J.R.

AU - Schiffer, Philipp H.

AU - Pidoux, Alison L.

AU - Tong, Pin

AU - Tallada, Victor A.

AU - Allshire, Robin

AU - Levin, Henry L.

AU - Bahler, Jurg

N1 - © The Author(s) 2019.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - The relationship between DNA sequence, biochemical function and molecular evolution is relatively well-described for protein-coding regions of genomes, but far less clear in non coding regions, particularly in eukaryote genomes. In part, this is because we lack a complete description of the essential non-coding elements in a eukaryote genome. To contribute to this challenge, we used saturating transposon mutagenesis to interrogate the Schizosaccharomyces pombe genome. We generated 31 million transposon insertions, a theoretical coverage of 2.4 insertions per genomic site. We applied a five-state hidden Markov model (HMM) to distinguish insertion-depleted regions from insertion biases. Both raw insertion-density and HMM-defined fitness estimates showed significant quantitative relationships to gene knockout fitness, genetic diversity, divergence and expected functional regions based on transcription and gene annotations. Through several analyses, we conclude that transposon insertions produced fitness effects in 66-90% of the genome, including substantial portions of the non-coding regions. Based on the HMM, we estimate that 10% of the insertion depleted sites in the genome showed no signal of conservation between species and were weakly transcribed, demonstrating limitations of comparative genomics and transcriptomics to detect functional units. In this species, 3’ and 5’ untranslated regions were the most prominent insertion-depleted regions that were not represented in measures of constraint from comparative genomics. We conclude that the combination of transposon mutagenesis, evolutionary and biochemical data can provide new insights into the relationship between genome function and molecular evolution.

AB - The relationship between DNA sequence, biochemical function and molecular evolution is relatively well-described for protein-coding regions of genomes, but far less clear in non coding regions, particularly in eukaryote genomes. In part, this is because we lack a complete description of the essential non-coding elements in a eukaryote genome. To contribute to this challenge, we used saturating transposon mutagenesis to interrogate the Schizosaccharomyces pombe genome. We generated 31 million transposon insertions, a theoretical coverage of 2.4 insertions per genomic site. We applied a five-state hidden Markov model (HMM) to distinguish insertion-depleted regions from insertion biases. Both raw insertion-density and HMM-defined fitness estimates showed significant quantitative relationships to gene knockout fitness, genetic diversity, divergence and expected functional regions based on transcription and gene annotations. Through several analyses, we conclude that transposon insertions produced fitness effects in 66-90% of the genome, including substantial portions of the non-coding regions. Based on the HMM, we estimate that 10% of the insertion depleted sites in the genome showed no signal of conservation between species and were weakly transcribed, demonstrating limitations of comparative genomics and transcriptomics to detect functional units. In this species, 3’ and 5’ untranslated regions were the most prominent insertion-depleted regions that were not represented in measures of constraint from comparative genomics. We conclude that the combination of transposon mutagenesis, evolutionary and biochemical data can provide new insights into the relationship between genome function and molecular evolution.

U2 - 10.1093/molbev/msz113

DO - 10.1093/molbev/msz113

M3 - Article

C2 - 31077324

VL - 36

SP - 1612

EP - 1623

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 8

ER -