TY - JOUR
T1 - Evolution of yin and yang isoforms of a chromatin remodeling subunit precedes the creation of two genes
AU - Xu, Wen
AU - Long, Lijiang
AU - Zhao, Yuehui
AU - Stevens, Lewis
AU - Felipe, Irene
AU - Munoz, Javier
AU - Ellis, Ronald E.
AU - McGrath, Patrick T.
N1 - Funding Information:
We thank the Caenorhabditis Genetics Center, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440), for strains, and WormBase for information. We are grateful to Rachael Workman and Winston Timp for sharing Oxford Nanopore reads of nurf-1 prior to publication. We thank Matthew Rockman, Luke Noble, Janna Fierst, Erich Schwarz, and Janet Young for access to unpublished genomic data. We thank F.X Real for support, valuable discussions, and comments on the manuscript and G Roncador and the CNIO Monoclonal Antibody Core Unit for helpful contributions. We also thank Todd Streelman, Greg Gibson, Soojin Yi, David Katz, Annalise Paaby, and members of the McGrath lab for discussions, and Annalise Paaby and Erik Andersen for comments on the manuscript. This work was supported by NIH R01GM114170 (to PTM), R01GM121688 (to R E E), and a CNIO friends/Juegaterapia grant (to IF). Work at CNIO was supported, in part, by grant RTI2018-101071-B-I00 from Ministerio de Ciencia, Innovación y Universidades. CNIO is supported by Ministerio de Ciencia, Innovación y Universidades as a Centro de Excelencia Severo Ochoa SEV-2015–0510.
Funding Information:
We thank the Caenorhabditis Genetics Center, which is funded by NIH Office of Research Infrastruc- ture Programs (P40 OD010440), for strains, and WormBase for information. We are grateful to Rachael Workman and Winston Timp for sharing Oxford Nanopore reads of nurf-1 prior to publication. We thank Matthew Rockman, Luke Noble, Janna Fierst, Erich Schwarz, and Janet Young for access to unpublished genomic data. We thank F.X Real for support, valuable discussions, and com- ments on the manuscript and G Roncador and the CNIO Monoclonal Antibody Core Unit for helpful contributions. We also thank Todd Streelman, Greg Gibson, Soojin Yi, David Katz, Annalise Paaby, and members of the McGrath lab for discussions, and Annalise Paaby and Erik Andersen for comments on the manuscript. This work was supported by NIH R01GM114170 (to PTM), R01GM121688 (to R E E), and a CNIO friends/Juegaterapia grant (to IF). Work at CNIO was supported, in part, by grant RTI2018-101071-B-I00 from Ministerio de Ciencia, Innovacio?n y Universidades. CNIO is supported by Ministerio de Ciencia, Innovacio? n y Universidades as a Centro de Excelencia Severo Ochoa SEV-2015?0510.
Publisher Copyright:
© Xu et al.
PY - 2019/9
Y1 - 2019/9
N2 - Genes can encode multiple isoforms, broadening their functions and providing a molecular substrate to evolve phenotypic diversity. Evolution of isoform function is a potential route to adapt to new environments. Here we show that de novo, beneficial alleles in the nurf-1 gene became fixed in two laboratory lineages of C. elegans after isolation from the wild in 1951, before methods of cryopreservation were developed. nurf-1 encodes an ortholog of BPTF, a large (>300 kD) multidomain subunit of the NURF chromatin remodeling complex. Using CRISPR-Cas9 genome editing and transgenic rescue, we demonstrate that in C. elegans, nurf-1 has split into two, largely non-overlapping isoforms (NURF-1.D and NURF-1.B, which we call Yin and Yang, respectively) that share only two of 26 exons. Both isoforms are essential for normal gametogenesis but have opposite effects on male/female gamete differentiation. Reproduction in hermaphrodites, which involves production of both sperm and oocytes, requires a balance of these opposing Yin and Yang isoforms. Transgenic rescue and genetic position of the fixed mutations suggest that different isoforms are modified in each laboratory strain. In a related clade of Caenorhabditis nematodes, the shared exons have duplicated, resulting in the split of the Yin and Yang isoforms into separate genes, each containing approximately 200 amino acids of duplicated sequence that has undergone accelerated protein evolution following the duplication. Associated with this duplication event is the loss of two additional nurf-1 transcripts, including the long-form transcript and a newly identified, highly expressed transcript encoded by the duplicated exons. We propose these lost transcripts are non-functional side products necessary to transcribe the Yin and Yang transcripts in the same cells. Our work demonstrates how gene sharing, through the production of multiple isoforms, can precede the creation of new, independent genes.
AB - Genes can encode multiple isoforms, broadening their functions and providing a molecular substrate to evolve phenotypic diversity. Evolution of isoform function is a potential route to adapt to new environments. Here we show that de novo, beneficial alleles in the nurf-1 gene became fixed in two laboratory lineages of C. elegans after isolation from the wild in 1951, before methods of cryopreservation were developed. nurf-1 encodes an ortholog of BPTF, a large (>300 kD) multidomain subunit of the NURF chromatin remodeling complex. Using CRISPR-Cas9 genome editing and transgenic rescue, we demonstrate that in C. elegans, nurf-1 has split into two, largely non-overlapping isoforms (NURF-1.D and NURF-1.B, which we call Yin and Yang, respectively) that share only two of 26 exons. Both isoforms are essential for normal gametogenesis but have opposite effects on male/female gamete differentiation. Reproduction in hermaphrodites, which involves production of both sperm and oocytes, requires a balance of these opposing Yin and Yang isoforms. Transgenic rescue and genetic position of the fixed mutations suggest that different isoforms are modified in each laboratory strain. In a related clade of Caenorhabditis nematodes, the shared exons have duplicated, resulting in the split of the Yin and Yang isoforms into separate genes, each containing approximately 200 amino acids of duplicated sequence that has undergone accelerated protein evolution following the duplication. Associated with this duplication event is the loss of two additional nurf-1 transcripts, including the long-form transcript and a newly identified, highly expressed transcript encoded by the duplicated exons. We propose these lost transcripts are non-functional side products necessary to transcribe the Yin and Yang transcripts in the same cells. Our work demonstrates how gene sharing, through the production of multiple isoforms, can precede the creation of new, independent genes.
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U2 - 10.7554/eLife.48119
DO - 10.7554/eLife.48119
M3 - Article
C2 - 31498079
AN - SCOPUS:85072508500
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e48119
ER -