Abstract
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.
Highlights
There is general interest in understanding how animals adapt to new environments
Here we show that de novo, beneficial alleles in the nurf-1 gene fixed in two laboratory strains 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 (>300kD) multidomain subunit of the nucleosome remodeling factor (NURF) chromatin remodeling complex
To understand why nurf-1 might be targeted, we explored the in vivo role in C. elegans development by taking advantage of CRISPR-Cas9 to test causal relationships that inform laboratory evolution and fitness effects
Summary
There is general interest in understanding how animals adapt to new environments. What are the alleles that matter to positive selection and what sort of genes do they target? Since methods were developed to map and identify the genes harboring causative genetic variation, researchers have often isolated changes in the same gene in different populations or species (Wood, Burke et al 2005, Martin and Orgogozo 2013). Evolution can target classes of genes that share molecular features such as biochemical (e.g. chemoreceptor genes (Bachmanov and Beauchamp 2007, Keller, Zhuang et al 2007, Wisotsky, Medina et al 2011, Lunde, Egelandsdal et al 2012, McRae, Mainland et al 2012, McBride, Baier et al 2014, Greene, Brown et al 2016, Greene, Dobosiewicz et al 2016)) or developmental function (e.g. master regulators of cell fate (Sucena, Delon et al 2003, Colosimo, Hosemann et al 2005, Chan, Marks et al 2010, Yang, Wang et al 2018)) Another molecular feature predicted to be important for evolution is the ability of genes to produce multiple protein isoforms. The copyright holder for this preprint It is made available under
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