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Whole-genome resequencing of 445 Lactuca accessions reveals the domestication history of cultivated lettuce

Nature Genetics volume 53, pages 752–760 (2021)Cite this article

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Abstract

Lettuce (Lactuca sativa) is an important vegetable crop worldwide. Cultivated lettuce is believed to be domesticated from L. serriola; however, its origins and domestication history remain to be elucidated. Here, we sequenced a total of 445 Lactuca accessions, including major lettuce crop types and wild relative species, and generated a comprehensive map of lettuce genome variations. In-depth analyses of population structure and demography revealed that lettuce was first domesticated near the Caucasus, which was marked by loss of seed shattering. We also identified the genetic architecture of other domestication traits and wild introgressions in major resistance clusters in the lettuce genome. This study provides valuable genomic resources for crop breeding and sheds light on the domestication history of cultivated lettuce.

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Fig. 1: Phylogeny and population structure of cultivated lettuce and its wild relative species.
Fig. 2: Proposed domestication center of cultivated lettuce near the Caucasus.
Fig. 3: Identification of selective sweeps associated with domestication traits in cultivated lettuce.
Fig. 4: Introgressive contribution of L. serriola to lettuce resistance breeding.

Data availability

All raw sequencing data were deposited into the Sequence Read Archive (under BioProject accession PRJNA693894) and CNGB Nucleotide Sequence Archive (CNSA; under the accession number CNP0000335). Variant files, genome assemblies and annotation files are stored in CNSA under the same accession number. Source data are provided with this paper.

Code availability

All of the code used in this study is available at https://github.com/popgenome/lettuce2020.

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Acknowledgements

This research was supported by grants from the National Key Research and Development Program of China (2019YFC1711000 to H.L.), Shenzhen Municipal Government of China (JCYJ20170817145512467 to H.L.) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011 to X.X.). The contributions of R.v.T. and T.v.H. were part of the Fundamental Research Programme ‘Circular and Climate Neutral’ (KB-34-013-001) funded by the Dutch Ministry of Agriculture, Nature and Food Quality. We thank S. Feng, S. K. Sahu and T. Chiu (BGI-Shenzhen) for helpful discussion on population structure.

Author information

Author notes

  1. These authors contributed equally: Tong Wei, Rob van Treuren, Xinjiang Liu.

Authors and Affiliations

  1. State Key Laboratory of Agricultural Genomics, BGI-Shenzhen, Shenzhen, China

    Tong Wei, Xinjiang Liu, Zhaowu Zhang, Yang Liu, Ting Yang, Tianming Lan, Xuemei Ni, Jian Wang, Huanming Yang, Xun Xu, Xin Liu & Huan Liu

  2. Centre for Genetic Resources, the Netherlands, Wageningen, the Netherlands

    Rob van Treuren & Theo van Hintum

  3. BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China

    Zhaowu Zhang

  4. Huazhong Agricultural University, Wuhan, China

    Jiongjiong Chen, Peinan Sun & Hanhui Kuang

  5. Fairy Lake Botanical Garden, Shenzhen, China

    Shanshan Dong

  6. University of Copenhagen, Copenhagen, Denmark

    Tianming Lan

  7. BGI-Laos, Vientiane, Laos

    Xiaogang Wang & Zhouquan Xiong

  8. China National GeneBank, Shenzhen, China

    Yaqiong Liu, Jinpu Wei, Haorong Lu, Shengping Han & Jason C. Chen

  9. James D. Watson Institute of Genome Sciences, Hangzhou, China

    Jian Wang & Huanming Yang

  10. Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, China

    Xun Xu

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  1. Tong Wei
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Contributions

H. Liu, Xin Liu, J. Wang, H.Y., X.X., J.C.C. and T.v.H. conceived of the study idea. T.W., Xinjiang Liu, S.H., X.W., Z.X., Yaqiong Liu and J. Wei carried out the sampling process. H. Lu performed the library preparation and sequencing. J.C., P.S. and H.K. performed the RNA-seq and bulked segregant analysis experiments. T.W., Xinjiang Liu, Z.Z., Yang Liu, S.D. and T.Y. performed the analyses. T.W. and R.v.T. drafted the manuscript. T.L., Yang Liu, X.N., H.K., H. Liu and T.v.H. revised the manuscript.

Corresponding authors

Correspondence to Rob van Treuren, Xin Liu or Huan Liu.

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Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Genetics thanks Xiaowu Wang, Aureliano Bombarely and Thomas Schmutzer for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Phylogenetic relationships of the investigated Lactuca species.

Phylogenetic relationships of the investigated Lactuca species. a, A coalescence-based phylogenetic tree inferred from 4,513 single-loci nuclear genes identified from 12 Lactuca species and the outgroup Helianthus annuus. Branches are maximally supported by ASTRAL posterior probability/IQ-TREE bootstrap score/Mrbayes posterior probability unless otherwise indicated. PhyParts pie charts marked on the nodes, with blue, green, red, and gray color represent the gene trees of concordance, top conflict, other conflict, and no signals, respectively. b, A maximum-likelihood phylogenetic tree based on RAxML analysis of 75 plastid genes. Branches are maximally supported by RAxML bootstrap score/MrBayes posterior probability unless otherwise indicated. The primary (GP1), secondary (GP2), and tertiary gene pool (GP3) species are indicated by the species name.

Source data

Extended Data Fig. 2 Population structure of 440 Lactuca accessions.

Population structure of 440 Lactuca accessions. a, Model-based clustering analysis with different numbers of ancestry kinship (K) from 1 to 20. Species names and geographic origins are indicated in two colored bars at the bottom. L. serriola groups from Central Asia, Caucasus, Western Asia, Southern Europe and Eastern Europe are indicated below the color bars, and Turkish and admixed accessions are indicated by arrows. b, Cross-validation errors for each K and those for K from 6 to 20 are shown in the right panel. Each box plot represents the D statistics from 20 independent runs with randomly chosen seeds. The internal line in each box represents the median and the lower and upper hinges represent the 25th and 75th percentiles, respectively. The whiskers represent 1.5 multiplied by the interquartile range, and dots beyond the whiskers are outliers.

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Extended Data Fig. 3 PCA plot of L. sativa and L. serriola accessions.

PCA plot of L. sativa and L. serriola accessions. a-b, PCA plot of L. sativa and L. serriola accessions colored by species (a) and origins (b). c-d, PCA plot of 199 L. serriola accessions showing the first and second components (c), and the third and fourth components (d). Colors denote geographic origins, with Western Europe (WEU) in light green, Southern Europe (SEU) in blue, Central Europe (CEU) in dark green, Western Asia (WAS) in purple, the Caucasus (CAU) in red, Central Asia (CAS) in orange, admixed samples and those with no collection information (other) in gray. The proportions of variance explained by the PCs are presented in the axis legends.

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Extended Data Fig. 4 Linkage disequilibrium decay measured by r2 in four Lactuca species (a), four lettuce crop types (b) and six L. serriola phylogeographic groups (c).

Linkage disequilibrium decay measured by r2 in four Lactuca species (a), four lettuce crop types (b) and six L. serriola phylogeographic groups (c). Six phylogeographic groups of L. serriola include Western Europe (WEU), Southern Europe (SEU), Eastern Europe (CEU), Western Asia (WAS), the Caucasus (CAU), and Central Asia (CAS).

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Extended Data Fig. 5 Change of effective population size (Ne) over time in cultivated and wild lettuce.

Change of effective population size (Ne) over time in cultivated and wild lettuce. a-b, Change of Ne in L. sativa and L. serriola inferred by a SMC++ estimate analysis with two replicates. c-d, Divergence between L. sativa and L. serriola inferred by a SMC++ split analysis with two replicates. SMC++ estimate and split analyses were performed on the same two sets of 30 randomly chosen accessions from each species. A generation was set as 1 and the mutation rate per generation per site as 4×10−8.

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Extended Data Fig. 6 Neighbor-joining trees of L. sativa and L. serriola accessions using genome-wide SNPs (a), and the SNPs associated with leaf morphology (b), seed shattering (c) and leaf vein spine (d).

Neighbor-joining trees of L. sativa and L. serriola accessions using genome-wide SNPs (a), and the SNPs associated with leaf morphology (b), seed shattering (c) and leaf vein spine (d). L. sativa samples are in black, and L. serriola ones are colored according to their geographic origins, with Western Europe (WEU) in light green, Southern Europe (SEU) in blue, Eastern Europe (CEU) in dark green, Western Asia (WAS) in purple, the Caucasus (CAU) in red, Central Asia (CAS) in orange, and admixed samples and those with no collection information (other) in gray. L. serriola accessions close to the L. sativa clade are indicated by black triangles with their accession numbers and country of origin.

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Extended Data Fig. 7 Genome-wide association analysis (GWAS) of flowering time in cultivated lettuce.

Genome-wide association analysis (GWAS) of flowering time in cultivated lettuce. a, Manhattan plot and quantile-quantile plot of GWAS result of flowering time in cultivated lettuce. b, Manhattan plot of GWAS result within Chr. 7:163-166 Mb. Red horizontal dashed line in the Manhattan plot represents the Bonferroni-corrected threshold for genome-wide significance (α = 0.05). Red and blue lines underneath the plot represent genes from the plus and minus DNA strands, respectively. The position of PHYTOCHROME C (PHYC), is indicated by the blue arrow in (a) and the red triangle in (b). c, Genotypes of PHYC in 133 L. sativa accessions. Left color bar represents flowering time. Oilseed lettuce accessions are indicated by arrows on the right. A key variant, Chr. 7:164,643,259 G-to-GA indel that causes frameshift mutation, is indicated by the black box. d, Boxplot of the flowering date in lettuce accessions carrying the reference (blue; n = 84 independent samples) and alternative (ref; n = 49 independent samples) allele. The internal line in each box represents the median and the lower and upper hinges represent the 25th and 75th percentiles, respectively. The whiskers represent 1.5 multiplied by the interquartile range, and dots beyond the whiskers are outliers. Statistical significance is examined by a two-sided Student’s t-test.

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Extended Data Fig. 8 Genome-wide association (GWAS) of anthocyanin biosynthesis in cultivated lettuce.

Genome-wide association (GWAS) of anthocyanin biosynthesis in cultivated lettuce. a-b, Photos of cultivated accessions with various leaf anthocyanin content (a) and flower anthocyanin presence (b). Bar = 5 cm in a; bar = 1 cm in b. c-d, Manhattan plots of quantile-quantile plots of GWAS result of leaf anthocyanin content (c) and flower anthocyanin presence (d). The positions of RED LETTUCE LEAF2 (RLL2) and Anthocyanin synthase (ANS) are indicated by arrows in (c,d). Red horizontal dashed line in the Manhattan plots represents the Bonferroni-corrected threshold for genome-wide significance (. Red horize, Genotypes of RLL2 and ANS in 124 L. sativa accessions recorded with leaf anthocyanin content. Left color bar represents leaf anthocyanin content from low (colored in green) to high (in red). f, Genotypes of ANS in 84 L. sativa accessions recorded with flower anthocyanin presence or absence. Left color bar represents flower anthocyanin absence (colored in green) or presence (in red). A key variant in ANS, A-to-C transition at Chr. 9:152,765,187 that causes a stop codon loss, is indicated by the black box.

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Extended Data Fig. 9 Variants in a downy mildew resistance gene, Dm7.

Variants in a downy mildew resistance gene, Dm7. a, Median-joining network of Dm7 haplotypes in the investigated L. sativa accessions with records of resistance to Bremia lactucae isolate 14 (Bl14). b, Dm7 genotypes in all the L. sativa accessions. Seven haplotypes are indicated in the left. c, A neighbor-joining tree of L. sativa and L. serriola accessions using the 260 SNPs within Dm7. Those showing full resistance to Bl14 are indicated by blue ticks. The Dm7.b clade is indicated by a red arrow. d, Geographic distribution of the tested L. serriola accessions. Colors denote resistance to Bl14 as shown in (a). The world map was drawn using the R/ggplot2 package with the Natural Earth data set (http://www.naturalearthdata.com).

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Extended Data Fig. 10 Proposed lettuce domestication and breeding history.

Proposed lettuce domestication and breeding history. Domestication, improvement, and breeding are indicated by arrows. The photos of cultivated lettuce are in green frames, L. virosa is in a purple frame, SEU and CAU groups of L. serriola are in blue and red frames, respectively. Scale bar, 2 cm. Potential introgression processes are indicated by “×”. qLFD, qSHT and qSPN represent three loci controlling leaf morphology, seed shattering, and leaf spine. The world map was drawn based on the Natural Earth data set (http://www.naturalearthdata.com).

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Wei, T., van Treuren, R., Liu, X. et al. Whole-genome resequencing of 445 Lactuca accessions reveals the domestication history of cultivated lettuce. Nat Genet 53, 752–760 (2021). https://doi.org/10.1038/s41588-021-00831-0

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