Title: Plasmodium vivax-like genome sequences shed new insights into

Plasmodium vivax biology and evolution

Authors: Aude Gilabert1,#, Thomas D. Otto2,3,#, Gavin G. Rutledge2, Blaise Franzon1,

Benjamin Ollomo3’ Céline Arnathau1, Patrick Durand1, Nancy D. Moukodoum4, Alain-

Prince Okouga4, Barthélémy Ngoubangoye4, Boris Makanga4, Larson Boundenga4,

Christophe Paupy1,4, François Renaud1, Franck Prugnolle1,4,*, Virginie Rougeron1,4,*

Affiliations:

1Laboratoire MIVEGEC (Université de Montpellier-CNRS-IRD), 34394 Montpellier,

FRANCE

2Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10

1SA, UK

3 Institute of Infection, Immunity and Inflammation, University of Glasgow, College of

Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, 120 University Place,

Glasgow G12 8TA, UK

4Centre International de Recherches Médicales de Franceville, B.P. 769, Franceville,

GABON

1 #Contributed equally to this work

*Corresponding authors: Rougeron Virginie; Laboratoire MIVEGEC (UM-CNRS-IRD),

34394 Montpellier, France; [email protected] / [email protected];

Prugnolle Franck; Laboratoire MIVEGEC (UM-CNRS-IRD), 34394 Montpellier, France; [email protected]

Supplementary Figures legends. Supplementary Figure 1. Genome synteny between P. vivax reference genome PvP01 and P. vivax-like genome Pvl01. Top: reference chromosome from Plasmodium vivax PvP01, bottom: Pvl01 genome. Orange = forward strand gene ; Blue = reverse strand gene ; Green = missing core gene ; Black = singleton gene ; Yellow = gap.

Supplementary Figure 2. Genome synteny between P. vivax reference genome PvP01 and P. vivax-like genome Pvl06. Top: reference chromosome from Plasmodium vivax PvP01, bottom: Pvl06 genome. Orange = forward strand gene ; Blue = reverse strand gene ; Green = missing core gene ; Black = singleton gene ; Yellow = gap.

2

Supplementary Figure 1.

Chromosome(1( Chromosome(2( Chromosome(3( Chromosome(4( Chromosome(5(

Chromosome(6( Chromosome(7( Chromosome(8( Chromosome(9( Chromosome(10(

Chromosome(11( Chromosome(12( Chromosome(13( Chromosome(14(

P.#vivax(like#Pvl01# P.#vivax#PvP01#

3

Supplementary Figure 2

Chromosome(1( Chromosome(2( Chromosome(3( Chromosome(4( Chromosome(5(

Chromosome(6( Chromosome(7( Chromosome(8( Chromosome(9( Chromosome(10(

Chromosome(11( Chromosome(12( Chromosome(13( Chromosome(14(

P.#vivax(like#Pvl06# P.#vivax#PvP01#

4 Supplementary Table 1. Sample information for the eleven strains of P. vivax-like, as well as for P. cynomolgi and the 19 human P. vivax samples used in the analysis. NA. Non-Available information.

Plasmodium Year of Sample ID Accession Number Country Plasmodium co-infection Host species Source Usage species collection Plasmodium malariae-like Pan and Plasmodium troglodytes Rutledge et al. Reference P. vivax-like Pvl01 Being subitted Gabon 2012 reichenowi troglodytes 2017 genome Pan troglodytes Gilabert et al. SNP P. vivax-like Pvl02 Being subitted Gabon 2012 Plasmodium gaboni troglodytes Unpublished calling Pan troglodytes Gilabert et al. SNP P. vivax-like Pvl03 Being subitted Gabon 2012 Plasmodium gaboni troglodytes Unpublished calling Pan troglodytes Otto et al. SNP P. vivax-like Pvl04 Being subitted Gabon 2012 Plasmodium gaboni troglodytes Unpublished calling Pan troglodytes Gilabert et al. SNP P. vivax-like Pvl05 Being subitted Gabon 2013 Plasmodium reichenowi troglodytes Unpublished calling Pan troglodytes Otto et al. Reference P. vivax-like Pvl06 Being subitted Gabon 2013 Plasmodium gaboni troglodytes Unpublished genome Pan troglodytes Gilabert et al. SNP P. vivax-like Pvl07 Being subitted Gabon 2013 Plasmodium reichenowi troglodytes Unpublished calling Pan troglodytes Gilabert et al. SNP P. vivax-like Pvl08 Being subitted Gabon 2012 Plasmodium reichenowi troglodytes Unpublished calling Gilabert et al. SNP P. vivax-like Pvl09 Being subitted Gabon 2013 // Anopheles sp. Unpublished calling Pan troglodytes Otto et al. SNP P. vivax-like Pvl10 Being subitted Gabon 2013 Plasmodium gaboni troglodytes Unpublished calling Pan troglodytes Otto et al. SNP P. vivax-like Pvl11 Being subitted Gabon 2012 Plasmodium gaboni troglodytes Unpublished calling Hupalo_etal_2 SNP P. vivax PvBr22 SRR1562939 Brazil 2011 // Homo sapiens 016 calling Hupalo_etal_2 SNP P. vivax PvBr32 SRR1568192 Brazil 2011 // Homo sapiens 016 calling Hupalo_etal_2 SNP P. vivax PvCo01 SRR1568221 Colombia 2012/2013 // Homo sapiens 016 calling Hupalo_etal_2 SNP SRR1738040 P. vivax PvIn01 India 2013 // Homo sapiens 016 calling Hupalo_etal_2 SNP SRR1740345 P. vivax PvIn02 India 2013 // Homo sapiens 016 calling Hupalo_etal_2 SNP P. vivax PvIn03 SRR332913 India 2001 // Homo sapiens 016 calling Madagasc Hupalo_etal_2 SNP P. vivax PvMal08 SRR570031 ar 2010 // Homo sapiens 016 calling Madagasc Hupalo_etal_2 SNP P. vivax PvMal19 SRR572651 ar 2010 // Homo sapiens 016 calling Madagasc Hupalo_etal_2 SNP P. vivax PvMal15 SRR828416 ar 2010 // Homo sapiens 016 calling Mauritani Hupalo_etal_2 SNP P. vivax PvMau SRR332413 a I 1996 // Homo sapiens 016 calling Hupalo_etal_2 SNP P. vivax PvMe01 SRR1568219 Mexico 2002 // Homo sapiens 016 calling Hupalo_etal_2 SNP P. vivax PvMy01 SRR1568204 Myanmar 2012/2013 // Homo sapiens 016 calling Papua New Hupalo_etal_2 SNP P. vivax PvPNG58 SRR1568177 Guinea 2009 // Homo sapiens 016 calling Papua New Hupalo_etal_2 SNP P. vivax PvPNG14 SRR1568185 Guinea 2008 // Homo sapiens 016 calling P. vivax PvPNG12 SRR1759411 Papua 2009 // Homo sapiens Hupalo_etal_2 SNP

5 New 016 calling Guinea Papua New Hupalo_etal_2 SNP P. vivax PvPNG25 SRR1759523 Guinea 2008 // Homo sapiens 016 calling Hupalo_etal_2 SNP P. vivax PvPe03 SRR1759047 Peru 2008 // Homo sapiens 016 calling Hupalo_etal_2 SNP P. vivax PvTh01 SRR1568180 Thailand 2012 // Homo sapiens 016 calling Hupalo_etal_2 SNP P. vivax PvTh02 SRR1568186 Thailand 2012 // Homo sapiens 016 calling DRR000476 & Tachibana et SNP P. cynomolgi PcyB DRR000477 Malaysia 1950 // Homo sapiens al. 2012 calling

6 Supplementary Table 2. Sequencing information for the eleven strains of P. vivax- like. The sequencer used, the read length produced and accession numbers are indicated. The number of reads mapped to the reference strain P. vivax (PvP01), the coverage and the mean depth of sequencing obtained per site are presented. * estimated as the number of properly paired mapped reads * length of the reads / length of the PvP01 reference genome ; ** p1, p5, p10 and p20 refer to the proportion of sites covered by at least 1, 5, 10 and 20 reads respectively.

Read length # properly paired Mean Sample (bp) (paired- Accession reads mapped to depth / name Sequencer end) number PvP01 Coverage* site p1** p5** p10** p20**

Being Pvl01 MiSeq 150 submitted 2914210 15 13.98 0.75 0.64 0.50 0.27

Being Pvl02 HiSeq 2500 100 & 150 submitted 3741968 13 17.31 0.75 0.62 0.49 0.29

Being Pvl03 HiSeq 2500 100 & 150 submitted 20562102 71 87.01 0.81 0.75 0.71 0.64

Being Pvl04 HiSeq 2500 100 & 150 submitted 6959986 24 28.87 0.69 0.51 0.40 0.28

Being Pvl05 HiSeq 2500 100 & 150 submitted 10226562 35 42.47 0.77 0.65 0.56 0.43

Being Pvl06 Pac Bio >1000 submitted 18256700 63 71.69 0.72 0.58 0.50 0.41

Being Pvl07 MiSeq 150 submitted 22378130 77 94.85 0.64 0.50 0.43 0.35

Being Pvl08 HiSeq 2500 100 & 150 submitted 3619100 12 16.56 0.82 0.71 0.58 0.33

Being Pvl09 HiSeq 2500 100 & 150 submitted 24942182 86 103.06 0.94 0.91 0.89 0.85

Being Pvl10 HiSeq 2500 100 & 150 submitted 86181446 297 335.10 0.87 0.81 0.78 0.76

Being Pvl11 HiSeq 2500 100 & 150 submitted 55201456 190 216.84 0.84 0.78 0.76 0.73

7 Supplementary Table 3. P. vivax genome-wide signatures of selection. The branch-site test of positive selection for orthologous genes as well as the P-value for this test are indicated. In orange are indicated genes with significant Dn/Ds ratios between P. vivax and P. vivax-like and in bold the genes with significant Dn/Ds ratios between P. vivax and P. falciparum.

PVP01 gene ID Gene product dN/dS p-value PVP01_0000040 Pvstp1 protein, putative CDS 0,01001687 PVP01_0004280 Plasmodium exported protein, unknown function CDS 1,49341E-07 PVP01_0103700 erythrocyte membrane-associated antigen,putative CDS 4,02555E-05 PVP01_0104400 tRNA m5C-methyltransferase, putative CDS 4,64361E-13 PVP01_0105800 RNA helicase, putative CDS 1,71882E-05 PVP01_0106100 ATP synthase lipid-binding protein,mitochondrial precursor, putative CDS 0,016906848 PVP01_0107400 conserved Plasmodium protein, unknown function CDS 0,000127702 PVP01_0107600 AAA family ATPase, putative CDS 0,013232349 PVP01_0108900 inner membrane complex protein 1d, putative CDS 5,30547E-05 PVP01_0110000 lysophospholipase, putative CDS 0,025292082 PVP01_0110400 conserved Plasmodium protein, unknown function CDS 0,00170832 PVP01_0113600 vacuolar proton translocating ATPase subunit A,putative CDS 0,014060033 PVP01_0114200 ferlin, putative CDS 3,65308E-08 PVP01_0114300 C-mannosyltransferase, putative CDS 1,34058E-08 PVP01_0114400 conserved Plasmodium protein, unknown function CDS 4,73955E-05 PVP01_0115500 alpha/beta , putative CDS 3,63702E-13 PVP01_0115700 peptidyl-prolyl cis-trans precursor,putative cyclophilin, putative CDS 0,001759144 PVP01_0115900 U2 snRNA/tRNA pseudouridine synthase, putative CDS 0,007524784 PVP01_0116200 conserved Plasmodium protein, unknown function CDS 1,48291E-05 PVP01_0116300 cactin homolog, putative CDS 1,17561E-38 PVP01_0116900 mitogen-activated protein kinase organizer 1,putative CDS 6,7204E-05 PVP01_0118000 1-cys peroxiredoxin CDS 0,007479824 PVP01_0118300 conserved Plasmodium protein, unknown function CDS 0,033591266 PVP01_0118700 nucleolar protein 10, putative CDS 0,000654952 PVP01_0201200 Plasmodium exported protein, unknown function CDS 0,002235939 PVP01_0204000 conserved Plasmodium protein, unknown function CDS 3,9543E-07 PVP01_0204600 bromodomain protein, putative CDS 2,00569E-55 PVP01_0204900 selenocysteine-specific elongation factor selBhomologue, putative CDS 0,001884982 PVP01_0205300 phenylalanine--tRNA alpha subunit,putative CDS 0,031149436 PVP01_0206900 proteasome subunit beta type-3, putative CDS 1,31827E-11 PVP01_0207100 double-strand break repair protein MRE11,putative CDS 1,58648E-11 PVP01_0207600 carbon catabolite repressor protein 4, putative CDS 0,023069051 PVP01_0208600 conserved Plasmodium protein, unknown function CDS 0,010309451 PVP01_0208800 conserved Plasmodium protein, unknown function CDS 1,26039E-08 PVP01_0209500 cyclase-associated protein, putative CDS 1,0986E-08 PVP01_0214500 conserved Plasmodium protein, unknown function CDS 0,000756002 PVP01_0214700 signal recognition particle subunit SRP9,putative CDS 0,01132154

8 PVP01_0216800 Plasmodium exported protein, unknown function CDS 0,017860607 PVP01_0303400 transcription factor with AP2 domain(s),putative CDS 0,000784244 PVP01_0304000 conserved Plasmodium protein, unknown function CDS 0,000137314 PVP01_0304800 pre-mRNA-processing-splicing factor 8, putative CDS 9,24173E-05 PVP01_0305300 apical sushi protein rhoptry neck protein 1 CDS 0,030892185 PVP01_0306000 conserved Plasmodium protein, unknown function CDS 0,00469944 PVP01_0306400 methyltransferase, putative CDS 0,004645356 PVP01_0306900 conserved Plasmodium protein, unknown function CDS 0,019260652 PVP01_0307000 conserved Plasmodium protein, unknown function CDS 1,11143E-22 PVP01_0307800 flap 1, putative CDS 0,002714684 PVP01_0308400 U4/U6 small nuclear ribonucleoprotein PRP31,putative CDS 0,000104034 PVP01_0308500 protein SOF1, putative CDS 3,76156E-11 PVP01_0309100 zinc finger protein, putative CDS 0,004197304 PVP01_0309300 erythrocyte vesicle protein 1, putative CDS 0,010136496 PVP01_0310700 DEAD box ATP-dependent RNA helicase, putative CDS 4,46886E-05 PVP01_0313000 conserved Plasmodium protein, unknown function CDS 0,002213285 PVP01_0313800 dynein heavy chain, putative CDS 2,98163E-14 PVP01_0313900 exported serine/threonine protein kinase,putative CDS 1,60006E-05 PVP01_0314000 cysteine repeat modular protein 2, putative CDS 1,12218E-22 PVP01_0314500 conserved Plasmodium protein, unknown function CDS 2,28856E-05 PVP01_0314600 conserved Plasmodium protein, unknown function CDS 4,49811E-20 PVP01_0318000 ubiquitin C-terminal hydrolase, putative CDS 0,003942648 PVP01_0318600 conserved Plasmodium protein, unknown function CDS 3,48255E-21 PVP01_0318900 conserved Plasmodium protein, unknown function CDS 7,26811E-07 PVP01_0319900 type 2A -associated protein 42,putative CDS 0,021633191 PVP01_0320800 conserved Plasmodium protein, unknown function CDS 0,049236899 PVP01_0321000 conserved Plasmodium protein, unknown function CDS 3,80186E-12 PVP01_0404700 Plasmodium exported protein, unknown function CDS 0,000195013 PVP01_0406900 conserved Plasmodium protein, unknown function CDS 0,000100559 PVP01_0407800 conserved Plasmodium protein, unknown function CDS 6,95791E-14 PVP01_0408500 conserved Plasmodium protein, unknown function CDS 1,11053E-09 PVP01_0408900 conserved Plasmodium protein, unknown function CDS 3,18468E-45 PVP01_0410100 conserved Plasmodium protein, unknown function CDS 0,000217934 PVP01_0411500 protein kinase 7, putative CDS 1,03219E-09 PVP01_0412400 conserved Plasmodium protein, unknown function CDS 0,000151354 PVP01_0413500 GAF domain-related protein, putative CDS 0,020389274 PVP01_0415100 RING zinc finger protein, putative CDS 1,19934E-07 PVP01_0415600 3', putative CDS 3,41896E-10 PVP01_0416500 conserved Plasmodium protein, unknown function CDS 2,77854E-53 PVP01_0418400 merozoite surface protein 5 CDS 0,038236557 PVP01_0420100 conserved Plasmodium protein, unknown function CDS 4,28058E-05 PVP01_0504400 sporozoite invasion-associated protein 2,putative CDS 0,000113894 PVP01_0505700 conserved Plasmodium protein, unknown function CDS 0,000365643 PVP01_0506300 conserved Plasmodium protein, unknown function CDS 0,011880084 PVP01_0507300 translation initiation factor IF-2, putative CDS 0,002567763

9 PVP01_0511100 RNA-binding protein, putative CDS 7,30786E-23 PVP01_0511900 conserved Plasmodium protein, unknown function CDS 1,23874E-31 PVP01_0513300 conserved Plasmodium protein, unknown function CDS 0,000560452 PVP01_0513500 conserved Plasmodium protein, unknown function CDS 0,000105686 PVP01_0517200 zinc finger protein, putative CDS 7,3822E-07 PVP01_0522200 conserved Plasmodium protein, unknown function CDS 0,000111657 PVP01_0522300 RING zinc finger protein, putative CDS 0,011307637 PVP01_0526800 conserved Plasmodium protein, unknown function CDS 4,38185E-06 PVP01_0527300 conserved Plasmodium protein, unknown function CDS 0,00143388 PVP01_0529800 transcription factor with AP2 domain(s),putative CDS 0,006086457 PVP01_0530900 40S ribosomal protein S19, putative CDS 2,37296E-06 PVP01_0531400 conserved Plasmodium protein, unknown function CDS 7,94413E-14 PVP01_0532700 tryptophan-rich antigen tryptophan-rich protein CDS 0,028570008 PVP01_0602100 early transcribed membrane protein CDS 0,001065952 PVP01_0603000 conserved Plasmodium protein, unknown function CDS 0,006993024 PVP01_0603200 tRNA pseudouridine synthase, putative CDS 0,042153457 PVP01_0603400 serine/threonine 8,putative CDS 0,000929966 PVP01_0603900 conserved Plasmodium protein, unknown function CDS 0,000707363 PVP01_0605600 S-adenosyl-L-methionine-dependentmethyltransferase, putative CDS 0,002315561 PVP01_0605800 conserved Plasmodium protein, unknown function CDS 0,000958601 PVP01_0606300 conserved Plasmodium protein, unknown function CDS 0,023302832 PVP01_0607100 conserved Plasmodium protein, unknown function CDS 0,030670346 PVP01_0607600 serine/arginine-rich splicing factor 4,putative CDS 0,001258812 PVP01_0609300 conserved Plasmodium protein, unknown function CDS 1,00437E-06 PVP01_0609600 conserved Plasmodium protein, unknown function CDS 6,4969E-10 PVP01_0610000 conserved Plasmodium protein, unknown function CDS 0,003126 PVP01_0610200 formin 2, putative CDS 3,71304E-06 PVP01_0610700 conserved Plasmodium protein, unknown function CDS 0,023652244 PVP01_0611800 conserved Plasmodium protein, unknown function CDS 2,31076E-05 PVP01_0612200 U3 small nucleolar ribonucleoprotein proteinMPP10, putative CDS 0,013944517 PVP01_0612300 mitochondrial ribosomal protein S22 precursor,putative CDS 0,030620529 PVP01_0614900 RAP protein, putative CDS 0,00451667 PVP01_0615500 conserved Plasmodium protein, unknown function CDS 0,025752177 PVP01_0617800 conserved Plasmodium protein, unknown function CDS 1,27893E-07 PVP01_0620200 conserved Plasmodium protein, unknown function CDS 0,001748206 PVP01_0620500 conserved Plasmodium protein, unknown function CDS 0,015163029 PVP01_0621800 conserved Plasmodium protein, unknown function CDS 2,39533E-11 PVP01_0624000 PIR protein VIR protein CDS 0,000580211 PVP01_0701700 conserved Plasmodium protein, unknown function CDS 0,00080269 PVP01_0703500 nucleoporin NUP100/NSP100, putative CDS 0,001860249 PVP01_0703600 mitochondrial carrier protein, putative CDS 1,45632E-06 PVP01_0703800 high molecular weight rhoptry protein 3 CDS 0,039570968 PVP01_0704200 conserved Plasmodium protein, unknown function CDS 0,00138722 PVP01_0704500 exoribonuclease II, putative CDS 0,01004593 PVP01_0705400 tubulin-specific chaperone, putative CDS 0,003023047

10 PVP01_0705700 GTPase-activating protein, putative CDS 0,005686612 PVP01_0707400 conserved Plasmodium protein, unknown function CDS 0,029797658 PVP01_0708700 conserved Plasmodium protein, unknown function CDS 1,1566E-07 PVP01_0710300 conserved Plasmodium protein, unknown function CDS 0,006031866 PVP01_0712000 conserved Plasmodium protein, unknown function CDS 0,000357155 PVP01_0712100 conserved Plasmodium protein, unknown function CDS 0,00052521 PVP01_0712400 pseudouridylate synthase, putative CDS 0,000118791 PVP01_0712900 conserved Plasmodium protein, unknown function CDS 0,000119051 PVP01_0713600 H2 subunit C, putative CDS 0,009533207 PVP01_0713800 6-phosphofructokinase, putative CDS 0,020392827 PVP01_0715800 conserved Plasmodium protein, unknown function CDS 0,039788049 PVP01_0719000 conserved Plasmodium protein, unknown function CDS 6,47186E-10 PVP01_0720000 conserved Plasmodium protein, unknown function CDS 0,000553902 PVP01_0720200 conserved Plasmodium protein, unknown function CDS 0,022492445 PVP01_0723100 conserved Plasmodium protein, unknown function CDS 0,009347277 PVP01_0723600 conserved Plasmodium protein, unknown function CDS 0,000294697 PVP01_0724800 protein kinase, putative CDS 3,41274E-06 PVP01_0725000 conserved Plasmodium protein, unknown function CDS 0,010093466 PVP01_0725100 conserved Plasmodium protein, unknown function CDS 8,08731E-10 PVP01_0725300 conserved Plasmodium protein, unknown function CDS 0,022230983 PVP01_0725600 conserved Plasmodium protein, unknown function CDS 0,020431627 PVP01_0725700 zinc finger protein, putative CDS 7,5848E-12 PVP01_0725900 conserved Plasmodium protein, unknown function CDS 1,23294E-12 PVP01_0726800 conserved Plasmodium protein, unknown function CDS 1,3623E-05 PVP01_0727600 conserved Plasmodium protein, unknown function CDS 3,46594E-06 PVP01_0727800 conserved Plasmodium protein, unknown function CDS 0,037201657 PVP01_0728900 merozoite surface protein 1 CDS 0,015475723 PVP01_0730000 conserved Plasmodium protein, unknown function CDS 0,017402836 PVP01_0803000 ribosome-binding factor A, putative CDS 0,018422352 PVP01_0804500 ADP/ATP carrier protein, putative CDS 0,003116311 PVP01_0805200 regulator of nonsense transcripts 1, putative CDS 0,000344348 PVP01_0811900 PRE-binding protein, putative CDS 0,002560199 PVP01_0812100 E3 ubiquitin-protein ligase, putative CDS 8,23898E-05 PVP01_0813000 autophagy-related protein 18, putative CDS 0,000284124 PVP01_0814600 conserved Plasmodium protein, unknown function CDS 0,025996013 PVP01_0816700 survival motor neuron-like protein, putative CDS 6,89393E-18 PVP01_0817800 D123 (regulator of eIF2), putative CDS 0,046328006 PVP01_0818500 microtubule and actin binding protein, putative CDS 1,03115E-07 PVP01_0818800 protein kinase, putative CDS 2,71248E-31 PVP01_0820800 kinesin-8, putative CDS 0,048121774 PVP01_0821500 cleavage and polyadenylation specificity factor,putative CDS 0,049106641 PVP01_0821600 conserved Plasmodium protein, unknown function CDS 0,002884509 PVP01_0821900 DNA-directed RNA polymerase II subunit RPB1,putative CDS 0,000439526 PVP01_0822000 stomatin-like protein CDS 0,036970287 PVP01_0823600 kinetochore protein NUF2, putative CDS 0,012069316

11 PVP01_0823700 conserved Plasmodium protein, unknown function CDS 0,001063353 PVP01_0824500 zinc finger protein, putative CDS 0,000636961 PVP01_0825200 conserved Plasmodium protein, unknown function CDS 0,000124234 PVP01_0825400 zinc finger protein, putative CDS 0,00062988 PVP01_0829700 ATP-dependent RNA helicase DHX57, putative CDS 3,64282E-35 PVP01_0830900 N2227-like protein, putative CDS 1,49594E-05 PVP01_0831300 splicing factor 3B subunit 1, putative CDS 0,008029315 PVP01_0831700 activator of Hsp90 ATPase, putative CDS 0,045801391 PVP01_0832800 ATP-dependent Clp protease proteolytic subunit,putative CDS 0,03158503 PVP01_0834100 conserved Plasmodium protein, unknown function CDS 0,001017414 PVP01_0835100 conserved Plasmodium protein, unknown function CDS 2,90338E-06 PVP01_0835400 conserved Plasmodium protein, unknown function CDS 0,042434678 PVP01_0835500 conserved Plasmodium protein, unknown function CDS 0,00028415 PVP01_0835600 circumsporozoite (CS) protein CDS 2,45723E-06 PVP01_0836100 inner membrane complex protein 1e, putative CDS 0,012541634 PVP01_0837000 HAD superfamily protein, putative CDS 0,01903534 PVP01_0904200 FeS cluster assembly protein SufD, putative CDS 0,018927235 PVP01_0907100 , putative CDS 0,000534827 PVP01_0907300 conserved Plasmodium protein, unknown function CDS 2,34023E-05 PVP01_0908900 conserved Plasmodium protein, unknown function CDS 1,30063E-09 PVP01_0911200 asparagine-rich antigen, putative CDS 0,000535301 PVP01_0911300 vacuolar protein sorting-associated protein 35,putative CDS 0,020409924 PVP01_0912900 conserved Plasmodium protein, unknown function CDS 4,02923E-08 PVP01_0913800 conserved Plasmodium protein, unknown function CDS 0,006574747 PVP01_0915500 glycerol-3-phosphate dehydrogenase, putative CDS 0,0094711 PVP01_0915600 conserved Plasmodium protein, unknown function CDS 1,20719E-07 PVP01_0916800 pyridoxine biosynthesis protein PDX2, putative CDS 5,46785E-14 PVP01_0917100 folate transporter 2, putative CDS 4,5859E-34 PVP01_0917300 dipeptidyl aminopeptidase 1, putative CDS 8,04547E-10 PVP01_0918500 conserved Plasmodium protein, unknown function CDS 0,045214253 PVP01_0918600 conserved Plasmodium protein, unknown function CDS 0,002288708 PVP01_0918800 heat shock protein 90, putative CDS 0,004770319 PVP01_0919800 conserved protein, unknown function CDS 0,004164688 PVP01_0920300 conserved Plasmodium protein, unknown function CDS 0,000660997 PVP01_0920500 conserved Plasmodium protein, unknown function CDS 0,011453187 PVP01_0921200 conserved Plasmodium protein, unknown function CDS 0,026471323 PVP01_0921400 conserved Plasmodium protein, unknown function CDS 2,33083E-06 PVP01_0921900 tyrosine kinase-like protein, putative CDS 3,91186E-21 PVP01_0923500 dynein heavy chain, putative CDS 3,3423E-06 PVP01_0925500 hypothetical protein CDS 2,41127E-06 PVP01_0926000 DNA-directed RNA polymerase, putative CDS 4,61251E-05 PVP01_0926800 autophagy-related protein 7, putative CDS 3,10166E-14 PVP01_0931300 conserved Plasmodium protein, unknown function CDS 0,015790648 PVP01_0931500 structural maintenance of chromosomes protein 1,putative CDS 0,033291025 PVP01_0935400 zinc finger protein, putative CDS 0,000266927

12 PVP01_0936900 conserved Plasmodium protein, unknown function CDS 0,010262555 PVP01_0940200 AAA family ATPase, putative CDS 0,001003604 PVP01_0941300 conserved Plasmodium protein, unknown function CDS 0,017854065 PVP01_0941500 conserved Plasmodium protein, unknown function CDS 0,017171304 PVP01_0941800 conserved Plasmodium protein, unknown function CDS 0,002391339 PVP01_0943300 60S ribosomal protein L35ae, putative CDS 0,02298093 PVP01_0944500 conserved Plasmodium protein, unknown function CDS 0,000387723 PVP01_0946000 cysteine-rich PDZ-binding protein, putative CDS 0,000808042 PVP01_0947400 conserved Plasmodium protein, unknown function CDS 0,007275959 PVP01_1004100 conserved Plasmodium protein, unknown function CDS 0,048133346 PVP01_1008600 structural maintenance of chromosomes protein 6,putative CDS 2,77226E-06 PVP01_1010200 conserved Plasmodium protein, unknown function CDS 0,010085127 PVP01_1012000 conserved Plasmodium protein, unknown function CDS 5,20563E-16 PVP01_1013500 conserved Plasmodium protein, unknown function CDS 0,037851697 PVP01_1015400 ATP-dependent RNA helicase DDX23, putative CDS 9,5619E-30 PVP01_1016800 conserved Plasmodium protein, unknown function CDS 1,78363E-09 PVP01_1018300 conserved Plasmodium protein, unknown function CDS 0,003361933 PVP01_1018400 amino acid transporter, putative CDS 0,012919819 PVP01_1018500 conserved Plasmodium protein, unknown function CDS 0,000124424 PVP01_1018600 phosphatidylinositol 3-kinase, putative CDS 0,011073573 PVP01_1020700 conserved Plasmodium protein, unknown function CDS 0,010535684 PVP01_1021100 conserved Plasmodium protein, unknown function CDS 0,001968632 PVP01_1024900 structural maintenance of chromosomes protein 4,putative CDS 0,027980962 PVP01_1025500 guanidine nucleotide exchange factor, putative CDS 0,019846275 PVP01_1027900 60S ribosomal subunit protein L24, putative CDS 1,15641E-16 PVP01_1028900 trafficking protein particle complex subunit 8,putative CDS 4,05165E-13 PVP01_1033300 anaphase promoting complex subunit, putative CDS 0,003529893 PVP01_1105000 suppressor of kinetochore protein 1, putative CDS 3,95392E-12 PVP01_1108300 conserved Plasmodium protein, unknown function CDS 0,03670865 PVP01_1109600 calpain, putative CDS 0,007933015 PVP01_1111500 conserved Plasmodium protein, unknown function CDS 0,000321923 PVP01_1114300 conserved Plasmodium protein, unknown function CDS 5,68898E-07 PVP01_1116700 RAP protein, putative CDS 0,000220892 PVP01_1126700 leucine--tRNA ligase, putative CDS 0,00271921 PVP01_1127300 tRNA modifying , putative CDS 1,65515E-18 PVP01_1128400 conserved Plasmodium protein, unknown function CDS 0,001628212 PVP01_1128500 conserved Plasmodium protein, unknown function CDS 0,000343381 PVP01_1128900 conserved Plasmodium protein, unknown function CDS 0,04784466 PVP01_1131400 conserved Plasmodium protein, unknown function CDS 0,004352329 PVP01_1133700 ribonuclease, putative CDS 2,90377E-11 PVP01_1134400 conserved Plasmodium protein, unknown function CDS 0,043288909 PVP01_1135100 thiamin-phosphate pyrophosphorylase, putative CDS 0,038047889 PVP01_1135800 rhoptry protein ROP14, putative CDS 4,65217E-09 PVP01_1137400 conserved Plasmodium protein, unknown function CDS 0,02517919 PVP01_1138400 transketolase, putative CDS 0,004917428

13 PVP01_1138800 RNA-binding protein 25, putative CDS 0,000270219 PVP01_1139600 conserved Plasmodium protein, unknown function CDS 0,020821326 PVP01_1141200 GTP-binding protein, putative CDS 0,007458311 PVP01_1141800 RING zinc finger protein, putative CDS 5,66982E-07 PVP01_1142300 conserved Plasmodium protein, unknown function CDS 0,045174207 PVP01_1144500 conserved Plasmodium protein, unknown function CDS 0,018239214 PVP01_1145000 conserved Plasmodium protein, unknown function CDS 0,004402848 PVP01_1145300 conserved Plasmodium protein, unknown function CDS 3,21527E-12 PVP01_1146800 ATP-dependant RNA helicase, putative CDS 0,000702343 PVP01_1147300 conserved Plasmodium protein, unknown function CDS 0,000793108 PVP01_1202100 P-loop containing nucleoside triphosphatehydrolase, putative CDS 1,32103E-06 PVP01_1202800 conserved Plasmodium protein, unknown function CDS 1,36502E-08 PVP01_1204300 conserved Plasmodium protein, unknown function CDS 0,024667162 PVP01_1204500 conserved Plasmodium protein, unknown function CDS 0,000261473 PVP01_1205700 nucleoside diphosphate hydrolase, putative CDS 2,35884E-12 PVP01_1206000 E1-E2 ATPase, putative CDS 0,008621311 PVP01_1206400 conserved Plasmodium protein, unknown function CDS 5,55356E-10 PVP01_1206600 step II splicing factor, putative CDS 0,035794293 PVP01_1209900 conserved Plasmodium protein, unknown function CDS 0,00023426 PVP01_1210100 conserved Plasmodium protein, unknown function CDS 2,67638E-05 PVP01_1210200 lipoyl synthase, putative CDS 0,037852898 PVP01_1215100 conserved Plasmodium protein, unknown function CDS 0,006619272 PVP01_1215400 conserved Plasmodium protein, unknown function CDS 0,004767811 PVP01_1216600 26S proteasome regulatory subunit RPN3,putative CDS 0,018953725 PVP01_1216700 conserved Plasmodium protein, unknown function CDS 0,007923136 PVP01_1217000 conserved Plasmodium protein, unknown function CDS 7,23856E-05 PVP01_1217400 exonuclease, putative CDS 6,74015E-12 PVP01_1217800 tryptophan--tRNA ligase, putative CDS 1,14271E-07 PVP01_1220800 conserved Plasmodium protein, unknown function CDS 0,00750817 PVP01_1221100 U3 small nucleolar RNA-associated protein 4,putative CDS 0,013932075 PVP01_1221500 ubiquitin-activating enzyme, putative CDS 1,87627E-06 PVP01_1224700 conserved Plasmodium protein, unknown function CDS 0,00066212 PVP01_1225500 DNA-directed RNA polymerase III subunit RPC1,putative CDS 9,36658E-07 PVP01_1226200 conserved Plasmodium protein, unknown function CDS 0,024614798 PVP01_1227600 syntaxin, Qa-SNARE family, putative CDS 0,011182578 PVP01_1229200 conserved Plasmodium protein, unknown function CDS 3,82526E-07 PVP01_1230800 vacuolar protein sorting-associated protein 52,putative CDS 0,006010953 PVP01_1233500 conserved Plasmodium protein, unknown function CDS 0,001981391 PVP01_1234000 conserved Plasmodium protein, unknown function CDS 0,015002145 PVP01_1236700 conserved Plasmodium protein, unknown function CDS 4,61074E-09 PVP01_1240000 conserved Plasmodium protein, unknown function CDS 4,07261E-07 PVP01_1241500 tRNA 3'-trailer sequence RNase, putative CDS 0,033082551 PVP01_1241700 conserved Plasmodium protein, unknown function CDS 0,000119787 PVP01_1242100 ATP synthase (C/AC39) subunit, putative vacuolar ATP synthase subunit d, putative CDS 0,001636957 PVP01_1242900 conserved Plasmodium protein, unknown function CDS 5,83164E-29

14 PVP01_1244000 glyceraldehyde-3-phosphate dehydrogenase,putative CDS 6,69366E-05 PVP01_1244100 cytochrome c1 precursor, putative CDS 7,0417E-13 PVP01_1244300 conserved Plasmodium protein, unknown function CDS 1,83343E-05 PVP01_1244700 conserved Plasmodium protein, unknown function CDS 3,13023E-07 PVP01_1245800 conserved Plasmodium protein, unknown function CDS 0,000238336 PVP01_1246300 conserved Plasmodium protein, unknown function CDS 2,56985E-09 PVP01_1247700 WD repeat-containing protein, putative CDS 0,035735251 PVP01_1247800 GTP-binding protein, putative CDS 2,09397E-08 PVP01_1247900 ATP-dependent RNA helicase DBP5, putative CDS 0,000394461 PVP01_1249000 conserved Plasmodium protein, unknown function CDS 8,14837E-06 PVP01_1250600 conserved Plasmodium protein, unknown function CDS 0,003673317 PVP01_1252700 serine/threonine protein kinase KIN, putative CDS 0,000756396 PVP01_1253400 RAP protein, putative CDS 0,001032756 PVP01_1255600 transcriptional regulatory protein sir2b,putative CDS 0,037247001 PVP01_1258300 conserved Plasmodium protein, unknown function CDS 0,00751054 PVP01_1259100 ABC transporter B family member 2, putative multidrug resistance protein 2, putative CDS 0,007610788 PVP01_1260900 conserved Plasmodium protein, unknown function CDS 1,95729E-12 PVP01_1263500 poly(A)-specific ribonuclease PARN, putative CDS 0,028911053 PVP01_1265300 metalloprotease, putative CDS 0,027177554 PVP01_1266600 conserved Plasmodium protein, unknown function CDS 0,013142146 PVP01_1270700 conserved Plasmodium protein, unknown function CDS 0,021795031 PVP01_1271000 early transcribed membrane protein CDS 0,018620772 PVP01_1300700 Plasmodium exported protein, unknown function CDS 1,45568E-07 PVP01_1303300 conserved Plasmodium protein, unknown function CDS 0,009443647 PVP01_1304100 conserved Plasmodium protein, unknown function CDS 3,88475E-20 PVP01_1304900 high mobility group protein B3, putative CDS 3,2487E-12 PVP01_1307500 amino acid transporter, putative CDS 0,008332083 PVP01_1308700 porphobilinogen deaminase, putative CDS 0,000889614 PVP01_1310400 conserved Plasmodium protein, unknown function CDS 0,006080068 PVP01_1310600 heat shock protein DNAJ homologue Pfj4,putative DnaJ domain containing protein CDS 3,14634E-11 PVP01_1311800 succinyl-CoA ligase, putative CDS 0,034729688 PVP01_1311900 conserved Plasmodium protein, unknown function CDS 4,4639E-06 PVP01_1313900 conserved Plasmodium protein, unknown function CDS 0,004512011 PVP01_1316100 conserved Plasmodium protein, unknown function CDS 3,19649E-13 PVP01_1317400 voltage-dependent anion-selective channelprotein, putative CDS 0,000147963 PVP01_1317900 mitogen-activated protein kinase 1, putative CDS 0,002333491 PVP01_1319000 autophagy protein 5, putative CDS 0,005435462 PVP01_1319500 ADP-dependent DNA helicase RecQ, putative CDS 0,033358481 PVP01_1319600 coatamer protein, beta subunit, putative CDS 1,5243E-07 PVP01_1320000 rRNA (adenosine-2'-O-)-methyltransferase,putative CDS 1,24193E-09 PVP01_1320300 50S ribosomal protein L15, putative CDS 0,000337572 PVP01_1320500 conserved Plasmodium protein, unknown function CDS 0,026317362 PVP01_1321000 proliferation-associated protein 2g4, putative CDS 2,46501E-09 PVP01_1321200 WW domain-binding protein 11, putative CDS 0,022565043 PVP01_1323500 conserved Plasmodium protein, unknown function CDS 1,87867E-07

15 PVP01_1323900 DEAD/DEAH box helicase, putative CDS 5,11979E-06 PVP01_1324000 conserved Plasmodium protein, unknown function CDS 0,001080098 PVP01_1325400 calcium-dependent protein kinase, putative CDS 0,002097215 PVP01_1325900 ankyrin, putative CDS 6,71146E-07 PVP01_1328400 conserved Plasmodium protein, unknown function CDS 0,033168203 PVP01_1328700 tetratricopeptide repeat family protein,putative CDS 6,55086E-09 PVP01_1331300 conserved Plasmodium protein, unknown function CDS 8,5881E-06 PVP01_1331500 rap guanine nucleotide exchange factor,putative CDS 0,001985306 PVP01_1331700 NOT family protein, putative CDS 0,000381685 PVP01_1334000 ATP-dependent protease, putative CDS 0,004833476 PVP01_1334200 ubiquitin carboxyl-terminal hydrolase, putative CDS 1,29372E-05 PVP01_1335600 conserved Plasmodium protein, unknown function CDS 3,42502E-10 PVP01_1337900 conserved Plasmodium protein, unknown function CDS 3,41093E-17 PVP01_1340800 transcription factor with AP2 domain(s),putative CDS 5,98019E-13 PVP01_1346400 U1 small nuclear ribonucleoprotein C, putative CDS 0,041678167 PVP01_1403600 ATP-dependent RNA helicase DHR1, putative CDS 0,027154607 PVP01_1413800 eukaryotic translation initation factor 4 gamma,putative CDS 1,82034E-26 PVP01_1414400 conserved Plasmodium protein, unknown function CDS 0,026960606 PVP01_1417000 inositol polyphosphate kinase, putative CDS 0,013440301 PVP01_1419500 conserved Plasmodium protein, unknown function CDS 0,047342229 PVP01_1420200 N(2),N(2)-dimethylguanosine tRNAmethyltransferase, putative CDS 2,89601E-05 PVP01_1422900 negative elongation factor A, putative CDS 2,82245E-08 PVP01_1424700 GTP-binding translation elongation factor tufamily protein, putative CDS 0,002702081 PVP01_1425100 FAD-dependent monooxygenase, putative CDS 4,02571E-05 PVP01_1425200 importin beta, putative CDS 0,000628758 PVP01_1425800 conserved Plasmodium protein, unknown function CDS 1,53291E-23 PVP01_1428600 conserved Plasmodium protein, unknown function CDS 0,024793639 PVP01_1428900 conserved protein, unknown function CDS 1,4109E-11 PVP01_1429000 CCR4-associated factor 1, putative CDS 2,98408E-06 PVP01_1431000 conserved Plasmodium protein, unknown function CDS 2,94075E-05 PVP01_1437000 conserved Plasmodium protein, unknown function CDS 0,037929966 PVP01_1437200 triose or hexose phosphate/phosphatetranslocator, putative CDS 0,004744746 PVP01_1437400 arginyl-tRNA synthetase, putative CDS 0,005634453 PVP01_1438500 pre-mRNA-processing factor 17, putative CDS 2,70641E-05 PVP01_1438700 cell cycle associated protein, putative CDS 0,003813091 PVP01_1441500 DNA gyrase subunit A, putative CDS 0,034421264 PVP01_1442900 conserved Plasmodium protein, unknown function CDS 0,036105053 PVP01_1443700 small subunit rRNA processing factor, putative CDS 0,029512888 PVP01_1444100 conserved Plasmodium protein, unknown function CDS 0,001046432 PVP01_1444600 conserved Plasmodium protein, unknown function CDS 6,44993E-09 PVP01_1444700 RAP protein, putative CDS 2,2787E-07 PVP01_1447100 conserved Plasmodium protein, unknown function CDS 0,000104499 PVP01_1449200 conserved Plasmodium protein, unknown function CDS 0,017322709 PVP01_1450900 conserved Plasmodium protein, unknown function CDS 2,32823E-06 PVP01_1451200 elongation factor G, putative CDS 0,006913199

16 PVP01_1451300 conserved Plasmodium protein, unknown function CDS 6,50884E-05 PVP01_1451500 pentatricopeptide repeat domain-containingprotein, putative CDS 6,32526E-06 PVP01_1452800 CPW-WPC family protein CDS 2,82476E-07 PVP01_1452900 splicing factor 3B subunit 3, putative CDS 3,22813E-17 PVP01_1453400 CCR4-NOT transcription complex subunit 4,putative CDS 0,000174771 PVP01_1454000 pre-mRNA-splicing factor SYF1, putative CDS 0,000175556 PVP01_1454100 vesicle transport v-SNARE protein VTI1,putative CDS 0,001605632 PVP01_1456500 conserved Plasmodium protein, unknown function CDS 1,17867E-06 PVP01_1458300 conserved Plasmodium protein, unknown function CDS 0,04948217 PVP01_1458500 RNA-binding protein, putative CDS 0,001085349 PVP01_1459000 tetratricopeptide repeat protein, putative CDS 2,59861E-25 PVP01_1460100 syntaxin-like t-SNARE, putative CDS 0,000348985 PVP01_1462200 kinesin-13, putative CDS 1,36508E-07 PVP01_1462300 conserved Plasmodium protein, unknown function CDS 0,002270515 PVP01_1462600 conserved Plasmodium protein, unknown function CDS 0,000275035 PVP01_1463000 conserved Plasmodium protein, unknown function CDS 0,009207547 PVP01_1463600 conserved Plasmodium protein, unknown function CDS 2,61152E-11 PVP01_1463800 conserved Plasmodium protein, unknown function CDS 0,007871162 PVP01_1466900 hypothetical protein THO complex subunit 2, putative CDS 1,29245E-05 PVP01_1467900 DNA repair protein rhp16, putative CDS 0,026795586 PVP01_1468700 conserved Plasmodium protein, unknown function CDS 0,019416937

17 Supplementary Table 4. P. vivax-like genome-wide signatures of selection. The branch-site test of positive selection for orthologous genes as well as the P-value for this test are indicated. In orange are indicated genes with significant Dn/Ds ratios between P. vivax and P. vivax-like.

PVP01 Gene ID Gene product dN/dS p-value PVP01_0000040 Pvstp1 protein 0,043101978 PVP01_0105400 conserved Plasmodium protein, unknown function 0,035719627 PVP01_0106300 conserved Plasmodium protein, unknown function 0,000106214 PVP01_0109500 glutaredoxin-like protein 0,028972209 PVP01_0110000 lysophospholipase 0,000728955 PVP01_0111800 histone deacetylase complex subunit SAP18 0,032066503 PVP01_0113700 protein tyrosine phosphatase 0,000480899 PVP01_0113800 conserved Plasmodium protein, unknown function 0,024752739 PVP01_0114000 DnaJ protein 0,016536013 PVP01_0114500 AAA family ATPase 0,001836002 PVP01_0117900 periodic tryptophan protein 2 0,008467321 PVP01_0118300 conserved Plasmodium protein, unknown function 1,19123E-06 PVP01_0118500 sentrin-specific protease 2 0,018460996 PVP01_0119200 Plasmodium exported protein (PHIST), unknownfunction 0,02461943 PVP01_0119300 Plasmodium exported protein, unknown function 0,023365085 PVP01_0202300 Plasmodium exported protein, unknown function 0,017588021 PVP01_0207100 double-strand break repair protein MRE11 0,000484033 PVP01_0208300 conserved Plasmodium protein, unknown function 0,046703284 PVP01_0212700 vacuolar protein sorting-associated protein 53 0,00776122 PVP01_0214600 RNA-binding protein 0,014695746 PVP01_0304000 conserved Plasmodium protein, unknown function 1,5043E-07 PVP01_0307000 conserved Plasmodium protein, unknown function 1,69313E-09 PVP01_0308300 conserved Plasmodium protein, unknown function 0,008134942 PVP01_0310500 conserved Plasmodium protein, unknown function 0,012335919 PVP01_0310600 conserved Plasmodium protein, unknown function 0,000189783 PVP01_0310700 DEAD box ATP-dependent RNA helicase 0,001774624 PVP01_0313800 dynein heavy chain 5,02669E-08 PVP01_0316700 conserved Plasmodium protein, unknown function 0,000423001 PVP01_0317000 ATP-dependent RNA helicase DBP7 0,025551913 PVP01_0318000 ubiquitin C-terminal hydrolase 0,041323384 PVP01_0319100 conserved Plasmodium protein, unknown function 0,003982344 PVP01_0319900 type 2A phosphatase-associated protein 42 0,030218409 PVP01_0320600 kinesin-19 4,57618E-05 PVP01_0406800 conserved Plasmodium protein, unknown function 2,06979E-05 PVP01_0407800 conserved Plasmodium protein, unknown function 2,2473E-15 PVP01_0408500 conserved Plasmodium protein, unknown function 0,040103651 PVP01_0412200 SRR1-like protein 0,001021114 PVP01_0413700 ubiquinol-cytochrome-c reductase complexassembly factor 1 0,01689951

18 PVP01_0415900 6-cysteine protein transmission-blocking target antigen s230paralog 0,00679373 PVP01_0419100 DNA repair protein RAD2 2,01911E-06 PVP01_0420100 conserved Plasmodium protein, unknown function 0,005615187 PVP01_0420200 ubiE/COQ5 methyltransferase 0,007500571 PVP01_0420500 conserved Plasmodium protein, unknown function 1,35719E-06 PVP01_0507300 translation initiation factor IF-2 1,60945E-05 PVP01_0509400 conserved Plasmodium protein, unknown function 7,38967E-05 PVP01_0511900 conserved Plasmodium protein, unknown function 0,019377932 PVP01_0512500 protein transport protein SEC61 subunit beta 1,14903E-07 PVP01_0513800 conserved Plasmodium protein, unknown function 3,6405E-06 PVP01_0515000 conserved Plasmodium protein, unknown function 0,01425479 PVP01_0517900 phosphatase 0,010857846 PVP01_0518100 conserved Plasmodium protein, unknown function 0,000615228 PVP01_0521600 conserved Plasmodium protein, unknown function 0,007308736 PVP01_0522200 conserved Plasmodium protein, unknown function 0,000192955 PVP01_0526800 conserved Plasmodium protein, unknown function 6,21644E-07 PVP01_0527300 conserved Plasmodium protein, unknown function 0,003377832 PVP01_0601900 Plasmodium exported protein (PHIST), unknownfunction 0,003953012 PVP01_0603000 conserved Plasmodium protein, unknown function 0,030174413 PVP01_0605600 S-adenosyl-L-methionine-dependentmethyltransferase 0,020706636 PVP01_0607800 kelch protein 0,000918308 PVP01_0609800 RAP protein 0,002964236 PVP01_0610500 conserved Plasmodium protein, unknown function 0,002832823 PVP01_0611800 conserved Plasmodium protein, unknown function 0,009865615 PVP01_0613200 protoporphyrinogen oxidase 0,03054102 PVP01_0613800 merozoite TRAP-like protein 1,56644E-10 PVP01_0614800 conserved Plasmodium protein, unknown function 0,00200454 PVP01_0616400 conserved Plasmodium protein, unknown function 4,53447E-06 PVP01_0618000 RNA polymerase II-associated protein 1 0,004611687 PVP01_0618100 conserved Plasmodium protein, unknown function 0,000465467 PVP01_0620500 conserved Plasmodium protein, unknown function 0,005980721 PVP01_0621400 DNA polymerase zeta catalytic subunit 0,028104169 PVP01_0704000 WD repeat-containing protein 66 0,033218392 PVP01_0705900 ATP-dependent protease ATPase subunit ClpY 8,7825E-07 PVP01_0707400 conserved Plasmodium protein, unknown function 0,031113233 PVP01_0709900 conserved Plasmodium protein, unknown function 0,002833236 PVP01_0715500 N-glycosylase/DNA 0,039866622 PVP01_0718600 CS domain protein 0,008802095 PVP01_0725200 glutamine-dependent NAD(+) synthetase 0,04945475 PVP01_0727300 serine/threonine protein kinase 0,03800197 PVP01_0728600 conserved Plasmodium protein, unknown function 0,000290787 PVP01_0730400 PIH1 domain-containing protein 0,001245254 PVP01_0731400 conserved Plasmodium protein, unknown function 0,028475434 PVP01_0732000 conserved Plasmodium protein, unknown function 9,79301E-06 PVP01_0732200 gamma-tubulin complex component 0,008094809

19 PVP01_0801800 tryptophan-rich protein tryptophan-rich antigen 0,03160496 PVP01_0809800 conserved Plasmodium protein, unknown function 0,000585941 PVP01_0810000 conserved Plasmodium protein, unknown function 5,58014E-05 PVP01_0816600 conserved Plasmodium protein, unknown function 3,25428E-05 PVP01_0816800 Rh5 interacting protein 0,000284204 PVP01_0818400 WD repeat-containing protein 0,002179664 PVP01_0819200 conserved Plasmodium protein, unknown function 0,002369586 PVP01_0819700 nicotinamidase 9,31883E-09 PVP01_0819800 oocyst capsule protein 0,041706682 PVP01_0820800 kinesin-8 0,002243957 PVP01_0821600 conserved Plasmodium protein, unknown function 5,48289E-08 PVP01_0822000 stomatin-like protein 0,042079343 PVP01_0822600 kinesin-5 0,025322464 PVP01_0823700 conserved Plasmodium protein, unknown function 0,04871259 PVP01_0824500 zinc finger protein 0,000417371 PVP01_0825400 zinc finger protein 0,000214979 PVP01_0826400 conserved Plasmodium protein, unknown function 2,0907E-06 PVP01_0829800 TVN-junction protein 1, putative parasite-infected erythrocyte surface protein 3,18503E-08 PVP01_0833700 conserved Plasmodium protein, unknown function 0,017930077 PVP01_0835100 conserved Plasmodium protein, unknown function 0,001406091 PVP01_0905300 WD repeat-containing protein 0,001100889 PVP01_0906200 40S ribosomal protein S4 2,21948E-28 PVP01_0907200 conserved Plasmodium protein, unknown function 0,024189973 PVP01_0908600 transcription factor with AP2 domain(s) 2,27E-07 PVP01_0908700 mechanosensitive ion channel protein 0,000275425 PVP01_0908900 conserved Plasmodium protein, unknown function 0,033566377 PVP01_0913500 conserved Plasmodium protein, unknown function 0,001706478 PVP01_0913800 conserved Plasmodium protein, unknown function 0,000547474 PVP01_0914300 GTP-binding protein 0,022070381 PVP01_0918500 conserved Plasmodium protein, unknown function 0,007399711 PVP01_0920000 ubiquitin-protein ligase 4,94594E-05 PVP01_0921200 conserved Plasmodium protein, unknown function 5,84256E-05 PVP01_0921900 tyrosine kinase-like protein 1,93562E-07 PVP01_0923900 RING zinc finger protein 0,015728172 PVP01_0926000 DNA-directed RNA polymerase 0,011527657 PVP01_0931500 structural maintenance of chromosomes protein 1 0,004932664 PVP01_0932400 conserved Plasmodium protein, unknown function 0,004230207 PVP01_0932600 oxysterol-binding protein 8,631E-08 PVP01_0940500 conserved Plasmodium protein, unknown function 3,37181E-05 PVP01_0941200 myosin F 0,000109341 PVP01_1002400 conserved Plasmodium protein, unknown function 0,016339351 PVP01_1004500 conserved Plasmodium protein, unknown function 0,001215683 PVP01_1004800 conserved Plasmodium protein, unknown function 0,037625331 PVP01_1006400 conserved Plasmodium protein, unknown function 0,00122042 PVP01_1013500 conserved Plasmodium protein, unknown function 0,019144105

20 PVP01_1013700 conserved Plasmodium protein, unknown function 0,021436818 PVP01_1014400 carbon catabolite repressor protein 4 1,81665E-06 PVP01_1015400 ATP-dependent RNA helicase DDX23 0,016163663 PVP01_1018300 conserved Plasmodium protein, unknown function 0,010841563 PVP01_1018800 rhomboid protease ROM9 3,24549E-05 PVP01_1020700 conserved Plasmodium protein, unknown function 2,23842E-13 PVP01_1024700 conserved Plasmodium protein, unknown function 1,80045E-07 PVP01_1027300 GTPase-activating protein 0,000750067 PVP01_1028600 conserved Plasmodium protein, unknown function 0,000169408 PVP01_1104600 conserved Plasmodium protein, unknown function 1,07371E-06 PVP01_1109100 conserved Plasmodium protein, unknown function 0,006718679 PVP01_1111500 conserved Plasmodium protein, unknown function 0,038313813 PVP01_1113400 zinc finger protein 0,045651812 PVP01_1113900 patatin-like 0,023009073 PVP01_1115500 phosphatase 2A regulatory subunit-relatedprotein 0,007003068 PVP01_1117000 metacaspase 1 0,011872102 PVP01_1123900 poly(A) polymerase PAP 6,75476E-06 PVP01_1124500 sphingomyelin synthase 1 0,043178907 PVP01_1126800 conserved Plasmodium protein, unknown function 0,000799142 PVP01_1130700 conserved Plasmodium protein, unknown function 0,037307696 PVP01_1131400 conserved Plasmodium protein, unknown function 0,000846142 PVP01_1133000 conserved Plasmodium protein, unknown function 0,015774104 PVP01_1133700 ribonuclease 0,000126889 PVP01_1135800 rhoptry protein ROP14 3,3483E-08 PVP01_1139600 conserved Plasmodium protein, unknown function 0,022718079 PVP01_1139900 conserved Plasmodium protein, unknown function 0,005654011 PVP01_1140000 conserved Plasmodium protein, unknown function 2,68548E-09 PVP01_1141000 diphthine methyltransferase 0,003152979 PVP01_1141300 conserved Plasmodium protein, unknown function 0,012311504 PVP01_1141700 uroporphyrinogen III decarboxylase 0,009949265 PVP01_1141800 RING zinc finger protein 0,014559535 PVP01_1143100 DNA repair protein RAD50 2,5326E-05 PVP01_1143300 nucleoside diphosphate kinase 0,001418061 PVP01_1144600 conserved Plasmodium protein, unknown function 0,024504817 PVP01_1144800 transcription factor with AP2 domain(s) 0,015225267 PVP01_1145300 conserved Plasmodium protein, unknown function 1,53537E-08 PVP01_1147300 conserved Plasmodium protein, unknown function 3,89407E-08 PVP01_1203000 conserved Plasmodium protein, unknown function 2,27811E-08 PVP01_1205200 conserved Plasmodium protein, unknown function 0,049893332 PVP01_1205500 tyrosine kinase-like protein 0,023700654 PVP01_1206000 E1-E2 ATPase 0,000836538 PVP01_1206800 conserved Plasmodium protein, unknown function 0,010222662 PVP01_1208200 conserved Plasmodium protein, unknown function 0,037332951 PVP01_1212600 conserved Plasmodium protein, unknown function 0,00038034 PVP01_1213900 sodium-dependent phosphate transporter 0,001645264

21 PVP01_1217200 conserved Plasmodium protein, unknown function 0,012483161 PVP01_1221100 U3 small nucleolar RNA-associated protein 4 9,2772E-07 PVP01_1221500 ubiquitin-activating enzyme 0,022280813 PVP01_1222500 conserved Plasmodium protein, unknown function 0,000375666 PVP01_1224400 conserved Plasmodium protein, unknown function 0,000913212 PVP01_1225500 DNA-directed RNA polymerase III subunit RPC1 2,2573E-05 PVP01_1226200 conserved Plasmodium protein, unknown function 3,39924E-05 PVP01_1227500 conserved Plasmodium protein, unknown function 0,00109006 PVP01_1230600 conserved Plasmodium protein, unknown function 0,02917021 PVP01_1230800 vacuolar protein sorting-associated protein 52 0,0073114 PVP01_1233500 conserved Plasmodium protein, unknown function 0,018071115 PVP01_1237200 biotin carboxylase subunit of acetyl CoAcarboxylase 0,017082207 PVP01_1237500 pre-rRNA-processing protein PNO1 0,000675878 PVP01_1238200 aminophospholipid transporter 0,016910219 PVP01_1240000 conserved Plasmodium protein, unknown function 1,70264E-05 PVP01_1250400 conserved Plasmodium protein, unknown function 0,038229227 PVP01_1252700 serine/threonine protein kinase KIN 0,000329076 PVP01_1255100 ribosome biogenesis protein TSR1 0,014689395 PVP01_1256300 conserved Plasmodium protein, unknown function 0,000324496 PVP01_1259000 U3 small nucleolar RNA-associated protein 12 0,020217428 PVP01_1262600 conserved Plasmodium protein, unknown function 6,00311E-05 PVP01_1264700 methionine-tRNA ligase 0,015192467 PVP01_1264800 GTP-binding protein 0,000286298 PVP01_1265700 serine/threonine protein kinase 0,025476476 PVP01_1266600 conserved Plasmodium protein, unknown function 0,038174906 PVP01_1301100 cytochrome c oxidase assembly protein COX19 0,001431961 PVP01_1302500 signal recognition particle subunit SRP14 2,73949E-05 PVP01_1304600 zinc finger protein 0,038696951 PVP01_1305600 Tat binding protein 1(TBP-1)-interactingprotein 0,00189581 PVP01_1306100 conserved Plasmodium protein, unknown function 7,33732E-05 PVP01_1310800 lysine-specific histone demethylase 1 0,004664507 PVP01_1311300 peripheral plastid protein 1 0,018055811 PVP01_1311800 succinyl-CoA ligase 5,29459E-06 PVP01_1316100 conserved Plasmodium protein, unknown function 0,004456703 PVP01_1318200 conserved Plasmodium protein, unknown function 0,020719632 PVP01_1320000 rRNA (adenosine-2'-O-)-methyltransferase 0,000456681 PVP01_1325300 conserved Plasmodium protein, unknown function 4,83952E-05 PVP01_1325800 cyclophilin 0,017165022 PVP01_1325900 ankyrin 0,010583384 PVP01_1326300 conserved Plasmodium protein, unknown function 1,287E-08 PVP01_1326900 mitochondrial ribosomal protein L21 precursor 4,39251E-06 PVP01_1328700 tetratricopeptide repeat family protein 0,007536996 PVP01_1331800 conserved Plasmodium protein, unknown function 0,013369604 PVP01_1332100 lysine--tRNA ligase 0,047355968 PVP01_1334000 ATP-dependent protease 0,013179043

22 PVP01_1337500 plastid replication-repair enzyme 0,002064206 PVP01_1340200 conserved Plasmodium protein, unknown function 0,008070892 PVP01_1342700 RNA-binding protein 8A 2,10405E-05 PVP01_1343500 conserved Plasmodium protein, unknown function 0,00284739 PVP01_1346900 conserved Plasmodium protein, unknown function 0,002219273 PVP01_1402100 Plasmodium exported protein, unknown function 0,001446544 PVP01_1402600 conserved Plasmodium protein, unknown function 0,013953097 PVP01_1405300 conserved Plasmodium protein, unknown function 0,000178541 PVP01_1409600 conserved Plasmodium protein, unknown function 0,011402232 PVP01_1413100 conserved Plasmodium protein, unknown function 0,001921478 PVP01_1413400 translation initiation factor IF-2 0,024526602 PVP01_1415500 lipoate-protein ligase 1 0,003229364 PVP01_1417600 conserved Plasmodium protein, unknown function 0,021541193 PVP01_1422100 conserved Plasmodium protein, unknown function 0,000248696 PVP01_1432700 conserved Plasmodium protein, unknown function 7,77134E-21 PVP01_1436100 GTP-binding protein 0,021307019 PVP01_1437300 conserved Plasmodium protein, unknown function 0,018238922 PVP01_1439000 conserved Plasmodium protein, unknown function 0,009079041 PVP01_1441500 DNA gyrase subunit A 2,95354E-13 PVP01_1442700 histone chaperone ASF1 0,023723968 PVP01_1443300 isoleucine--tRNA ligase 2,23628E-07 PVP01_1443500 conserved Plasmodium protein, unknown function 3,17979E-08 PVP01_1444600 conserved Plasmodium protein, unknown function 1,3024E-11 PVP01_1444700 RAP protein 6,35481E-07 PVP01_1445700 cyclin 0,020648057 PVP01_1448400 vacuolar transporter chaperone 0,008012922 PVP01_1452900 splicing factor 3B subunit 3 0,007440022 PVP01_1453500 tetQ family GTPase 0,003159502 PVP01_1456900 acyl-CoA synthetase 0,043195311 PVP01_1462300 conserved Plasmodium protein, unknown function 0,001022546 PVP01_1462600 conserved Plasmodium protein, unknown function 0,000172307 PVP01_1464200 conserved Plasmodium protein, unknown function 3,71364E-07 PVP01_1464400 GPI mannosyltransferase 2 0,021150968 PVP01_1464700 conserved Plasmodium protein, unknown function 0,032063585 PVP01_1466700 leucine-rich repeat protein 0,002831341 PVP01_1467200 osmiophilic body protein 5,72628E-06 PVP01_1469800 tryptophan-rich protein tryptophan-rich antigen 0,007028669

23