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Mutations in EID1 and LNK2 Caused Light-Conditional Clock Deceleration

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Mutations in EID1 and LNK2 Caused Light-Conditional Clock Deceleration Mutations in EID1 and LNK2 caused light-conditional SEE COMMENTARY clock deceleration during tomato domestication Niels A. Müllera,b,1, Lei Zhanga,1,2, Maarten Koornneefa,c,3, and José M. Jiménez-Gómeza,d,3 aDepartment of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany; bThünen Institute of Forest Genetics, 22927 Grosshansdorf, Germany; cLaboratory of Genetics, Wageningen University, 6708 PB Wageningen, The Netherlands; and dInstitut Jean-Pierre Bourgin, Institut National de la Recherche Agronomique, AgroParisTech, CNRS, Université Paris-Saclay, 78000 Versailles, France Contributed by Maarten Koornneef, April 26, 2018 (sent for review February 1, 2018; reviewed by C. Robertson McClung and Marcelo J. Yanovsky) Circadian period and phase of cultivated tomato (Solanum lyco- Solanum pimpinellifolium (wild tomato ancestor) recombinant persicum) were changed during domestication, likely adapting the inbred line (RIL) population and on the left by an introgression species to its new agricultural environments. Whereas the delayed present in BIL497, a backcross inbred line from a cultivated circadian phase is mainly caused by allelic variation of EID1, the tomato (cv. M82) x Solanum pennellii (wild tomato relative) genetic basis of the long circadian period has remained elusive. population (10, 12, 13) (Fig. 1A and SI Appendix, Fig. S1). Here we show that a partial deletion of the clock gene LNK2 is Analysis of expression profiles, polymorphisms, and functional responsible for the period lengthening in cultivated tomatoes. We descriptions of the 245 annotated genes within the region use resequencing data to phylogenetically classify hundreds of (Solyc01g068160 - Solyc01g080620) did not reveal any obvious tomato accessions and investigate the evolution of the eid1 and candidate gene, and we considered the possibility that the lnk2 mutations along successive domestication steps. We reveal causative gene is present only in the wild tomato species and signatures of selection across the genomic region of LNK2 and has been lost during domestication. We therefore devised a different patterns of fixation of the mutant alleles. Strikingly, method to identify such cases using the reference genome of the LNK2 and EID1 are both involved in light input to the circadian wild tomato relative S. pennellii (14) and transcriptome data from clock, indicating that domestication specifically targeted this input cultivated tomato, its wild ancestor S. pimpinellifolium,andS. pathway. In line with this, we show that the clock deceleration in pennellii (SI Appendix, SI Methods). We identified 11 genes that the cultivated tomato is light-dependent and requires the phyto- are at least partially deleted in cultivated tomato but present and chrome B1 photoreceptor. Such conditional variation in circadian expressed in both wild species (SI Appendix,TableS1). One of rhythms may be key for latitudinal adaptation in a variety of spe- these genes, Solyc01g068560/Sopen01g030520, is located within cies, including crop plants and livestock. the QTL region and shows a deletion of its middle five exons in cultivated tomato that leaves a severely truncated ORF annotated tomato | domestication | circadian rhythms | light signaling | phytochrome as unknown protein (Fig. 1 B and C). Strikingly, the full-length S. pennellii coding sequence unequivocally identified this gene as ircadian clocks are endogenous timekeepers crucial for an Coptimal synchronization of physiological processes with the Significance external environment (1, 2). Although circadian resonance, a clock period closely matched to the 24-h period of the Earth, Internal timekeepers, called circadian clocks, are prevalent in all enhances life span and fitness (3, 4), naturally occurring variation domains of life. Variation in circadian rhythms allows fine-tuning of in circadian rhythms, manifesting as periods deviating from 24 h, an organism to its specific environment. Here we show that a appears to be important for local adaptation. This apparent mutation in LNK2,inadditiontothealreadydescribedmutationin paradox can be found in various organisms (5). For example, EID1, was responsible for the deceleration of circadian rhythms in longer circadian periods seem advantageous at higher latitudes cultivated tomatoes. We show that the mutant alleles of both among natural accessions of Arabidopsis thaliana (6), Mimulus (7), genes arose in the earliest cultivated types and were selected or Drosophila (8, 9). Additionally, adaptive differentiation of cir- during the domestication process. Notably, both mutant alleles cadian rhythms is driven by human selection. Domestication- and specifically affect light input to the clock, leading to a light- breeding-associated variation has been reported for various crop conditional clock deceleration. Such light-conditionality may be a plants (7, 10, 11). In tomato, for example, two mutations led to a widespread means to enhance resonance with changed day–night clock deceleration, likely adapting the cultivated species to the long cycles at higher latitudes, despite the fixed 24-h period of the Earth. summer days it encountered as it was carried away from its equa- torial origin. One of these mutations, a single amino acid de- Author contributions: N.A.M., L.Z., M.K., and J.M.J.-G. designed research; N.A.M. and L.Z. PLANT BIOLOGY EID1 performed research; M.K. contributed new reagents/analytic tools; N.A.M. and J.M.J.-G. letion in , mainly delays the circadian phase, while the analyzed data; and N.A.M. and J.M.J.-G. wrote the paper. other one, not yet identified, primarily lengthens the circadian pe- Reviewers: C.R.M., Dartmouth College; and M.J.Y., Fundación Instituto Leloir. riod (10). Here we identify a near-complete deletion of LNK2 as The authors declare no conflict of interest. the period-lengthening mutation. We provide evidence that this mutation was selected during tomato domestication and reveal its Published under the PNAS license. eid1 Data deposition: The RNA-seq data have been deposited on the NCBI Sequence Read coevolution with . We further demon-strate that the pro- Archive, https://www.ncbi.nlm.nih.gov/sra [accession nos. SRP133995 (phyB mutants) nounced alteration of circadian rhythms in cultivated tomatoes is and SRP124605 (low-resolution light and dark time-courses)]. light-dependent and requires the photoreceptor PHYB1. See Commentary on page 6888. 1 Results N.A.M. and L.Z. contributed equally to this work. 2 LNK2 Present address: Institute of Plant Breeding, Genetics and Genomics, University of Georgia, A Near-Complete Deletion of Is Responsible for the Long Athens, GA 30602. Circadian Period in Cultivated Tomatoes. We previously identified 3To whom correspondence may be addressed. Email: [email protected] or jose. a single genomic region on chromosome 1 responsible for the [email protected]. circadian period lengthening in cultivated tomato (10). This re- This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. gion is delimited on the right by the quantitative trait locus 1073/pnas.1801862115/-/DCSupplemental. (QTL) detected in a cultivated tomato (cv. Moneymaker) x Published online May 22, 2018. www.pnas.org/cgi/doi/10.1073/pnas.1801862115 PNAS | July 3, 2018 | vol. 115 | no. 27 | 7135–7140 Downloaded by guest on September 30, 2021 LOD score 0 1 2 3 4 5 6 7 8 9 10 A Fig. 1. LNK2 colocalizes with the circadian period 123456789101112 QTL and is partially deleted in cultivated tomato. (A) QTL analysis for circadian period in a S. pimpinelli- folium x S. lycopersicum cv. MM RIL population identified a single significant locus on chromosome 1 B (10). Logarithm of the odds (LOD) scores are given * for the 12 tomato chromosomes; the genome-wide 5% significance threshold is 2.9. An introgression 70.0 70.5 71.0 71.5 72.0 line with a precisely defined genomic fragment from Chromosome 1 (Mb) the wild tomato relative S. pennellii (indicated by a C Annotation Sopen01g030520.1 black bar) exhibited the same short-period pheno- type (SI Appendix, Fig. S1) and refined the left bor- Alignment der of the QTL. (B) The 245 genes annotated in the deleted in M82 tomato genome reference v2.4 present in the QTL re- conserved gion are depicted by black arrows; genes deleted in 200 cultivated tomato but present in S. pennellii are shown 100 S. lycopersicum cv M82 coverage 0 in red and marked by an asterisk. (C) From top to 200 bottom: gene model for LNK2 in the wild tomato spe- 100 S. pimpinellifolium coverage cies S. pennellii; graphical output of BLAST results 0 comparing the genomic sequence of S. pennellii and 200 100 S. pennellii cultivated tomato; and coverage plots of RNA-seq reads RNA-seq reads coverage 0 from cultivated tomato (red), S. pimpinellifolium (or- 87.730 87.735 87.740 87.745 ange), and S. pennellii (green), aligned to the S. pen- Chromosome 1 (Mb) nellii reference genome. the homolog of the Arabidopsis circadian clock gene NIGHT evolutionary trajectory of the eid1 and lnk2 mutations during do- LIGHT-INDUCIBLE AND CLOCK-REGULATED 2 (LNK2, mestication and breeding (Fig. 3A and Datasets S2 and S3). Both AT3G54500, SI Appendix,TableS2). The Arabidopsis lnk2 mutations were absent in the wild tomato species, including the wild mutant exhibits a long circadian period (15), suggesting that the ancestor S. pimpinellifolium. They first appeared at low frequencies LNK2 deletion of in cultivated tomato may be responsible for in the most ancient domesticated tomatoes, the Ecuadorian S. the clock deceleration. lycopersicum lnk2 var. cerasiforme accessions (17). However, while the Expression of the truncated transcript in tomato shows a eid1 robust diurnal oscillation with a peak at about 4 h after dawn, as mutation rose to near fixation already in the next step of described for the full-length homologs in Arabidopsis, poplar and rice (16) (SI Appendix,Fig.S2). This oscillation continues under circadian conditions, although with strong dampening in cultivated tomato, as reported for other clock-regulated genes (10) (SI Ap- A Slylnk2 pendix,Fig.S2).
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