II 0.95 DM2 (RPP1) DM3 (At3g61540) b

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1 Table S2. F 2 Segregation Ratios at 16 C, Related to Figure 2 Cross n c Phenotype Model e 2 Locus A Locus B Normal F 1 -like Enhanced d Uk-1/Uk DM2 (RPP1) DM1 (SSI4) a Bla-1/Hh-0 F II 0.95 DM2 (RPP1) DM3 (At3g61540) b Bla-1/Hh-0 F V 0.92 DM9 (ACD6) DM9 (ACD6) TueWa1-2/ICE III 1 DM2 (RPP1) DM4 (RPP8) Dog-4/ICE I 0.57 DM2 (RPP1) DM5 KZ10/Mrk IV 0.23 DM6 (RPP7) DM7 (RPW8) Fei-0/Lerik I 0.15 DM6 (RPP7) DM7 (RPW8) Ey V 0.94 DM8 (RPP4/5) DM8 (RPP4/5) a. Due to the two genetically independent interactions (Bomblies et al., 2007), an F 3 population derived from an F 2 individual with the neutral DM9 (ACD6) allele fixed and the DM2/DM3 incompatibility alleles segregating was used to score the leaf twisting phenotype. b. Late-onset lesioning phenotype that segregates independently of the leaf twisting phenotype. c. If the model has lethal classes that were not countable, n was estimated to include the lethal individuals for 2 calculation. d. More severe than F 1 hybrids. e. Best-fit models using F 2 segregation analyses with incompatibility alleles indicated as "A" and "B". Model for Uk-1/Uk-3 described before (Bomblies et al., 2007). I: two-loci-semi-dominant; F 1 -like genotype was AaBb; stronger genotypes were AABb and AaBB; AABB was lethal and not countable. II: two-loci-semi-dominant; F 1 -like genotype was AaBb; stronger genotype was AABb; AaBB and AABB were lethal and not countable. III: two-loci-semi-dominant; F 1 -like genotype was AaBb; AABb, AaBB and AABB were lethal and not countable. IV: two-loci-semi-dominant; F 1 -like genotypes were AaBb and AaBB; stronger genotype was AABb; AABB was lethal and not countable. V: one-locus-heterozygous disadvantage; F 1 -like genotype was Aa; normal genotypes were AA and aa.

2 Table S3. F 2 Populations for Genetic Mapping, Related to Figure 2 Cross Individuals Markers % of each genotype (± standard deviation) * AA AB BB Uk-1/Uk (±6.5) 47.0 (±9.0) 27.3 (±7.8) Bla-1/Hh (±5.1) 50.6 (±9.1) 23.8 (±9.1) TueWa1-2/ICE (±13.3) 42.0 (±9.9) 27.1 (±9.9) Dog-4/ ICE (±6.1) 43.9 (±6.0) 27.8 (±6.6) KZ10/Mrk (±8.4) 56.2 (±9.2) 19.9 (±7.4) Fei-0/Lerik (±5.7) 50.0 (±7.3) 23.0 (±4.1) Ey (±9.6) 28.3 (±5.1) 30.2 (±9.7) *Average percentage of each genotype at all markers for each population.

3 Table S4. Mapping Intervals for DM Loci, Related to Figure 2 Locus Chromosome Fine-mapping interval* (kb) Start (bp) End (bp) NLRs (At IDs) or non-nlr immunity genes DM2 ICE ,153,632 16,263,309 At3g44630, At3g44670 DM2 Dog ,009,510 16,296,599 At3g44400, At3g44480, At3g44630, At3g44670 DM2 Uk ,143,301 16,291,301 At3g44630, At3g44670 DM2 Bla ,149,004 16,298,401 At3g44630, At3g44670 DM3 Hh ,713,301 22,948,601 None DM4 TueWa ,160,132 17,495,132 At5g43470 DM5 ICE ,889,486 20,479,260 At5g49140 DM6 Lerik ,601,823 21,920,101 At1g58390, At1g58400, At1g58410, At1g58602, At1g58807, At1g58848, At1g59124, At1g59218 DM6 Mrk ,414,864 22,384,489 At1g58390, At1g58400, At1g58410, At1g58602, At1g58807, At1g58848, At1g59124, At1g59218 DM7 KZ ,528,948 18,988,207 RPW8-like DM7 Fei ,577,755 18,934,151 RPW8-like DM8 ICE228/Ey ,276,217 9,803,085 At4g16860, At4g16890, At4g16900, At4g16920, At4g16940, At4g16940, At4g16950, At4g16960 DM9 Bla-1/Hh ,900,000 8,400,000 ACD6 (confirmed by Todesco et al., 2014) *All intervals were determined based on breakpoints of recombinants. Since most have two-gene interactions, informative recombinants were carefully selected with appropriate combinations of two alleles at the interacting loci.

4 Table S5. GENECONV Analyses, Related to Figure 5 Identical Sequence Tracks Identified by GENECONV Pair Genes queried Identical sequence tracks Average/ median length (bp) DM2 Col /64 DM2 Ler /124 DM2 Uk /130 DM2 Bla /117 Gene 1 Gene 2 P- value Identical sequence tracks in DM2 Uk-1 paralogs Start (bp CDS) Length (bp) Polym. sites Mismatches Conversion time* DM2d Uk-1 DM2h Uk DM2d Uk-1 DM2b Uk , DM2e Uk-1 DM2b Uk , DM2g Uk-1 DM2b Uk , DM2d Uk-1 DM2a Uk , DM2e Uk-1 DM2a Uk , DM2e Uk-1 DM2b Uk , DM2c Uk-1 ; DM2d Uk , DM2c Uk-1 DM2e Uk , DM2c Uk-1 DM2g Uk , *1: before first duplication event; 2: after first, before second duplication event; 3: after both duplication events.

5 Table S6. PCR Survey of LRR Polymorphisms in DM2h Bla-1 Type Genes, Related to Figure 5 Accession* Region Presence Type 1 Type 2 Type 3 Type 4 Type 5 Ey1.5-2 Swabia + HKT2-4 Swabia - Nie1-2 Swabia + Rue Swabia - Star-8 Swabia + TueSB30-3 Swabia - Tuescha-9 Swabia + TueV13 Swabia + TueWa1-2 Swabia duplication WalhaesB4 Swabia - ICE163 S. Tyrol - ICE169 S. Tyrol - ICE173 S. Tyrol - ICE181 S. Tyrol + ICE212 S. Tyrol - ICE213 S. Tyrol - ICE216 S. Tyrol - ICE226 S. Tyrol + ICE228 S. Tyrol + ICE79 S. Tyrol + ICE102 S. Italy + ICE104 S. Italy + ICE106 S. Italy + ICE107 S. Italy + ICE111 S. Italy - ICE112 S. Italy - ICE119 S. Italy - ICE120 S. Italy - ICE91 S. Italy + ICE92 S. Italy + ICE93 S. Italy + ICE97 S. Italy - ICE98 S. Italy + ICE60 S. Russia - ICE61 S. Russia + ICE70 S. Russia + ICE71 S. Russia + ICE72 S. Russia - ICE73 S. Russia - ICE75 S. Russia - Agu-1 N. Africa/Iberia + Cdm-0 N. Africa/Iberia - Don-0 N. Africa/Iberia - Fei-0 N. Africa/Iberia + ICE49 N. Africa/Iberia -

6 ICE50 N. Africa/Iberia - Leo-1 N. Africa/Iberia + Nemrut-1 N. Africa/Iberia - Ped-0 N. Africa/Iberia - Pra-6 N. Africa/Iberia + Qui-0 N. Africa/Iberia + Vie-0 N. Africa/Iberia + Bak-2 Caucasus - Bak-7 Caucasus - Dog-4 Caucasus - Istisu-1 Caucasus - Lag2-2 Caucasus + Lerik1-3 Caucasus + Mer-6 Caucasus - Vash-1 Caucasus - Xan-1 Caucasus - Yeg-1 Caucasus - Del-10 E. Europe + ICE1 E. Europe + ICE21 E. Europe + ICE29 E. Europe + ICE33 E. Europe + ICE36 E. Europe + ICE63 E. Europe - ICE7 E. Europe + Kastel-1 E. Europe - Koch-1 E. Europe - ICE127 Central Asia - ICE130 Central Asia - ICE134 Central Asia - ICE138 Central Asia - ICE150 Central Asia - ICE152 Central Asia - ICE153 Central Asia + Sha Central Asia + Hh-0 N. Germany - Col-0 Reference + Type 1: DM2h Bla-1 /At3g44670 type LRR repeats (1, 2, 3, 4, 5, 6, 7+8, 9, 10, 11) as diagramed in Figure S5 Type 2: Insertion between LRR7 and LRR8 Type 3: Deletion between LRR2 and LRR3 Type 4: Deletions between LRR1 and LRR2 and between LRR3 and LRR4 Type 5: Linker variants between NBS and LRR domains Accessions grouping with Bla-1 (Figure 5D) are in boldface. Accessions with polymorphisms but not belonging to any of the five types above have indels in other LRRs. *Geographic regions as defined in (Cao et al., 2011).

7 Table S7. Rescue Experiments with amirnas, Related to Experimental Procedures amirna Sequence Predicted targets Rescue Uk-1/Uk-3 Bla-1/Hh-0 KB209 UGACACAUAA ACUCCAUCGGU DM2b Uk-1, DM2f Uk-1 DM2b Bla-1, DM2c Bla-1, DM2e Bla-1, DM2h Bla-1 No Yes KB211 KB226 KB228 UGUUGGCACA UAAACUCGGAG UUCUUACCGA UCCCAGGCGGU UAUAUCCGUA AUGAUUGCGGC DM2a Uk-1, DM2b Uk-1, DM2f Uk-1 No Partial Bla-1, DM2h Bla-1 DM2a Bla-1, DM2b Bla-1, DM2c Bla-1, DM2e All DM2s Yes No DM2d Uk-1, DM2e Uk-1, DM2g Uk-1 DM2a Bla-1, DM2b Bla-1, DM2c Bla-1, DM2e Bla-1 Yes No EK20 EC290 EC292 EC293 EC294 EC295 UUUUCCAGGU AUUUCAGUCAA UAGAUGACAA GUUGACGUCGA UUAUUUAACC UAUCGUCGCAG UAUCUAUUAA UAGCCCCCCCG UGUCCGCUAC AAUUCGGCCGU UGAAUGGCAA ACGUAUUGCAC At1g58602, At1g58807, At1g59124 At4g16860, At4g16890, At4g16900, At4g16920, At4g16940, At4g16950, At4g16960, At4g16860, At4g16920 At4g16860, At4g16920 At4g16860, At4g16920 At4g16890, At4g16950 Rescued Fei-0/Lerik1-3

8 Table S8. Sequences of Oligonucleotides, Related to Experimental Procedures Gene Primer 1 (5' to 3') Primer 2 (5' to 3') Diagnostic primers for population genetics DM2h Bla-1 type CAC AAT AAA TAT GCA TAC TTT GCT CAG ACA GCA TTC TCC TAT CTT CCA ATT TCG TTT Primers for probes to screen fosmid clones At3g44610 AAA CAA TCT CAG GAG CCA AG AGA GAA CAA TGG CTC TAC GG At3g44630 CTG CCC AGC ACA GAC TAT GA ATG GAC AAT GGA ATG GGG TA At3g44680 CAG GCC AAA GAA TCG AAA AA TGT TTG GTC GGT GGT TTG TA At3g44700 TGA AAG ACA TGT GCG AGG AG AGA AGC AAA GAG GGC AAA CA At3g44730 AAT TTT CTC CGG GTC ATG TA TTA CCG GTT GAG TGT CAA TG HDA in Bla-1 CCC GTG AAC GCT CTG AAA CAT TCA AAC CGT T CGT GAA GAA GTT CAA TCT TCC CTT ACT GGT ATC TAA TCT At3g44480 CGA GTC TTG TCA AGC TCC CAC CAT CTA TC GGA GTA TCC CGC ATT CTC CTA TCT TCC AAT TG At3g61530 CTG AGA AGA TGG TGA ATC TGA ATG ATC CAT CGG TTG ATA CTG CAG TTA GGG TGT TG At3g61620 GCT CGG CGA TAC TCT AGC TGT TTG GT GGT GTT GTG TGA GTA TAG TAT GGC TCA GTT At3g61710 GTT ACA CAT CGT ATG GAG GAG GCG ACT ATC AAT GTC TTA ACT CGT At3g61740 GTC CAT AGT CCT GGT CGG ATT CCG T CGG ACC TTG ACG ACA TTC GAG AAT CAG AAT At3g61790 CTA TCT CCA CCT GAG AAG AAG AGA GCC A CTC GAA TGT CCT GTC TGC ACC AAT TCT ATG TA At3g61400 CAA TAC CTC TGC GTT ACT CCG TTT AGA GAT CCG CAA GCA AAT TCT AAG GTA CTC ATC AAG AAT HR2 (At3g50460) GGA TCA CTC CGT TGG TGA CT CAC GGT CTT TGT TCC GTT TT Primers for qrt-pcr CAA TGA TAA GAA TCA TGC TCA ACA AGA GAG TCA GAG DM2b/c Bla-1 ACT G CCC CAC TAA ACT TGA GCA ACG TCT AAG CTC TAA TTC T DM2e Bla-1 GAA GCT CCC CGC TAT CGA GAA TGC GAC TAA G CCT ATG AGC TTG AGT AGC TTA ATG TGT GTG GAG ATC T DM2h Bla-1 CAG GTA TTG GAT CTC CAT AAT TGC TCA AGT CTA ATA CTC GAG GGA CTT ACA ATT ATC TGC ATA TAT GTA ATA -tubulin-2 (At5g62690) GAG CCT TAC AAC GCT ACT CTG TCT GTC ACA CCA GAC ATA GTA GCA GAA ATC AAG

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