CLUSTAL O(1.1.0) Multiple Sequence Alignment

Supplemental Figure 1

CLUSTAL O(1.1.0) multiple sequence alignment

human_PepT1|AAB61693.1 ------chimpanzee_PepT1|XP_522705.3 ------Rhesus_monkey_PepT1|NP_001028071.1 ------crab-eating_macaque_PepT1|AAQ56235.1 ------house_mouse_PepT1|NP_444309.2 ------Norway_rat_PepT1|BAA09318.1 ------dog_PepT1|NP_001003036.1 ------horse_PepT1|XP_001493109.3 ------MERAQHVTDADKYRHCVHVGSSERTPDK-G------RGQLVSRFRGDRRA pig_PepT1|AAO43094.1 ------cattle_PepT1|NP_001092848.1 ------sheep_PepT1|AAK14788.1 ------rabbit_PepT1|AAA17721.1 ------gray_short-tailed_opossum_PepT1|XP_001377037.2 MGAGLATLNGSASLGDVR------LWPSPRSEEKAGRNFAQLFFAKGMILQDFFYD--- platypus_PepT1|XP_001506250.2 ------chicken_PepT1|AAK39954.1 ------turkey_PepT1|AAO16604.1 ------western_clawed_frog_PepT1|XP_002935692.1 ------three-spined_stickleback_PepT1a| ------China_rockfish_PepT1a|ABV82968.1 ------Nile_tilapia_PepT1a| ------Japanese_medaka_PepT1a| ------mummichog_PepT1a|AEX92274.1 ------southern_platyfish_PepT1a| ------torafugu_PepT1a| ------Atlantic_cod_PepT1a| ------zebrafish_PepT1a|XP_001919914.3 ------Japanese_eel_PepT1a|BAM67012.1 ------common_carp_PepT1b|AEX13747.1 ------red_crucian_carp_PepT1b|AFI42054.1 ------red_crucian_x_common_carp_PepT1b|AFI42056.1 ------red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 ------grass_carp_PepT1b|AET36827.1 ------zebrafish_PepT1b|AAQ65244.1 ------Atlantic_cod_PepT1b|AAY17354.1 ------Atlantic_salmon_PepT1b|BAH24102.1 ------southern_platyfish_PepT1b| ------mummichog_PepT1b|AEX92273.1 ------spotted_green_pufferfish_PepT1b| ------torafugu_PepT1b| ------Japanese_medaka_PepT1b| ------Antarctic_icefish_PepT1b|AAO39705.2 ------three-spined_stickleback_PepT1b| ------European_seabass_PepT1b|ACI49693.2 ------white_grouper_PepT1b|AFP33141.1 ------yellow_perch_PepT1b|ACX49753.2 ------

human_PepT1|AAB61693.1 ------chimpanzee_PepT1|XP_522705.3 ------Rhesus_monkey_PepT1|NP_001028071.1 ------crab-eating_macaque_PepT1|AAQ56235.1 ------house_mouse_PepT1|NP_444309.2 ------Norway_rat_PepT1|BAA09318.1 ------dog_PepT1|NP_001003036.1 ------horse_PepT1|XP_001493109.3 GAAGMKGA------PE---MEKAVHR---R------GFAPTRLDSH-PFS-C---C--- pig_PepT1|AAO43094.1 ------cattle_PepT1|NP_001092848.1 ------sheep_PepT1|AAK14788.1 ------rabbit_PepT1|AAA17721.1 ------gray_short-tailed_opossum_PepT1|XP_001377037.2 -GAGIQTCLPFLPVPPSSHVSNSVKEILAAVL-----VLVGGDEEEI-HVS-C---L--- platypus_PepT1|XP_001506250.2 ------MAA---SKN-AAN-S---N--- chicken_PepT1|AAK39954.1 ------turkey_PepT1|AAO16604.1 ------western_clawed_frog_PepT1|XP_002935692.1 ------MDPSAPNRA-RADTC---PSTS three-spined_stickleback_PepT1a| ------MEANRYTEFFTC---TDNE China_rockfish_PepT1a|ABV82968.1 ------M---TDNE Nile_tilapia_PepT1a| ------M---TDNE Japanese_medaka_PepT1a| ------M---TDKE mummichog_PepT1a|AEX92274.1 ------southern_platyfish_PepT1a| ----MKH------SHSHLSGEKDK----VLSACGTNLKGARESEQQPHLNM---TEKD torafugu_PepT1a| ------MD Atlantic_cod_PepT1a| ----MKA------NYRDLARELSAIMHEQISPVEDGMKSVLPDSLHIFNAISGTPTGA zebrafish_PepT1a|XP_001919914.3 ------MPDS Japanese_eel_PepT1a|BAM67012.1 ------MT common_carp_PepT1b|AEX13747.1 ------MA red_crucian_carp_PepT1b|AFI42054.1 ------MAD red_crucian_x_common_carp_PepT1b|AFI42056.1 ------MA red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 ------MAA grass_carp_PepT1b|AET36827.1 ------M zebrafish_PepT1b|AAQ65244.1 ------M Atlantic_cod_PepT1b|AAY17354.1 ------ME Atlantic_salmon_PepT1b|BAH24102.1 ------MT southern_platyfish_PepT1b| ------MG mummichog_PepT1b|AEX92273.1 ------spotted_green_pufferfish_PepT1b| ------MA torafugu_PepT1b| ------M Japanese_medaka_PepT1b| ------MA Antarctic_icefish_PepT1b|AAO39705.2 ------ME three-spined_stickleback_PepT1b| ------MA European_seabass_PepT1b|ACI49693.2 ------white_grouper_PepT1b|AFP33141.1 ------MA yellow_perch_PepT1b|ACX49753.2 ------MA

1 %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% %%%%%% ######################################## human_PepT1|AAB61693.1 ------MGMSKSHSFFGYPLSIFFIVVNEFCERFSYYGMRAILILYFTNFISWDDNLSTA chimpanzee_PepT1|XP_522705.3 ------MGMSKSHSFFGYPLSIFFIVVNEFCERFSYYGMRAILILYFTNFISWDDNLSTA Rhesus_monkey_PepT1|NP_001028071.1 ------MGMSKSQGCFGYPLSIFFIVANEFCERFSYYGMRGILILYFTNFFSWDDNMSTA crab-eating_macaque_PepT1|AAQ56235.1 ------MGMSKSQGCFGYPLSIFFIVANEFCERFSYYGMRGILILYFTNFFSWDDNMSTA house_mouse_PepT1|NP_444309.2 ------MGMSKSRGCFGYPLSIFFIVVNEFCERFSYYGMRALLVLYFRNFLGWDDNLSTA Norway_rat_PepT1|BAA09318.1 ------MGMSKSRGCFGYPLSIFFIVVNEFCERFSYYGMRALLVLYFRNFLGWDDDLSTA dog_PepT1|NP_001003036.1 ------MGMSKSYGCFGYPLSIFFIVVNEFCERFSYYGMRALLILYFRRFIGWDDNLSTA horse_PepT1|XP_001493109.3 SSNRSSDRMSRSQSCFGYPLSIFFIVVNEFCERFSYYGMRALLILYFTLFIGWDDNLSTA pig_PepT1|AAO43094.1 ------MGMSVPQSCFGYPLSIFFIVVNEFCERFSYYGMRALLILYFRLFIGWNDNLSTA cattle_PepT1|NP_001092848.1 ------MGMSVPKSCFGYPLSIFFIVVNEFCERFSYYGMRALLILYFQRFLGWNDNLGTA sheep_PepT1|AAK14788.1 ------MGMSVPKSCFGYPLSIFFIVVNEFCERFSYYGMRALLILYFQRFLGWNDNLGTA rabbit_PepT1|AAA17721.1 ------MGMSKSLSCFGYPLSIFFIVVNEFCERFSYYGMRALLILYFRNFIGWDDNLSTV gray_short-tailed_opossum_PepT1|XP_001377037.2 -----DNGKKGTGSCLGYPISIFFIIVNEFCERFSYYGMRAILVLYFQRFLGWNDNLSTA platypus_PepT1|XP_001506250.2 AFQWAFLGMSKSLSCFGYPVSIFFIIINEFCERFSYYGMRAVLVLYFQRFLGWNDNLSTA chicken_PepT1|AAK39954.1 MAAKSKSKGRSVPNCFGYPLSIFFIVINEFCERFSYYGMRAVLVLYFKYFLRWDDNFSTA turkey_PepT1|AAO16604.1 MAAKSKSKGSSVPNCFGYPLSIFFIVINEFCERFSYYGMRAVLVLYFKYFLRWDDNLSTA western_clawed_frog_PepT1|XP_002935692.1 SALIQRRGEKKQPGCFGYPLSIFFIVINEFCERFSYYGMRAVLVLYFKYFLHWDDNLATV three-spined_stickleback_PepT1a| DPKKQKGGKGTSKVLFGYPLSIFFIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDLATS China_rockfish_PepT1a|ABV82968.1 DPKKGKDNRGTGTLVCGYPLSIFFIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDLATS Nile_tilapia_PepT1a| DPKKQGKGNGKSKDVCGYPLSIFFIVVNEFCERFSYYGMRAVLVLYFKYFLQWDEDLATS Japanese_medaka_PepT1a| DLKKEKKGKGKSKVVCGYPISIFFIVVNEFCERFSYYGMRAVLVLYFKYFLQWDDDLATS mummichog_PepT1a|AEX92274.1 -----MNSKKRRVTGCGYPISIFFIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDLATS southern_platyfish_PepT1a| DLKKESKGRGKCKEVFGYPISIFFIIVNEFCERFSYYGMRAVLVLYFKYFLRWDDDLAIS torafugu_PepT1a| EDHKKEKKRGTDKVVCGYPLSIFFIVVNEFCERFSYYGMRAVLVLYFRYFLLWGDDLATS Atlantic_cod_PepT1a| TIQGVPCTSSVSIVICGYPLSIFFIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDLATS zebrafish_PepT1a|XP_001919914.3 KMDETKKKKKKTAECCGYPISIFFIVVNEFCERFSYYGMRAVLVLYFRYFLLWDDDLATS Japanese_eel_PepT1a|BAM67012.1 DLEKREKKKPKSKVVCGYPISIFFIVVNEFCERFSYYGMRAVLVLYFRYFLRWDDDTATS common_carp_PepT1b|AEX13747.1 DEERNTKKAKNRPSCLGYPVSIFFIVVNEFCERFSYYGMKAVLVLYFKYFIGWDNDLSTT red_crucian_carp_PepT1b|AFI42054.1 NEERKTKKTKNRPSCLGYPVSIFFIVVNEFCERFSYYGMKAVLVLYFKYFIGWDNDLSTT red_crucian_x_common_carp_PepT1b|AFI42056.1 NEEKNTKKAKNRPSCLGYPVSIFFIVVNEFCERFSYYGMKAVLVLYFKYFIGWDNDLSTT red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 NEERKTKKTKNRPSCLGYPVSIFFIVVNEFCERFSYYGMKAVLVLYFKYFIGWDNDLSTT grass_carp_PepT1b|AET36827.1 ANKEGKNAREQGPSCLGYPVSIFFIVVNEFCERFSYYGMKAVLALYFKYFIGWDNDLSTT zebrafish_PepT1b|AAQ65244.1 ADKEGHKQKKERASCFGYPVSIFFIVVNEFCERFSYYGMKAVLVLYFKYFIGWDDDLSTT Atlantic_cod_PepT1b|AAY17354.1 DREN-GKKPKKSVTVCGYPLSIFFIVVDEFCERFSYYGMKAVLVLYFRYFLRWDDDLAIT Atlantic_salmon_PepT1b|BAH24102.1 DI--DVKKSKRKVDVCGYPLSIFFIVVNEFCERFSYYGMRAVLVLYFRYFLKWDDDLSTS southern_platyfish_PepT1b| DK-EKKTGKKKSVTIFGYPLSIFFIVVNEFCERFSYYGMRAVLVLYFKYFLKWDDDFSTT mummichog_PepT1b|AEX92273.1 -----MKSKKRSVTVCGYPLSIFFIVVNEFCERFSYYGMRAVLVLYFKYFLKWDDDFSTT spotted_green_pufferfish_PepT1b| DK---EKKKSKSKTVLDYPISIFFIVVNEFCERFSYYGMRTVLVLYLNNFLNWDEDFATT torafugu_PepT1b| DK---ETKKPKSKTLLGYPISIFFIVVNEFCERFSYYGMRTVLVLYLNYFLNFDDDFATT Japanese_medaka_PepT1b| DKEEHKKPKKKSPKVCGYPISIFFIVINEFCERFSYYGMRAVLVLYFKYFLRWDDDFATT Antarctic_icefish_PepT1b|AAO39705.2 DNDETKKPTQKTAVICGYPISIFFIVVNEFCERFSYYGMRAVLVLYFKYFLKWDDDFSTT three-spined_stickleback_PepT1b| AKDEGKDPKKKSATVCGFPISIFFIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDFATT European_seabass_PepT1b|ACI49693.2 ---MADGKKSKSATACGYPISIFFIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDFATT white_grouper_PepT1b|AFP33141.1 DTDEMRKPKKKSATIFGFPISIFFIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDFATT yellow_perch_PepT1b|ACX49753.2 DK-DIKKSKKKNATVCGYPLSFFFIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDFATT :*:*:***: :***********: :* **: *: : :: .

2 3 %%%%%%%%%%%%%%%%%%%%%%% %%%%%%%%%%%%%%%%%%%%% ###################### ######################## human_PepT1|AAB61693.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVTSVSSINDLTDHNHDGT chimpanzee_PepT1|XP_522705.3 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVISVSSINDLTDHNHDGT Rhesus_monkey_PepT1|NP_001028071.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVISVSSINDLTDHNHDGT crab-eating_macaque_PepT1|AAQ56235.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVISVSSINDLTDHNHDGT house_mouse_PepT1|NP_444309.2 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVISVSSINDLTDHDHNGS Norway_rat_PepT1|BAA09318.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVISVSSINDLTDHDHDGS dog_PepT1|NP_001003036.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVTAVSSINDLTDYNKDGT horse_PepT1|XP_001493109.3 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQVVLAVSSINDLTDGNRDGT pig_PepT1|AAO43094.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQVVMAVSSINDLTDFDHNGT cattle_PepT1|NP_001092848.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQVVIAVSSINDLTDFNHDGT sheep_PepT1|AAK14788.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQVVIAVSSINDLTDFNHDGT rabbit_PepT1|AAA17721.1 IYHTFVALCYLTPILGALIADAWLGKFKTIVWLSIVYTIGQAVTSLSSVNELTDNNHDGT gray_short-tailed_opossum_PepT1|XP_001377037.2 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTLGQAVTAISSINDLSDNNHDGN platypus_PepT1|XP_001506250.2 IYHTFIALCYLTPILGALIADSWLGKFKTIIYLSIVYTIGQAVTAISSINDLTDSDHDGT chicken_PepT1|AAK39954.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVMAVSSINDMTDQNRDGN turkey_PepT1|AAO16604.1 IYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVMAISSINDMTDQNRDGN western_clawed_frog_PepT1|XP_002935692.1 IYHTFVAICYLTPILGAIIADSWLGKFKTIVYLSIVYTVGQVVMAVSAIHDLTDGNRDGT three-spined_stickleback_PepT1a| IYHVFVALCYLTPILGAIVADSWLGKFKTIIYLSIVYAIGQVTMAVSAIHDITDTDRDGT China_rockfish_PepT1a|ABV82968.1 IYHVFVALCYLTPILGAIVADSWLGKFKTIIYLSIVYAIGQVAMAVSAVHDITDADRDGS Nile_tilapia_PepT1a| IYHTFVALCYLTPILGAIVADSWLGKFKTIIYLSIVYTIGQVAMAVSAVHDITDSNRDGT Japanese_medaka_PepT1a| IYHTFVALCYLTPILGAIVADSWLGKFKTIIYLSIVYAIGQVAMAVSAIHDITDSDRDGT mummichog_PepT1a|AEX92274.1 FYHTFVAFCYLTPILGAIVADSWLGKFKTIIYLSIVYAIGQVAMAVSAIHDITDSNRDGT southern_platyfish_PepT1a| IYHTFVAFCYLTPILGAIIADSWLGKFNTIIYLSIVYAIGQVAMAVSAIHDITDSDRDGS torafugu_PepT1a| IYHTFVALCYLTPILGAIVADSWLGKYKTIIYLSIVYAIGQVAMAVSAIHDITDTNHDGK Atlantic_cod_PepT1a| IYHAFVALCYLTPILGAIVADSWLGKFKTIIYLSIVYALGQVVMAISAIHDLTDYDWNGT zebrafish_PepT1a|XP_001919914.3 IYHAFVALCYLTPILGAIIADSWLGKFKTIIYLSIVYAVGQVVMAVSTIHDITDANRDGT Japanese_eel_PepT1a|BAM67012.1 IYHTFVALCYLTPIMGAIVADSWLGKFKTIVYLSIVYTIGQAVLAISAIHDITDKDQDGT common_carp_PepT1b|AEX13747.1 IYHTFVALCYLTPILGAIIADSWLGKFKTIVYLSIVYTIGQVIMAISAIHDITDTNRDGT red_crucian_carp_PepT1b|AFI42054.1 IYHTFVALCYLTPILGAIIADSWLGKFKTIVYLSIVYTIGQVIMAISAIHDITDTDKDGT red_crucian_x_common_carp_PepT1b|AFI42056.1 IYHTFVALCYLTPILGAMGANSWLGKFKTIVNLSIVYTIGQVIMAIRAIHDITDTNRDGT red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 IYHTFVALCYLTPILGAIIADSWLGKFKTIVYLSIVYTIGQVIMAISAIHDITDTNKDGT grass_carp_PepT1b|AET36827.1 IYHTFVALCYLTPIMGAIIADSWLGKFKTIVYLSIVYTIGQVIMAVSSIHDITDFNKDGV zebrafish_PepT1b|AAQ65244.1 IYHTFVALCYLTPIMGAIIADSWLGKFKTIVYLSIVYTIGQVIMAISAIHDITDANRDGK Atlantic_cod_PepT1b|AAY17354.1 IYHTFVALCYLTPILGAIVADSWLGKFKTIVYLSIVYTLGQVVMAISAIHDITDANKDGT Atlantic_salmon_PepT1b|BAH24102.1 IYHTFIALCYLTPILGAIVADSWLGKFKTIVYLSIVYTVGQVVMAVSAIHDITDTDRDGT southern_platyfish_PepT1b| IYHTFVALCYLSPILGAIIADSWLGKFKTIVYLSIVYTAGQVIMAVGAINDITDGNKDGT mummichog_PepT1b|AEX92273.1 IYHTFVALCYLSPILGAIVADSWLGKFKTIVYLSVVYAAGQVVMAVSAIHDITDGNKDGT spotted_green_pufferfish_PepT1b| IYHTFVALCYLTPILGAIVADSWLGKYKTIVYLSIVYAVGQVVLAVSAIHDITDTNRDGT torafugu_PepT1b| IYHTFVALCYLTPILGAIIADSWLGKYKTIVYLSIVYTVGQVVLAVSAIHDITDANRDGI Japanese_medaka_PepT1b| IYHTFVALCYLTPILGAIIADSWLGKFKTIVYLSIVYTLGQVVLAISAIHDITDTNKDGT Antarctic_icefish_PepT1b|AAO39705.2 IYHTFVALCYLTPILGAIVADSWLGKFKTIVYLSIVYMLGQVVMAISAIHDLTDANMDGT three-spined_stickleback_PepT1b| IYHTFVALCYLTPIMGAIVADSWLGKFKTIVYLSIVYTVGQVVLAVSAIHDITDTNRDGT European_seabass_PepT1b|ACI49693.2 IYHTFVALCYLTPILGAIVADSWLGKFKTIVYLSIVYTLGQIVMAISAIHDITDSNKDGI white_grouper_PepT1b|AFP33141.1 IYHTFVALCYLTPILGAIVADSWLGKFKTIVYLSIVYALGQVVLAVSAIHDITDANKDGT yellow_perch_PepT1b|ACX49753.2 IYHTFVALCYLTPILGAIVADSWLGKFKTIVYLSIVYTLGQVVMAISAIRDMTDGNKDGT :**.*:*:***:**:**: *::****::**: **:** ** :: ::.:::* : :* Supplemental Figure 1

4 5 %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% %%%%%%%%%%%%%%%%%%%%% ############################### #################### human_PepT1|AAB61693.1 PDSLPVHVVLSLIGLALIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS chimpanzee_PepT1|XP_522705.3 PDSLPVHVVLSMIGLALIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS Rhesus_monkey_PepT1|NP_001028071.1 PDSLPAHVALSMIGLALIALGTGGIKPCVSAFGGDQFEEGQEKRRNRFFSMFYLAINAGS crab-eating_macaque_PepT1|AAQ56235.1 PDSLPVHVALSMIGLALIALGTGGIKPCVSAFGGDQFEEGQEKRRNRFFSMFYLAINAGS house_mouse_PepT1|NP_444309.2 PDSLPVHVALSMVGLALIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINGGS Norway_rat_PepT1|BAA09318.1 PNNLPLHVALSMIGLALIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS dog_PepT1|NP_001003036.1 PDNLSVHVALSMIGLALIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS horse_PepT1|XP_001493109.3 PDSLPVHVALSMIGLALIAFGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS pig_PepT1|AAO43094.1 PNSMSVHVALSMIGLALIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS cattle_PepT1|NP_001092848.1 PDSISVHVALSMIGLVLIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS sheep_PepT1|AAK14788.1 PNNISVHVALSMIGLVLIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS rabbit_PepT1|AAA17721.1 PDSLPVHVAVCMIGLLLIALGTGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLAINAGS gray_short-tailed_opossum_PepT1|XP_001377037.2 PDNIALHVSLSMIGLALIALGTGGIKPCVSAFGGDQFEEHQEKQRNRFFSIFYLAINAGS platypus_PepT1|XP_001506250.2 PNVMSLHVALSMIGLALIALGTGGIKPCVSAFGGDQFEESQEKQRNRFFSIFYLAINAGS chicken_PepT1|AAK39954.1 PDNIAVHIALSMTGLILIALGTGGIKPCVSAFGGDQFEEHQEKQRSRFFSIFYLSINAGS turkey_PepT1|AAO16604.1 PDNIAVHIALSVTGLILIALGTGGIKPCVSAFGGDQFEEHQEKQRSRFFSIFYLSINAGS western_clawed_frog_PepT1|XP_002935692.1 PDTLEVHVALSVIGLLLIALGTGGIKPCVAAFGGDQFEENQDKQRSQFFSIFYLSINAGS three-spined_stickleback_PepT1a| PNNMTVHVVLSMLGLLLIALGTGGIKPCVAAFGGDQFSDHQEKQRRTFFSVFYLCINGGS China_rockfish_PepT1a|ABV82968.1 PDDMTFHVVLSMVGLFLIALGTGGIKPCVAAFGGDQFADHQEKQRRTFFSVFYLCINGGS Nile_tilapia_PepT1a| PDNMTFHVVLSMVGLFLIALGTGGIKPCVAAFGGDQFSEHQDKQRRTFFSVFYLCINGGS Japanese_medaka_PepT1a| PNNMTFHVVLSMVGLFLIALGTGGIKPCVAAFGGDQFDDHQEKQRRTFFSVFYLCINGGS mummichog_PepT1a|AEX92274.1 PDNLTFHVALSMVGLLLIALGTGGIKPCVAAFGGDQFGDTQEKQRRTFFSVFYLCINGGS southern_platyfish_PepT1a| PDNLTFHIVLSMVGLLLIALGTGGIKPCVAAFGGDQFGEHQDKQRRTFFSVFYLCINGGS torafugu_PepT1a| PDNMTFHVVLAMVGLFLIALGTGGIKPCVAAFGGDQFTDKQEKQRSTFFSVFYLCINGGS Atlantic_cod_PepT1a| PDNMTLHVALSMVGLVLIALGTGGIKPCVAAFGGDQFQDHQERQRSTFFSVFYLCINAGS zebrafish_PepT1a|XP_001919914.3 PDNFTLHIALSMLGLVLIALGTGGIKPCVAAFGGDQFQEHQSRQLNTFFSVFYLCINAGS Japanese_eel_PepT1a|BAM67012.1 PNNMTFHVALSMTGLILIALGTGGIKPCVAAFGGDQFSDEQEKQRSTFFSIFYLSINAGS common_carp_PepT1b|AEX13747.1 PDNMTFHTAMSMLGLILIALGTGGIKPCVAAFGGDQFEEHQEKQRSTFFSIFYLSINAGS red_crucian_carp_PepT1b|AFI42054.1 PDNMTFHTAMSMLGLILIALGTGGIKPCVAAFGGDQFEEHQEEQRSTFFSIFYLSINAGS red_crucian_x_common_carp_PepT1b|AFI42056.1 PDNMTFHTAMSMLGLILIALGTGGIKPCVAAFGGDQFEQHQEKQRNTFFSIFYLSINAGS red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 PDNMTFHTAMSMLGLILIALGTGGIKPCVAAFGGDQFEEHQEKQRSTFFSIFYLSINAGS grass_carp_PepT1b|AET36827.1 PDNMTLHIALSTLGLILIALGTGGIKPCVAAFGGDQFEEHQEKQRSTFFSIFYLSINAGS zebrafish_PepT1b|AAQ65244.1 PDNKTLHISLSMLGLILIALGTGGIKPCVAAFGGDQFEDHQEKQRSTFFSIFYLSINAGS Atlantic_cod_PepT1b|AAY17354.1 PDNMTFHVALSMVGLILIALGTGGIKPCVAAFGGDQFNEHQEKQRSTFFSIFYLSINAGS Atlantic_salmon_PepT1b|BAH24102.1 PDNMTFHVAMSMVGLFLIALGTGGIKPCVAAFGGDQFEEHQEKQRSTFFSIFYLSINAGS southern_platyfish_PepT1b| PDNMTFHIALSMVGLLLIALGTGGIKPCVAAFGGDQFNEDQEKQRSTFFSIFYLSINAGS mummichog_PepT1b|AEX92273.1 PDNMALHIALSMVGLLLIALGTGGIKPCVAAFGGDQFSEDQEKQRSTFFSIFYLSINAGS spotted_green_pufferfish_PepT1b| PDNMTFHVALSMVGLVLIALGTGGIKPCVAAFGGDQFEDHQEKQRGTFFSIFYISINAGS torafugu_PepT1b| PDNMTFHIALSMLGLILIALGTGGIKPCVAAFGGDQFEEHQDKQRSTFFSIFYLSINAGS Japanese_medaka_PepT1b| PDNMTFHVALSMVGLLLIALGTGGIKPCVAAFGGDQFEDHQEKQRGTFFSIFYLSINAGS Antarctic_icefish_PepT1b|AAO39705.2 PDNMTLHVALSMVGLILIALGTGGIKPCVAAFGGDQFLDHQEKQRSTFFSIFYLSINAGS three-spined_stickleback_PepT1b| PDNMTLHIVLSMLGLALIAVGTGGIKPCVSAFGGDQFQDHQEKQRGTFFSIFYLSINAGS European_seabass_PepT1b|ACI49693.2 PDNMTFHVALSMVGLILIALGTGGIKPCVAAFGGDQFEDHQEKQRSTFFSIFYLSINAGS white_grouper_PepT1b|AFP33141.1 PDNMTFHIALSMVGLILIALGTGGIKPCVAAFGGDQFDDDQEKQRSTFFSIFYLSINAGS yellow_perch_PepT1b|ACX49753.2 PDNMSIHVALSMVGLLLIALGTGGIKPCVAAFGGDQFQDHQEKQRSTFFSIFYLSINAGS *: * :. ** ***.*********:******* : *..: ***:**:.**.**

6 %%%%%%%%%%%%%% %%%%%%%%%%%%%%%%%%%%%%%%% ############# ########################### human_PepT1|AAB61693.1 LLSTIITPMLRVQQCGIHSKQACYPLAFGVPAALMAVALIVFVLGSGMYKKFKPQGNIMG chimpanzee_PepT1|XP_522705.3 LLSTIITPMLRVQQCGIHSKQACYPLAFGVPAALMAVALIVFVLGSGMYKKFKPQGNIMG Rhesus_monkey_PepT1|NP_001028071.1 LLSTIITPMLRVQQCGIHSKQACYPLAFGVPAALMAVALIVFILGSGMYKKFQPQGNIMG crab-eating_macaque_PepT1|AAQ56235.1 LLSTIITPMLRVQQCGIHSKQACYPLAFGVPAALMAVALIVFILGSGMYKKFQPQGNIMG house_mouse_PepT1|NP_444309.2 LLSTIITPILRVQQCGIHSQQACYPLAFGVPAALMAVALIVFVLGSGMYKKFQPQGNIMG Norway_rat_PepT1|BAA09318.1 LLSTIITPILRVQQCGIHSQQACYPLAFGVPAALMAVALIVFVLGSGMYKKFQPQGNIMG dog_PepT1|NP_001003036.1 LISTIVTPMLRVHECGIYSQKACYPLAFGVPAALMAVSLIVFVIGSGMYKKFQPQGNVMG horse_PepT1|XP_001493109.3 LLSTIITPILRVQQCGIHSKQACYPLAFGVPAALMAVSLIVFVIGSRMYKKFQPQGNIMA pig_PepT1|AAO43094.1 LLSTIITPMLRVQQCGIHSTQACYPLAFGVPAALMAVSLIVFVMGSRMYKKLKPQGNVMA cattle_PepT1|NP_001092848.1 LLSTIITPMLRVQVCGIHSKQACYPLAFGVPAALMAVSLIVFVIGSGMYKKVQPQGNIMS sheep_PepT1|AAK14788.1 LLSTIITPMLRVQVCGIHSKQACYPLAFGVPAALMAVSLIVFVIGSGMYKKVQPQGNIMS rabbit_PepT1|AAA17721.1 LLSTIITPMVRVQQCGIHVKQACYPLAFGIPAILMAVSLIVFIIGSGMYKKFKPQGNILS gray_short-tailed_opossum_PepT1|XP_001377037.2 LLSTIITPMLRVQQCGIHSKQACYPLAFGVPAALMAVSLIVFLIGSRMYKKVQPQGNVMA platypus_PepT1|XP_001506250.2 LLSTIITPMLRVQECGIHSKQSCYPLAFGVPAALMAIALVVFILGSGMYKKVQPQGNIMA chicken_PepT1|AAK39954.1 LISTIITPILRAQECGIHSRQQCYPLAFGVPAALMAVSLVVFIAGSGMYKKVQPQGNIMV turkey_PepT1|AAO16604.1 LISTVITPILRAQECGIHSRQQCYPLAFGVPAALMAVSLIVFIAGSGMYKKVQPQGNIMV western_clawed_frog_PepT1|XP_002935692.1 LLSTIITPILRGQECGIHSQQKCYPLAFGVPAALMVVALVVFIVGSSMYKKVSPQGNIIV three-spined_stickleback_PepT1a| LLSTIITPILRAQDCGIYSQQKCYSLAFGVPAALMLVALVVFIAGNGMYYKAEPQGNIML China_rockfish_PepT1a|ABV82968.1 LLSTIITPILRAQECGIYTKQKCYSLAFGVPAALMVVALVVFIVGSGMYYKAEPQGNIML Nile_tilapia_PepT1a| LLSTIITPILRGQECGIYSQQKCYSLAFGVPAALMVVALVVFIVGSGMYYKAEPEGNIML Japanese_medaka_PepT1a| LLSTIITPILRGQTCGIYSQQKCYALAFGVPAALMVVSLVVFIVGSGMYYKAKPEGNIML mummichog_PepT1a|AEX92274.1 LLSTIITPILRAQECGIHSKSKCYSLAFGVPAALMVVALVVFIMGSGMYYKAKPEGNIML southern_platyfish_PepT1a| LLSTIITPILRAQNCGIHSKSKCYSLAFGVPAALMAVSLVVFIMGSGMYYKTKPEGNIML torafugu_PepT1a| LLSTIITPILRAQECGIHTKQECYPLAFGVPAALMVVALVVFIVGSPMYYKAKPQGNIML Atlantic_cod_PepT1a| LLSTIITPILRAQECGIHTQQKCYSLAFGVPAALMVVALVVFIAGSGMYHKAEPQGNILL zebrafish_PepT1a|XP_001919914.3 LLSTLITPVLRAQECGIHTQQQCYPLAFGVPAALMVVSLVVFIAGSGMYTKTAPEGNIMG Japanese_eel_PepT1a|BAM67012.1 LLSTLITPILRAQECGIHTHQKCYPLAFGVPAALMVVALVVFIVGSKMYIKAAPKGNIML common_carp_PepT1b|AEX13747.1 LLSTLITPILRAQECGIYSKQSCFPLAFGVPAALMVVALIVFIAGHNMYIMESPKGNILL red_crucian_carp_PepT1b|AFI42054.1 LLSTLITPILRAQECGIYSKQSCFPLAFGVPAALMVVALIVFIAGHGMYIMESPKGNILL red_crucian_x_common_carp_PepT1b|AFI42056.1 LLSTLITPILRAQECGIYSKQSCFPLAFGVPAALMVVALIVFIAGHNMYIMESPKGNILL red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 LLSTLITPILRAQECGIYSKQSCFPLAFGVPAALMVVALIVFIAGHNMYIMESPKGNILL grass_carp_PepT1b|AET36827.1 LLSTLITPILRSQECGIYSKQSCFPLAFGVPAALMVVALVVFIAGHSMYIMESPKGNILL zebrafish_PepT1b|AAQ65244.1 LLSTLITPILRSQECGIYAKQSCYPLAFGVPAALMVVALIVFVIGHKMYIMESPKGNILL Atlantic_cod_PepT1b|AAY17354.1 LLSTIITPILRAQECGIYSQQKCYPLAFGVPAALMVVALIVFIVGSRMYTKVAPKGNIML Atlantic_salmon_PepT1b|BAH24102.1 LLSTVITPILRGQECGIHSQQKCYPLAFGVPAALMVVALIVFIMGSGMYNKTAPKGNIML southern_platyfish_PepT1b| LLSTIITPILRAQKCGIHTQQQCYPLAFGVPAALMVVSLIVFIVGSGMYNKTAPSGNIMV mummichog_PepT1b|AEX92273.1 LLSTVITPILRAQKCGIHTKQQCYPLAFGVPAALMVVALIVFILGSSMYNKTAPSGNIMV spotted_green_pufferfish_PepT1b| LLSTIITPILKAQECGIYTHQQCYPLAFGVPAALMFVALVVFIVGSPMYTKTAPQGNIMV torafugu_PepT1b| LLSTLITPILKAQECGIHTHQQCYPLAFGVPAALMFVALAVFIVGSPLYTKTAPQGNIMV Japanese_medaka_PepT1b| LLSTIITPILRGQECGIHTQQQCYPLAFGVPAALMAVALIVFIVGSGMYHKTAPQGNIMV Antarctic_icefish_PepT1b|AAO39705.2 LLSTVITPILRAQECGINTKQSCYPLAFGVPAALMVVALVVFILGSRMYIKTPPQGNIMV three-spined_stickleback_PepT1b| LLSTIITPILRGQECGIYTKQKCYSLAFGVPAGLMVASLIVFIVGSGMYIKTPPQGNIMV European_seabass_PepT1b|ACI49693.2 LLSTVITPILRAQECGIHTQQKCYPLAFGVPAALMVVALIVFIVGSGMYNKTAPQGNIIV white_grouper_PepT1b|AFP33141.1 LLSTVITPILRAQECGIHTQQKCYPLAFGVPAALMVVALIVFIVGSGMYTKNAPQGNILV yellow_perch_PepT1b|ACX49753.2 LLSTIITPILRAQECGIHTQQKCYSLAFGVPAALMVVALIVFIAGSGMYTKTAPQGNILV *:**::**::: : *** . *: ****:** ** :* **: * :* *.**:: Supplemental Figure 1

7 %%%%%%%%%%%%% ###################### human_PepT1|AAB61693.1 KVAKCIGFAIKNRFRHRSKAFPKREHWLDWAKEKYDERLISQIKMVTRVMFLYIPLPMFW chimpanzee_PepT1|XP_522705.3 KVAKCIGFAIKNRFRHRSKAFPKREHWLDWAKEKYDERLISQIKMVTRVMFLYIPLPMFW Rhesus_monkey_PepT1|NP_001028071.1 KVAKCIHFAIKNRFRHRSKAFPKREHWLDWAKEKYDERLISQIKMVMRVMFLYIPLPMFW crab-eating_macaque_PepT1|AAQ56235.1 KVAKCIHFAIKNRFRHRSKAFPKREHWLDWAKEKYDERLISQIKMVMRVMFLYIPLPMFW house_mouse_PepT1|NP_444309.2 KVAKCIGFAIKNRFRHRSKAYPKREHWLDWAKEKYDERLISQIKMVTKVMFLYIPLPMFW Norway_rat_PepT1|BAA09318.1 KVAKCIRFAIKNRFRHRSKAFPKRNHWLDWAKEKYDERLISQIKIMTKVMFLYIPLPMFW dog_PepT1|NP_001003036.1 KVVKCIGFALKNRFRHRSKQFPKREHWLDWAKEKYDERLISQIKMVTKVMFLYIPLPMFW horse_PepT1|XP_001493109.3 KVAKCIGFAITNRIRHRSNKFPKREHWLDWAKEKYDERLISQIKMVTRVMFLYIPLPMFW pig_PepT1|AAO43094.1 KVVKCIGFAIKNRFRHRSKKFPKREHWLDWAKEKYDERLICQIKMVTRVMFLYIPLPMFW cattle_PepT1|NP_001092848.1 KVARCIGFAIKNRIRHRSKKFPKRQHWLDWASEKYDERLISQIKMVTRVMFLYIPLPMFW sheep_PepT1|AAK14788.1 KVARCIGFAIKNRISHRSKKFPKREHWLDWASEKYDERLISQIKMVTRVMFLYIPLPMFW rabbit_PepT1|AAA17721.1 KVVKCICFAIKNRFRHRSKQFPKRAHWLDWAKEKYDERLIAQIKMVTRVLFLYIPLPMFW gray_short-tailed_opossum_PepT1|XP_001377037.2 EVAKCIGFAIKNRFKHRSKEFPKREHWLDWAKEKYDERLIAQIKMVVKVMFLYIPLPMFW platypus_PepT1|XP_001506250.2 QVAGCITFAVKNRFNHRSKTFPKREHWLDWASEKYDERLITQTKMVLKVMFLYIPLPMFW chicken_PepT1|AAK39954.1 RVCKCIGFAIKNRFRHRSKEYPKREHWLDWASEKYDKRLIAQTKMVLKVLFLYIPLPMFW turkey_PepT1|AAO16604.1 QVCKCIGFAIKNRFRHRSKEYPKREHWLDWASEKYDKRLIAQTKMVLKVLFLYIPLPMFW western_clawed_frog_PepT1|XP_002935692.1 KVSKCIGFAIRNRYRNRSKSIPKREHWLDWAKEKYDERLIAQIKMVLKVLFLYIPLPMFW three-spined_stickleback_PepT1a| DVCKCIGFAIKNRYKHRSSQYPKRQHWMDWAEDKYAKLLIAQIKMVLRVLFLYIPLPMFW China_rockfish_PepT1a|ABV82968.1 DVCKCIGFAVKNRYRHRSEQHPKRKHWMDWE-EKYEKLLIAQIKMVLKVLFLYIPLPMFW Nile_tilapia_PepT1a| DVCKCIGFAIKNRYRHRSKQYPKRQHWMDWAEEKYDKLLIAQIKMVLKVLFLYIPLPMFW Japanese_medaka_PepT1a| SVCKCIGFAIKNRYRHRSKAYPKRKHWMDWAEEKYDRLLIAQIKMVLKVLFLYIPLPMFW mummichog_PepT1a|AEX92274.1 KVSKCIGFAIKNRYKHRSSQYPKREHWMDWAEEKYDKLLIAQIKISLRVLFLYIPLPMFW southern_platyfish_PepT1a| KVSKCIGFAIKNRYRHKSKQYPKREHWMDWAEEKYDKLLIAQIKIALRVLVLYIPLPMFW torafugu_PepT1a| KVCKCIGFAIKNRYRHRSSNYPKREHWMDWAEDKYEKLLIAQIKMVLRVLFLYMPLPMFW Atlantic_cod_PepT1a| DVCKCIGFAIKNRFRHRGKEFPKRTHWMDWADEKYEKLLIAQIKMVLKVLFLYIPLPMFW zebrafish_PepT1a|XP_001919914.3 SVCKCIWFALNNRFRHRSDIYPKREHWMDWAEEKYDKLLIAQIKMVLKVLFLYIPLPMFW Japanese_eel_PepT1a|BAM67012.1 EVSKCIGFAVKNRFRHRSDEYPKREHWMDWAEEKYERLLIAQVKMVLRVLFLYIPLPMFW common_carp_PepT1b|AEX13747.1 QVMKCIGFAIRNRFNHRSKQHPKREHWMDWAEEEYDKLLIAQVKMVLKVLFLYIPLPMFW red_crucian_carp_PepT1b|AFI42054.1 QVMNCIGFAVSNRFNHRGKQYPKREHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW red_crucian_x_common_carp_PepT1b|AFI42056.1 QVMKCIGFAIRNRFNHRSKQHPKREHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 QVMKCIGFAIRNRFNHRSKQHPKREHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW grass_carp_PepT1b|AET36827.1 RVMNCIIFALSNRFEHRGKQYPKREHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW zebrafish_PepT1b|AAQ65244.1 QVINCIGFALNNRFRHRGKQYPKREHWMDWAEEKYDKLLIAQVKMVVKVLFLYIPLPMFW Atlantic_cod_PepT1b|AAY17354.1 EVCKCIWYAVKNRFRNRSSSIPKREHWMDWADEKYEKLLIAQIKMVLKVLFLYIPLPMFW Atlantic_salmon_PepT1b|BAH24102.1 EVCKCIGFAVKNRFRHRSKKFPKREHWMDWADEKYDKLLVAQVKMVLKVMFLYIPLPMFW southern_platyfish_PepT1b| KVCKCIFFAIMNRFHNRSSQIPKREHWLDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW mummichog_PepT1b|AEX92273.1 KVCKCIFFAIKNRFRHRSSAYPKREHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW spotted_green_pufferfish_PepT1b| KFCKCVGFAIKNRFRHRSSQYPKRAHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW torafugu_PepT1b| KVCKCIGFAIKNRFRHRASHYPKRAHWMDWAEEKYDKLLIAQVKMVLKVLFLFIPLPMFW Japanese_medaka_PepT1b| KVTKCIGFAIKNRFRHRSSQYPKREHWMDWADEKYDKLLIAQVKMVLKVLFLYIPLPMFW Antarctic_icefish_PepT1b|AAO39705.2 KVCTCIGFAVKNRFRHRSSHYPKREHWMDWSDEKYDKLLIAQVKMVLKVLFLYIPLPMFW three-spined_stickleback_PepT1b| KFFTCIGFAIKNRFRHRTNEFPKRTHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW European_seabass_PepT1b|ACI49693.2 QVCKCIGFAIKNRFRHRAREHPCRTHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW white_grouper_PepT1b|AFP33141.1 KVCKCIGFAIKNRFRHRAPEYPKRTHWMDWAEEKYDKLLIAQVKMVLKVLFLYIPLPMFW yellow_perch_PepT1b|ACX49753.2 KVCKCIGFAIKNRFRHRGSEYPKRTHWMDWAEEKYSKLLIAQVKMVVRVLFLYIPLPMFW . *: :*: ** .: * * **:** ::* . *: * *: :*:.*::******

8 %%%%%%%%%%%%%%%% %%%%%%%%%%%%%%%%%%%%%%%%%%%% ################# ####################### human_PepT1|AAB61693.1 ALFDQQGSRWTLQATTMSGKIGALEIQPDQMQTVNAILIVIMVPIFDAVLYPLIAKCGFN chimpanzee_PepT1|XP_522705.3 ALFDQQGSRWTLQATTMSGKIGALEIQPDQMQTVNAILIVIMVPIFDAVLYPLIAKCGFN Rhesus_monkey_PepT1|NP_001028071.1 ALFDQQGSRWTLQAATMSGKIGALEIQPDQMQTVNAILIVIMVPIFDAVLYPLIAKCGLN crab-eating_macaque_PepT1|AAQ56235.1 ALFDQQGSRWTLQAATMSGKIGALEIQPDQMQTVNAILIVIMVPIFDAVLYPLIAKCGLN house_mouse_PepT1|NP_444309.2 ALFDQQGSRWTLQATTMNGKIGAIEIQPDQMQTVNAILIVIMVPIVDAVVYPLIAKCGFN Norway_rat_PepT1|BAA09318.1 ALFDQQGSRWTLQATTMTGKIGTIEIQPDQMQTVNAILIVIMVPIVDAVVYPLIAKCGFN dog_PepT1|NP_001003036.1 ALFDQQGSRWTLQATAMSGKIGLLEVQPDQMQTVNAILIVVMVPIMDAVVYPLIAKCGFN horse_PepT1|XP_001493109.3 ALFDQQGSRWTLQATTMNGQIGVIEIQPDQMQTVNAILIVIMVPIMDAVVYPLIAKCGLN pig_PepT1|AAO43094.1 ALFDQQGSRWTLQATTMNGQIGLLKIQPDQMQTVNAILIVIMVPIMDAVVYPLIAKCGLN cattle_PepT1|NP_001092848.1 ALFDQQGSRWTLQATTMSGKIGIIEIQPDQMQTVNAILIVIMVPIVDAVVYPLIAKCGLN sheep_PepT1|AAK14788.1 ALFDQQGSRWTLQATTMSGKIGIIEIQPDQMQTVNAILIVVMVPIVDAVVYPLIAKCGLN rabbit_PepT1|AAA17721.1 ALFDQQGSRWTLQATTMSGRIGILEIQPDQMQTVNTILIIILVPIMDAVVYPLIAKCGLN gray_short-tailed_opossum_PepT1|XP_001377037.2 ALFDQQGSRWTLQATTMNGNFGTIEIQPDQMQTVNAILIVIMVPIVDAVVYPLIAKCGFN platypus_PepT1|XP_001506250.2 ALFDQQGSRWTLQATTMNGKFGSIEIQPDQMQTVNAILIVVMVPVVDGVIYPLIAKCGFN chicken_PepT1|AAK39954.1 ALFDQQGSRWTLQATTMDGDFGAMQIQPDQMQTVNPILIIIMVPVVDAVIYPLIQKCKIN turkey_PepT1|AAO16604.1 ALFDQQGSRWTLQATTMDGDFGALQIQPDQMQTVNPILIIIMVPVVDAVIYPLIQKCKIN western_clawed_frog_PepT1|XP_002935692.1 ALFDQQGSRWTLQATTMDGNFGAIQIQPDQMQTVNPILIIVLVPIFDAAVYPLIRKCKLD three-spined_stickleback_PepT1a| TLFDQKGSRWTLQATNLNGNFGLLVIQPDQMQTVNPILILTLVPVMDSIIYPLIRKCGAN China_rockfish_PepT1a|ABV82968.1 TLFDQKGSRWTLQATAMDGDFGLLVIQPDQMQTVNPILILTLVPIMDSVIYPLIKKCGLN Nile_tilapia_PepT1a| TLFDQKGSRWTLQATTMNGYFGQLVIQPDQMQTFNPILILTLVPIMDSVIYPLIKKCGFN Japanese_medaka_PepT1a| TLFDQKGSRWTLQATTMDGNFGQLVIQPDQMQTFNPILILTLVPIMESVVYPLIKKCGFN mummichog_PepT1a|AEX92274.1 TLFDQKGSRWTLQATTMNGHFGSIVIQPDQMQTINPILILTLVPIMDSLIYPLIRKCGLN southern_platyfish_PepT1a| TLFDQKGSRWTLQATTMDGNFGSIVIQPDQMQTINPILILTLVPVMDSLVFPLIKKCGLN torafugu_PepT1a| TLFDQKGSRWTLQATTMNGDYGALVIQPDQMQTFNPILILTLVPIMDSLIYPLIKKCGLN Atlantic_cod_PepT1a| TLFDQKGSRWTFQATTMDGNFGLLVLQPDQMQTVNPILILTLVPIMDSVVYPLIRKCGLN zebrafish_PepT1a|XP_001919914.3 TLFDQKGSRWTLQATTMTGDFGGFVLQPDQMQTVNPILILTLVPIMDRIIFPLIKKCGLN Japanese_eel_PepT1a|BAM67012.1 ALFDQQGSRWTLQATTMDGNFGALIIQPDQMQTVNPILILVLVPIMDSAVYPLIKKCGLN common_carp_PepT1b|AEX13747.1 ALFDQQGSRWTLQATTMDGNFGAFIIQPDQMQIVNPILIVIMVPIMDSAVYPLIKKCGLN red_crucian_carp_PepT1b|AFI42054.1 ALFDQQGSRWTLQATTMDGNFGAFIIQPDQMQIVNPILIVIMVPIMDSVVYPLIKKCGLN red_crucian_x_common_carp_PepT1b|AFI42056.1 ALFDQQGSRWTLQATTMDGNFGAFIIQPDQMQIVNPILIVIMVPIMDSAVYPLIKKCGLN red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 ALFDQQGSRWTLQATTMDGNFGAFIIQPDQMQIVNPILIVIMVPIMDSAVYPLIKKCGLN grass_carp_PepT1b|AET36827.1 ALFDQQGSRWTIQATTMDGNFGAFIIQPDQMQIVNPILIVIMVPIMDSAVYPLIKMCRIN zebrafish_PepT1b|AAQ65244.1 ALFDQQGSRWTIQATTMDGNFGGFVIQPDQMQIVNPILIVIMVPIMDSAIYPLIKLCRIN Atlantic_cod_PepT1b|AAY17354.1 TLFDQQSSRWTLQATTMDGDFGLLVIQPDQMQTVNPILILGFVPIVDSVIYPLIAKCGLN Atlantic_salmon_PepT1b|BAH24102.1 TLFDQQGSRWTLQATTMDGNFGILTVQPDQMQTVNPILILALVPIMDSLVYPLIKKCHLN southern_platyfish_PepT1b| ALFDQQGSRWTLQATTMDGNFGLMVIQPDQMQTVNPILILIMVPVMDFIIYPLISKCKLN mummichog_PepT1b|AEX92273.1 ALFDQQGSRWTLRATTMDGNFGLMVIQPDQMQTVNPILILIMVPVVDFIIYPLISKCKLN spotted_green_pufferfish_PepT1b| ALFDQQGSRWTLQATTMDGKFGSLEIQPEHMQTVNPILILVLVPIMDTLIYPLISKCKLN torafugu_PepT1b| ALFDQQGSRWTLQATTMDGNFGSLEIQPEQMQIVNPILILILVPIMDSIVYPLINKCKLN Japanese_medaka_PepT1b| ALFDQQGSRWTLQATTMDGDFGALTIQPDQMQTVNPILILILVPIMDTLIYPLISKCKLN Antarctic_icefish_PepT1b|AAO39705.2 ALFDQQGSRWTLQATIMDGDFGFLTIQPDQMQTVNPILILIMVPIMDSAIYPLIAKCNLN three-spined_stickleback_PepT1b| ALYDQQGSRWTLQATNMDGDFGILTIQPDQMQTINAILILLLVPIVESVIYPLIAKCKIN European_seabass_PepT1b|ACI49693.2 ALFDQQGSRWTLQATTMDGDFGALIIQPDQMQTVNPILILVLVPIMDSLVYPLISKCKLN white_grouper_PepT1b|AFP33141.1 ALFDQQGSRWTLQATTMDGDFGLLIIQPDQMQTVNPILILVLVPIMDSLIYPLIAKCKLN yellow_perch_PepT1b|ACX49753.2 ALFDQQGSRWTLQATTMDGNFGILTIQPDQMQTVNPILILVFVPFVDSVIYPLIAKCKLN :*:**:.****::*: : * * : :**::** .* ***: :**..: ::*** * : Supplemental Figure 1

9 %%%%%%%%%%%%%%%%%%%%%%%% ########################### human_PepT1|AAB61693.1 FTSLKKMAVGMVLASMAFVVAAIVQVEIDKTLPVFPKGNEVQIKVLNIGNNTMNISLPGE chimpanzee_PepT1|XP_522705.3 FTSLKKMTVGMFLASMAFVVAAIVQVEIDKTLPVFPKGNEVQIKVLNIGNNTMNISLPGE Rhesus_monkey_PepT1|NP_001028071.1 FTSLKKMTVGMFLASLAFVVAAIVQVEIDKTLPVFPKGNEIQIKVLNIGNTTMNISLPGE crab-eating_macaque_PepT1|AAQ56235.1 FTSLKKMTVGMFLASLAFVVAAIVQVEIDKTLPVFPKGNEIQIKVLNIGNTTMNISLPGE house_mouse_PepT1|NP_444309.2 FTSLKKMTVGMFLASMAFVVAAIVQVEIDKTLPVFPGGNQVQIKVLNIGNNNMTVHFPGN Norway_rat_PepT1|BAA09318.1 FTSLKKMTVGMFLASMAFVVAAIVQVEIDKTLPVFPSGNQVQIKVLNIGNNDMAVYFPGK dog_PepT1|NP_001003036.1 FTSLKRMTVGMFLASMAFVMAAIVQLEIDKTLPVFPKQNEVQIKVLNIGNGAMNVSFPGA horse_PepT1|XP_001493109.3 FTSLKKMTVGMFLASMAFVAAAIVQVEIDKTLPVFPNGHEVQVKVLNIGNNSMNISFPGE pig_PepT1|AAO43094.1 FTSLRKMTVGMFLASMAFVAAAIVQVEIDKTLPVFPKGNEVQVKVLNIGNNSMSVSFPGT cattle_PepT1|NP_001092848.1 FTSLKKMTVGMFLASMAFVAAAIVQVEIDKTLPVFPKGNEVQIKVLNIGDSNMTVSFPGT sheep_PepT1|AAK14788.1 FTSLKKMTVGMFLASMAFVAAAIVQVDIDKTLPVFPKGNEVQIKVLNIGNNSMTVSFPGT rabbit_PepT1|AAA17721.1 FTSLKKMTIGMFLASMAFVAAAILQVEIDKTLPVFPKANEVQIKVLNVGSENMIISLPGQ gray_short-tailed_opossum_PepT1|XP_001377037.2 FTSLKKMTVGMFLASMAFVVAAIIQLQIDKTLPVFPKGNEIQVQVLNVGNENLTAYFPGS platypus_PepT1|XP_001506250.2 FTSLKKMTVGMFLASMAFVVAAIIQMQIDKTLPVFPTAQEFQVRVVNLGQESMNVIFPGK chicken_PepT1|AAK39954.1 FTPLRRITVGMFLAGLAFVAAALLQVQIDKTLPVFPAAGQAQIKIINLGDSNANVTFLPN turkey_PepT1|AAO16604.1 FTPLRKITVGMFLAGLAFIAAALVQVQIDKTLPVFPAAGQAQIRIINLGNSNANVTFLPD western_clawed_frog_PepT1|XP_002935692.1 FTPLKRMTVGMFLAAMAFVAAALVQIEIDKTLPTFPSSNEFQLKVINLGTKDLNVTYVAN three-spined_stickleback_PepT1a| FTPLKRMAVGMMMAAIAFVCAAVVQIEIDKTLPTFPSASQSQLKLLNMESNPVTVQLPGL China_rockfish_PepT1a|ABV82968.1 FTPLKRMTVGMMMAAIAFVCAALVQLQIDQTLPTFPSASQSQLKLLNMGSNQVTVTLPGN Nile_tilapia_PepT1a| FTPLKRMTVGMFLAAMAFVCAALVQVEIDKTLPVFPSASQSQLKLLNMGSSAVTVNLTGN Japanese_medaka_PepT1a| FTPLKRMTVGMFLAALAFVCAGVVQLQIDKTLPIFPSTSESQLKLLNMGNNQLEVHLPNN mummichog_PepT1a|AEX92274.1 FTPLKKMTVGMILAALAFVCAAMVQLQIDKTLPIFPSASQSQLKLLNMENNQLEVHLPNN southern_platyfish_PepT1a| FTPLKKMTVGMIVAALAFVCAAVIQLQIDKTLPVFPSASQSQLKFLNMGNTQITVQFQGN torafugu_PepT1a| FTPLKRMTVGMVLAAIAFICAALVQLEIDKTLPTFPSSSQTQIKLVNMNLNSVNVSLPGI Atlantic_cod_PepT1a| FTPLKRMTVGMFLAAMAFVAAALVQIEIDKTLPVFPSGVQSQLKTINLGRDPMTLTLSQH zebrafish_PepT1a|XP_001919914.3 FSPLKRMTVGMLFAATAFIAAALVQMEIDKTLPNFPSSSESQLKVVNMHSESLIVTVPSQ Japanese_eel_PepT1a|BAM67012.1 FTPLRRMTVGMLLAGLAFVAAALVQIEIDKTLPKFPSSSESQLKFLNLGSSQLEITAATN common_carp_PepT1b|AEX13747.1 FTPLRRMTVGMPLASLAFVAAALLQIQIDRTVPNFPSSSQTQVKFLNLENTPVPVVVEGQ red_crucian_carp_PepT1b|AFI42054.1 FTPLRRMTVGMVLAALAFVAAALLQIQIDQTVPDFPSNSQTQVKFLNLEETSVPVIVEGQ red_crucian_x_common_carp_PepT1b|AFI42056.1 FTPLRRMTVGMLLAALAFVAAALLQIQIDRTVPNFPSSSQTQVKFLNLENTPVPVVVEGQ red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 FTPLRRMTVGMLLAALAFVAAALLQIQIDRTVPNFPSSSQTQVKFLNLENTPVPVVVEGQ grass_carp_PepT1b|AET36827.1 FTPLRKMTVGMLLAALAFVAAALLQIQIDQTMPQFPSSSQTQVKFLNLEKTSLPVLVEGQ zebrafish_PepT1b|AAQ65244.1 FTPLRKMTVGMVLAALAFVAAALLQLQIDETMPKFPSTSQTQLKFLNVESTSLPVVVEGQ Atlantic_cod_PepT1b|AAY17354.1 FTPLKRMTVGMFMAALAFIAAALVQLQIDETLPVFPASNGGQIKVFNLAGATVDVSVGGQ Atlantic_salmon_PepT1b|BAH24102.1 FTPLKRMTVGMLIAALAFVAAALLQLQIDQTLPKLPQGVAGQVKFLNLNSAPLTLTIDGT southern_platyfish_PepT1b| FTPLRKITVGMFLAGLAFVAAALVQLQIDATLPDFPSSTEQQAKFINMVNRSIDITAGKY mummichog_PepT1b|AEX92273.1 FTPLRKMTGGMFLAALAFVAAALVQLQIDATLPTFPSSNEQQAKFINMVNRNLSIADGRE spotted_green_pufferfish_PepT1b| FSPLKRMTVGMLLASVAFVAAALVQLEIDKTLPDFPAGEESQVKFVNMLNEKINFTAGDQ torafugu_PepT1b| FSPVKRMTVGMFLAAMAFVAAALVQLQIDSTLPNFPKGQESQVKFINMLNTKIDFTAGNK Japanese_medaka_PepT1b| FTPLRRITVGMFFAAMAFVAAAVVQLQIDKTLPKFPSNSEMQVKFINAVNREVDITAGGH Antarctic_icefish_PepT1b|AAO39705.2 FSPLKRMTVGMLFAALAFVAAALVQLQIDQTMPIFPSSTESQVKYINMMSTPLDVRAGNN three-spined_stickleback_PepT1b| FTPLRRITVGMFFAALAFIAAALVEIQIERTLPKFPSSPEVQVKFINMGNKSLDLTAGTN European_seabass_PepT1b|ACI49693.2 FSPLKRMTVGMFLAALAFIAAALVQIQIDQTLPKFPSSTVGQAKFINMVNRALNINAGPN white_grouper_PepT1b|AFP33141.1 FTPLKRMTVGMFLAALAFICAALVQIQIDKTPPQFPSSTVGQAKFINMLDRSLDVKAGTN yellow_perch_PepT1b|ACX49753.2 FTPLKRMTVGMFLAALAFIAAALVQIQIDKTLPQFPSSTVGQAKFINMINRPLDVKAGTN *: ::::: ** .*. **: *.:::::*: * * :* * : .*

human_PepT1|AAB61693.1 MVTL--GPMSQTNAFMTFDVNKLTRINISSPGSP-VTAVTDDFKQGQRHTLLVWA---PN chimpanzee_PepT1|XP_522705.3 MVTL--GPMSQTNAFMTFDVNKLTSINISSPGSP-VTAVTDDFKQGQRHTLLVWA---PN Rhesus_monkey_PepT1|NP_001028071.1 MVTL--DSLSQTNAYMTFDVNKLTSINISSPGSP-VTAVTDDFKQGQRHTLLVWA---PN crab-eating_macaque_PepT1|AAQ56235.1 MVTL--DSLSQTNAYMTFDVNKLTSINISSPGSP-VTAVTDDFKQGQRHTLLVWA---PN house_mouse_PepT1|NP_444309.2 SVTL--AQMSQTDTFMTFDIDKLTSINISSSGSPGVTTVAHDFEQGHRHTLLVWN---PS Norway_rat_PepT1|BAA09318.1 NVTV--AQMSQTDTFMTFDVDQLTSINVSSPGSPGVTTVAHEFEPGHRHTLLVWG---PN dog_PepT1|NP_001003036.1 VVTV--SQMSQSDGFMTFDVDKLTSINISSTGSP-VIPVTYNFEQGHRHTLLVWA---PN horse_PepT1|XP_001493109.3 TMAV--NQMSQTGDFMTFDVDKL-SINISSTGSP-VTPVTHNFEQGHRHTILVWA---PN pig_PepT1|AAO43094.1 TVTL--DQMSQTHEFLTFDVNKLTSINISSAGSP-ATPVTYNFEQGHRHTLLVWG---PS cattle_PepT1|NP_001092848.1 TETY--NQMSQPKDFMTFNVDNL-SINISSTGSP-VTPVTHNFESGHRHTLLVWA---PS sheep_PepT1|AAK14788.1 TVTC--DQMSQTNGFLTFNVDNL-SINISSTGTP-VTPVTHNFESGHRHTLLVWA---PS rabbit_PepT1|AAA17721.1 TVTL--NQMSQTNEFMTFNEDTLTSINITSGSQ--VTMITPSLEAGQRHTLLVWA---PN gray_short-tailed_opossum_PepT1|XP_001377037.2 EHRN--VSVNESSGFLTLDFNSPPNINISFGQQP-PFQVPNDFERGYRHSILAWN---SS platypus_PepT1|XP_001506250.2 EAVA--LNLRDKTEFMKLDVNNVNYVVISTAST--IENHTIPFKEGQRQTLLLWS---PS chicken_PepT1|AAK39954.1 LQNVTVLP-MESTGYRMFESSQLKSVMVNFGSESRSE-NIDSISSNTH-TVTIKNAAAGI turkey_PepT1|AAO16604.1 LQNVTVLP-MESTNYRIFETSQLKSVIINFGSENRSE-SIDSTSSNTH-TVTIKNAATGI western_clawed_frog_PepT1|XP_002935692.1 TADSALIPPFKANEYHTLEQSS--SVTFAYGTNTPQPFPLQDLAEQTRYTCVVKDDG-TA three-spined_stickleback_PepT1a| DPL-LLPAAQASDDFFTFDTETV---GISVG-NS-STVKNITLAKGNRKTLLIT-SSIND China_rockfish_PepT1a|ABV82968.1 DPL-LLPAAQASDEFFTFDLEII---RVSIG-SP-EETKYIPLAKEKRQTLLIP-SNIAD Nile_tilapia_PepT1a| ESL-TLNAAQASDKYFTFETEQI---IVSVG-SP-EMTQIIFLEKKSRQTLLIP-SVISD Japanese_medaka_PepT1a| FTV-HLPPAQASEEYFTYKEQEV---SISIG-NP-PVTETIPLVKGKRQTLLIP-PTIRE mummichog_PepT1a|AEX92274.1 FTDLLLPAAQASDIQN----KKL---AFQQE-TL-RRPKIISLPDGTRNTIVIVEQGPAF southern_platyfish_PepT1a| QF--NLTGAQASEEYFTFESDQI---TVSIG-NP-SVSRDVSLTKEQRQTLLIP-SAIND torafugu_PepT1a| ETPVLLPANQASD-VFTFSDENI---TVSVG-TP-AINQTIQLTKGLRQTLLN----LNQ Atlantic_cod_PepT1a| TV--QLAPGQAS-DYFTFDEDFV---IVSVD-NT-SISQNLTLAKGKRQSVILP-SNNTQ zebrafish_PepT1a|XP_001919914.3 EPL-LIGSFESSPDYITFDQQDI---RLAFNTTP-EINKDLSLIKGSRQTLIIPSE--PA Japanese_eel_PepT1a|BAM67012.1 APL-TVPPFQANPEYLPFSENEI---QVSTG-V--GFTQNIMLEKGKRQTLLINPA--TN common_carp_PepT1b|AEX13747.1 EPF-VVPGFNSSNNYMTLDTENV---TVSAG----GRDATAYFQKESRHTVLINADRM-- red_crucian_carp_PepT1b|AFI42054.1 EPF-VVPGFDSSNDYMTLDKMVV---MVSAG----DRNATAIFVRGKRQTVLMNANGM-- red_crucian_x_common_carp_PepT1b|AFI42056.1 EPF-VAPGFNSSNNYMTLDTENV---TVSAG----GRNATAYFQKESRHTVLINADGM-- red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 EPF-VVPGFNSSNNYMTLDTENV---TVSAG----GRNATAYFQKESRHTVLINADGM-- grass_carp_PepT1b|AET36827.1 EQF-FVPGFNSSNEYMTLDTMNV---TVSVG----GRNETGYFLNKMRHTVLINAGGM-- zebrafish_PepT1b|AAQ65244.1 DQF-MVPGFNASSEYLTLDKENV---TISAG----GVNDTAFLKTGTRHTVLMNAAGM-- Atlantic_cod_PepT1b|AAY17354.1 NF-TLD-PFMSNSKYLSFEGKI----NIDINKT--SMPL--VLTNGTRRSVVIDQTF--P Atlantic_salmon_PepT1b|BAH24102.1 IDVSVPAHQVNTGDYLTFDKSV----RVVFNKNT-STGTDLILMSQTRRTALVSPTL--- southern_platyfish_PepT1b| AF-QLQ-TLQGNEEYYTYNLPF----DLTIDSGP-TETI--RLPGGTRNTIVIVEEAGRM mummichog_PepT1b|AEX92273.1 NF-HLG-AFEGRQDYLTYTEPF----LLTINSGS-PNLI--SLPDGTRNTIVIVEQGPAF spotted_green_pufferfish_PepT1b| PF-SME-PFTARDNYTTFTGAF----NLSLGPGN-SNEI--RFNGSTRNTLEIIQESDSP torafugu_PepT1b| PF-SME-PFTGRDNYTSFTEPF----QLDLGPSA-SEVV--TLENGTRNTLVIIQERAAP Japanese_medaka_PepT1b| VL-PLK-PLTATETYETFKNPF----LLTVGD-Y-EYAV--SFPKGTRNTITIVQNETEL Antarctic_icefish_PepT1b|AAO39705.2 NF-TLK-PFTANEDYLTFGSPF----ALLLGPNA-SFPI--AIEEGNRSTSVIVQEGTRP three-spined_stickleback_PepT1b| KV-TLE-AFTANADYLTFEQHF----DLTVGSDF-NYST--TLTPGSRNTMVIFPDTTPP European_seabass_PepT1b|ACI49693.2 SF-TLE-SYKANEEYFNFNGPF----KLNLGSGN-AFLG--NIPAGTRATIVIIQDGTKP white_grouper_PepT1b|AFP33141.1 EF-TLK-PYTANDDYLTFDDPF----LLNLGGNA-TYLT--GLVDGNRSTVVIVQDGPLP yellow_perch_PepT1b|ACX49753.2 EF-TLQ-PFRANEDYLNFDDTF----ELTLRPNA-TSNI--SLENGNRSTGVIVEDWS-- . : : Supplemental Figure 1

human_PepT1|AAB61693.1 HYQVVKDGLNQKPEKGENGIRFVNTFNELITITMSGKVYANISSYNASTYQFFPSGIK-- chimpanzee_PepT1|XP_522705.3 HYQVVKDGLNQKPEKGENGIRFVNTFNELITITMSGKVYANISSYSASTYQFFPSGIK-- Rhesus_monkey_PepT1|NP_001028071.1 HYRVVKDDLNQKPKKGENGIRFVNTFNELITVTMSGKIYANVSSNNASNYQFFPSGVK-- crab-eating_macaque_PepT1|AAQ56235.1 HYRVVKDDLNQKPKKGENGIRFVNTFNELITVTMSGKIYANVSSNNASNYQFFPSGIK-- house_mouse_PepT1|NP_444309.2 QYRVVKDGLNQKPEKGENGIRFVNTLNEMVTIKMSGKVYENVTSHNASGYQFFPSGEK-- Norway_rat_PepT1|BAA09318.1 LYRVVKDGLNQKPEKGENGIRFVSTLNEMITIKMSGKVYENVTSHSASNYQFFPSGQK-- dog_PepT1|NP_001003036.1 NYRVVKDGLNQKPEKGENGIRFINSLNESLNITMGDKVYVNVTSHNASEYQFFSLGTK-- horse_PepT1|XP_001493109.3 HYRVIKDGLDRKPEKGQNGIRFVNAFDKSFDVTMDGTVYVNVTSHSASEYQFFPSGKK-- pig_PepT1|AAO43094.1 HYRVVKDGLNQKPEKGENGVRFVNTFDESFNVTMDGKVYIDVTSHNASAYQFFPSGAK-- cattle_PepT1|NP_001092848.1 NYQVVKDGLNQKPEKGRNGIRFVNAFGESFNVTMDGEVYNNVSSHNASEYLFFSSGVK-- sheep_PepT1|AAK14788.1 NYQVVKDGLNQKPEKGRNGIRFVNAFGESFGVTMDGEVYNNVSGHNASEYLFFSSGVK-- rabbit_PepT1|AAA17721.1 NYRVVNDGLTQKSDKGENGIRFVNTYSQPINVTMSGKVYEHIASYNASEYQFFTSGVK-- gray_short-tailed_opossum_PepT1|XP_001377037.2 YFVTLKDSLKTKPEKGLNGIRFVNNLDRTINISMDGKTYLNIAPKNASDYEFFSSGEK-- platypus_PepT1|XP_001506250.2 EFTLLENDLNKKPEKGLNGIRFINAMNKSINITVAGSNFQDVLPRNASEYEFFPSGVK-- chicken_PepT1|AAK39954.1 VSSLRSDNFTSKPEEGKNLVRFVNNLPQTVNITMGDTTFGILEETSISNYSPFSGGRT-- turkey_PepT1|AAO16604.1 VSSLRSDNFTSKPEEGKNLIRFVNNLPQTVNITMGDTDFGILEETSISNYTLFSGGRT-- western_clawed_frog_PepT1|XP_002935692.1 IQANVFEDISAKPDQGSNAIRFVNGMQEPINVTLNAVSLGQLMPLQISNYTMQKLGIK-- three-spined_stickleback_PepT1a| N-WVLTNDLISKPQEGNNEIRFINGLSTTINVSAPAADFGVIESFYYSNYSKIKTGKT-- China_rockfish_PepT1a|ABV82968.1 E-WLLTDDLTAKPEEGNNAIRFINGMNAAVNVSTPAAHFGLIESFYYSNYSQITNNYSQI Nile_tilapia_PepT1a| E-WLLTKDLTSKPEQGNNEIRFVNGMNMPVNVTTSAVDLGLIEPFYYSNYSKIKNGEN-- Japanese_medaka_PepT1a| E-WVLIDDLTSKPEEGNNAIRFVNGLATDLNVSTAAVNFGIIEPLTSSNYSLLKNGKH-- mummichog_PepT1a|AEX92274.1 G-YITIDDLTSKPEEGNNAIRFVNGLATDINVSAPAADFGVIESFYMSIYSLLKTGTKT- southern_platyfish_PepT1a| D-WQLAYDLIYKPQEGNNEIRFINGMSTPVNVSSAAVHYDQIEPLHYSNYSEIKNGRA-- torafugu_PepT1a| K-WALSNDLISKPEKGQNSVRFINGMNQIVNISTSEVDFGKIEPFLYSNYTLLKNGMT-- Atlantic_cod_PepT1a| E-WPMTEDLTAKPEQGANAIRFVSGT-YPLNISTGGLDFGITDGSLYSNYSLLTYGST-- zebrafish_PepT1a|XP_001919914.3 E-MYLKEDIKSKPKEGKNAVRFVNGWTAYLNITNLESS---LQPSETSNYTLVSQGMR-- Japanese_eel_PepT1a|BAM67012.1 T-MEAINDLMAKPEQGDNAIRFVNGLGTMVNVTTAAVDFGVIAPSSVSNYTLLHEGKS-- common_carp_PepT1b|AEX13747.1 --LQTLNDITEKPNQGMNAIRFVNGFRSHLNFSVKSDHLGPIAPLQASDYFSVTHGKA-- red_crucian_carp_PepT1b|AFI42054.1 --QSILNDITEKPNQGMNAIRFVNGFRSPLNFSIKSDHLGSIAYLQASDYLIVTHGKA-- red_crucian_x_common_carp_PepT1b|AFI42056.1 --LQTLNDITEKPNQGMNAIRFVNGFRSHLNFSVKSDHLGPIAPLQASDYFSVTHGKA-- red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 --LQTLNDITEKPNQGMNAIRFVNGFRSHLNFSVKSDHLGHIAPLQASDYFSVTHGKA-- grass_carp_PepT1b|AET36827.1 --IQTLNDITDKPSQGGNAIRFVNGFRTQLNITVKSGDLGFLSPLEGSSYLMVPHGKA-- zebrafish_PepT1b|AAQ65244.1 --RNTLDDLTEKPEQGLNAIRFVNGWENRLNVSVKSDNVH-ADPLDASVYLLVPHGKV-- Atlantic_cod_PepT1b|AAY17354.1 N-SISYEDMTAKPEQGENAIRFLNGLGENVNVT----SLGNIPSMKMSKYALVQQGSA-- Atlantic_salmon_PepT1b|BAH24102.1 -DMNLVYDLSKKPDDGMNAIRFVNGLGSALNVTLG---VGDIAPLAVSNYSLVPQGKA-- southern_platyfish_PepT1b| TN-IKFGDVVAKPEEGANAIRFFNGFGMTLNITVGEEGFGNIVSKNMSTYVDVPQGTA-- mummichog_PepT1b|AEX92273.1 GY-ITFQDIVAKPEEGANAIRFFNGYGSVLNITVGDQEYGDIVPNNMSIFINVPQGTG-- spotted_green_pufferfish_PepT1b| HVLAAFSDINKKPEKGKNAIRVLTASARRINVTARENDFGFTVPNNMSAYQLLHSGDV-- torafugu_PepT1b| AY-ITFKDINEKPAKAANAIRIFNGFNETINVTSGEQDFGYSVPNNMSEYRLLHSGHV-- Japanese_medaka_PepT1b| GA-IPFEDITKKPEQGANAIRFFNGFDTALNVTVGDKEIGYIHPNNMSEYTSVKRGYA-- Antarctic_icefish_PepT1b|AAO39705.2 TP-ITFSDTTSKPEQGANAIRFFNGFNMTLNMTWGDQSFGNIPTNDMSTYVLIPQGVA-- three-spined_stickleback_PepT1b| KL-MPFTDINAKPEQGANAIRFFNGLDSDLNVTIGNLDFGDVSANNMSVYVGVPKGSA-- European_seabass_PepT1b|ACI49693.2 RP-TQFRDIKSKPEQGTNAIRFLNGFGSVLNATVGTLEFGNTITNNMSEYISVPQGNA-- white_grouper_PepT1b|AFP33141.1 KP-LGFVDIKTKPEQGANDIRFLNGYDSLLNVTVGDQDFGEITTNSMSKYVGVPRGPA-- yellow_perch_PepT1b|ACX49753.2 PP-VWFTDTKSKPEQGANTIRFLNGLGSDLNVTAGNLFFWVVNKNDMSNYVAVPQGLA-- * .. * :*... . . * :

human_PepT1|AAB61693.1 ----GFTISST-EIPPQCQPNFNTFYLEFGSAYTYIVQ-RKNDS---CP-EVKVFEDISA chimpanzee_PepT1|XP_522705.3 ----GFTISST-EIPPQCQPNFNTFYLEFGSAYTYIVQ-RKNDS---CP-EVKAFEDISA Rhesus_monkey_PepT1|NP_001028071.1 ----GFTISST-EIPPQCQSNFNTFYLEFGSAYTYLVR-RKNGS---CP-EVQSFEDISA crab-eating_macaque_PepT1|AAQ56235.1 ----GFTISST-EIPPQCQPNFHTHYLEFGSAYTYLVR-RKNGS---CP-EVRSFEDISA house_mouse_PepT1|NP_444309.2 ----QYTINTT-AVAPTCLTDFKSSNLDFGSAYTYVIR-RASDG---CL-EVKEFEDIPP Norway_rat_PepT1|BAA09318.1 ----DYTINTT-EIAPNCSSDFKSSNLDFGSAYTYVIRSRASDG---CL-EVKEFEDIPP dog_PepT1|NP_001003036.1 ----NITISSTQQISQNCTKVLQSSNLEFGSAYTYVIG-TQSTG---CP-ELHMFEDISP horse_PepT1|XP_001493109.3 ----SFTINST-EISQQCERNFTSPRLGFGSAYTYVMG-RKADG---CP-ELSVFGDIPP pig_PepT1|AAO43094.1 ----SFIVHSP-EISPQCKNNFTSSSLEFGSAFTYVIT-RKEDS---CP-DLKIFEDISP cattle_PepT1|NP_001092848.1 ----SFTINSP-EISQPCGKEFKTPYLGFGSAFTYVIT-RKSDG---CP-EAKAFEDISP sheep_PepT1|AAK14788.1 ----SFTINSP-EISQQCEKQFKTSYLEFGSAFTYVIS-RKSDG---CP-EPKIFEDISP rabbit_PepT1|AAA17721.1 ----GFTVSSA-GISEQCRRDFESPYLEFGSAYTYLIT-SQATG---CP-QVTEFEDIPP gray_short-tailed_opossum_PepT1|XP_001377037.2 ----TIEIKG------VCS--GKSPRLEFGSAYTYVITKCD-TN---GL-ALKTFNDIPA platypus_PepT1|XP_001506250.2 ----TIMINDK-----QCE--GKTGKLSFGSAYTLVVTKCE-NG---ES-NIIDIEDLSP chicken_PepT1|AAK39954.1 ----YDIVITAG--STNCK--PTSEKLGYGGAYTIVINECS-GD---VT-QLRYIEDIQP turkey_PepT1|AAO16604.1 ----DDIVIVAD--STNCT--VTSEALGYGGAYTIIINECS-ED---VT-QLRYIEDIQP western_clawed_frog_PepT1|XP_002935692.1 ----EIEVFTAS--GKTWK--VESIKFGFGSSYTIIIKEGN-TE----L-QVEYVEDIQP three-spined_stickleback_PepT1a| ----IFTI-RSG--SQSCE---YSRDFGFGSSYTFFIPSTFVFG-PNCQESVTVAEDIKP China_rockfish_PepT1a|ABV82968.1 TNKVHHTI-QSG--SQSCE---YSRDFGFGSSYTLFIPSTLIFG-QNCQESVTAAEDIKP Nile_tilapia_PepT1a| ----KFSL-SSG--SQSCE---YIKDFGFGSSYTFFIPSTFVFG-PNCQDSITVVEDIEP Japanese_medaka_PepT1a| ----TFSL-KSG--SQSCE---YTIKFGFGSSYTIFIPSTFTFG-PNCQESVTEVEEIKP mummichog_PepT1a|AEX92274.1 ----IFTK-NNV--KQSCE---YSRDFGFGSSYTFFIPSTFVFG-PNCQESVTEVENIGP southern_platyfish_PepT1a| ----TFTL-QSG--SQSCE---YSKDFGFGGSYTFFIPSTLTFE-PNCHESITESVDIKP torafugu_PepT1a| ----NFTI-KTA--RQSCY---WTRDFGFGSSYSFFIHSNFSFE-PDCSKSITEIEYIKP Atlantic_cod_PepT1a| ----VFTI-ESG--GESCK---YSREFGFGSSYTLIIPSSFTFG-PDCAASIGVAEDIKP zebrafish_PepT1a|XP_001919914.3 ----KFTL-TDG--IQSCE---FSRKFGFGSSYTFLIPSDL-FS-TDC-ESIKEIEDMQP Japanese_eel_PepT1a|BAM67012.1 ----TFTLTSEG--GQTCQ---FSKTYKFGSSYTLVIPSDIQWT-ENCGDTIKESLDIKP common_carp_PepT1b|AEX13747.1 ----SFTIENEE--GQTCH---YILQLGFGSSYTVLIPNTFTFG-ESCTENIKAIQDINP red_crucian_carp_PepT1b|AFI42054.1 ----NFSIVNQE--GQTCH---YILQLGFGSSYTVLISSNFTFG-ESCTENIKAVEDIEP red_crucian_x_common_carp_PepT1b|AFI42056.1 ----SFTIENEE--GQTCH---YILQLGFGSSYTVLIPNTFTFG-ESCTENIKAVQDINP red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 ----SFTIENEE--GQTCH---YILQLGFGSSYTVLTQTPLL-W-RICTENIKAMQDINP grass_carp_PepT1b|AET36827.1 ----NFTIGNEN--GQNCT---YIMQLGFGSSYTVLIPSTFSFG-QNCNNTITAVQDIEP zebrafish_PepT1b|AAQ65244.1 ----NFTIFDGG--DGKCH---YIMQLGFGSTYTVLIPSTFAFG-QTCSESFEAVQDMEP Atlantic_cod_PepT1b|AAY17354.1 ----QFDIQTVN--G-KCT---YSIAVGFGSAYTVIIPDTFTIA-D-CG-GLRPEEDIGP Atlantic_salmon_PepT1b|BAH24102.1 ----EFTIMNSG--GASCL---YSIDLGFGSAFTLLIPSTFTIGSPDCWQAIQVVEDIQP southern_platyfish_PepT1b| ----EFVIKNAA--GSTCA---FKREFGFGSSYTFIIPPTFILE-ENCEEHIKEVEDIKA mummichog_PepT1b|AEX92273.1 ----KFFMKNNG--GVECV---FSRKFGFGSSYTFLIPPTFVFG-EHCGESIKEVENIKP spotted_green_pufferfish_PepT1b| ----NYKIMTAS--GRSCV---FSQTLKYGSSYTIFIRPDIKFE-EQCTG-VHAVMDISP torafugu_PepT1b| ----NYKIMTMD--GRSCL---FSQTLKYGSSYTLVVQPNITFE-EQCSN-ILVLMDISP Japanese_medaka_PepT1b| ----GYWIRNDA--GLECF---VKQELGFGSSYTLLIPPTLTFE-VNCSEGVQKILDIEP Antarctic_icefish_PepT1b|AAO39705.2 ----QYQIKNAL--GSVCD---YKQELGFGSSYTIVIPPTFNFG-STCEQILIPVVDIKP three-spined_stickleback_PepT1b| ----QFKIKSA---AEECV---YTQELGFGSSFTLIIPPTFAFG-SNCEQSIRPVLDMEQ European_seabass_PepT1b|ACI49693.2 ----QFHIRDNS--GQECV---YTQKLGFGSSYTLIIPPTFAFG-PNCENSIQPVVDIKP white_grouper_PepT1b|AFP33141.1 ----KFLIKSTT--GQECV---YSQELGFGSSFTLIIPPTFTFG-QNCEQNIHPVMDIKP yellow_perch_PepT1b|ACX49753.2 ----KFQIKNDA--GQECN---YDYNLGFGSSITFIIPTIFTFG-PDCGLSIHPVIDIKP :*.: : . : Supplemental Figure 1

10 11 %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% %%%%%%%%%%%%%%%%%%% ################################ ###################### human_PepT1|AAB61693.1 NTVNMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV chimpanzee_PepT1|XP_522705.3 NTVNMALQIPQYCLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV Rhesus_monkey_PepT1|NP_001028071.1 NTVNMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAIGNIIVLIV crab-eating_macaque_PepT1|AAQ56235.1 NTVNMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAIGNIIVLIV house_mouse_PepT1|NP_444309.2 NTVNMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV Norway_rat_PepT1|BAA09318.1 NTVNMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAIGNIIVLIV dog_PepT1|NP_001003036.1 NTVNMALQIPQYFLITCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV horse_PepT1|XP_001493109.3 NTVNMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV pig_PepT1|AAO43094.1 NTINMALQIPQYFLITCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV cattle_PepT1|NP_001092848.1 NTVSMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV sheep_PepT1|AAK14788.1 NTVSMALQIPQYFLLTCGEVVFSITGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV rabbit_PepT1|AAA17721.1 NTMNMAWQIPQYFLITSGEVVFSITGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV gray_short-tailed_opossum_PepT1|XP_001377037.2 NTVNMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV platypus_PepT1|XP_001506250.2 NSVSMALQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV chicken_PepT1|AAK39954.1 NTVHMAWQIPQYFILTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV turkey_PepT1|AAO16604.1 NTVHMAWQIPQYFLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAFGNIIVLIV western_clawed_frog_PepT1|XP_002935692.1 NTIHMALQIPQYFLITAGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV three-spined_stickleback_PepT1a| NSVHMALQIPQYFFITVGEVMFSVTGLEFSYSQAPSNMKAVLQAGWLLTVAVGNFIVLIV China_rockfish_PepT1a|ABV82968.1 NSAHMALQIPQYFFITAGEVMFSVTGLEFSYSQAPSNMKAVLQAGWLFTVAIGNFIVLIV Nile_tilapia_PepT1a| NSVHMALQIPQYFFITAGEVMFSVTGLEFSYSQAPSNMKAVLQAGWLFTVAVGNFIVLIV Japanese_medaka_PepT1a| NSVHMALQIPQYFLITAGEVMFSVTGLEFSYSQAPSNMKAVLQAGWLLTVAVGNFIVLIV mummichog_PepT1a|AEX92274.1 NTVHMALQIPQYFFITVGEVMFSVTGLEFSYSQAPSNMKAVLQAGWLLTVAVGNFIVLIV southern_platyfish_PepT1a| NSVHMALQIPQYFLITAGEVMFSVTGLEFSYSQAPSNMKSVLQAGWLLTNSFGNFIVLIV torafugu_PepT1a| NTAHMALQIPQYFFITAGEVMFSVTGLEFSYSQAPNNMKAVLQAGWLLTVAVGNFIVLIV Atlantic_cod_PepT1a| NSVHMALQIPQYFLITAGEVVFSVTGLEFSYSQAPSNMKAVLQAGWLFTVAIGNFIVLIV zebrafish_PepT1a|XP_001919914.3 NSVHMALQIPQYFLITTGEVMFSVTGLQFSYSQAPKNMKSVLQAGWLCTNAVGNIIVLIV Japanese_eel_PepT1a|BAM67012.1 NTIHMAWQIPQYFLITSGEVVFSVTGLEFSYSQAPSNMKAVLQAGWLFTVAVGNIVVLIV common_carp_PepT1b|AEX13747.1 NDIHMAWQVIQYFLMTCGEVVFSVTGLDFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV red_crucian_carp_PepT1b|AFI42054.1 NGIHMAWQIIQYFLITCGEVVFSVTGLDFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV red_crucian_x_common_carp_PepT1b|AFI42056.1 NDIHMAWQVIQYFLMTCGEVVFSVTGLDFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 NDIHMAWQVIQYFLMTCGEVVFSVTGLDFSYSQAPSNMKSVLQAGWPLTVAVGNIIVLIV grass_carp_PepT1b|AET36827.1 NSVHMAWQIPQYVFLTAGEVMFSITGLEFSYSQAPASMKSVLQAGWLMTVAFGNVIVLIV zebrafish_PepT1b|AAQ65244.1 NRIHMAWQVIQYFLLTCGEVVYSVTGLDFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV Atlantic_cod_PepT1b|AAY17354.1 NVVHMAWQIPQYFLMTMGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLFTVAVGNIIVLIV Atlantic_salmon_PepT1b|BAH24102.1 NTIHMGWQIPQYFLMTGGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLFTVAVGNIIVLIV southern_platyfish_PepT1b| NSIHMAWQIPQYFLMTSGEVVFSVTGLEFSYSQAPSNMKAVLQAGWLLTVAVGNIIVLIV mummichog_PepT1b|AEX92273.1 NSIHMAWQIPQYFLMTSGEVFFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV spotted_green_pufferfish_PepT1b| NTVTLALQIPQYFFITAGEVVFSVTGLEFAYSQSPSNMKAVLQAGWLLTVAVGNIIVLIV torafugu_PepT1b| NTLSLALQIPQYFLITAGEVVFSVTGLEFAYSQSPSNMKSVLQAGWLLTVAVGNIIVLII Japanese_medaka_PepT1b| NTFSMAWQIPQYFLLTAGEVVFSVTGLEFSYSQAPSNMKAVLQAGWLLTVAFGNIIVLIV Antarctic_icefish_PepT1b|AAO39705.2 NIIHMAWQIPQYFLMTVGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIVVLII three-spined_stickleback_PepT1b| NSFHMAWQIPQYFLLTLGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIVVLIV European_seabass_PepT1b|ACI49693.2 NTIHMAWQIPQYFLITAGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIV white_grouper_PepT1b|AFP33141.1 NTIHMAWQIPQYFLITAGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLFTVAVGNIIVLIV yellow_perch_PepT1b|ACX49753.2 NTIHMAWQIPQYFLITAGEVIFSVTGLEFAYSQAPSNVKSVLQAGWLLTVAVGNIIVLIV * :. *: ** ::* ***.:*:***:*:***:* .:*:****** * :.**.:***:

12 %%%%%% %%%%%%%%%%%%%%%%%%%%%%%%%%%% ###### ####################### human_PepT1|AAB61693.1 AGAGQFSKQWAEYILFAALLLVVCVIFAIMARFYTYINPAEIEAQFDEDEKKNRLEK--- chimpanzee_PepT1|XP_522705.3 AGAGQFSKQWAEYILFAALLLVVCVIFAIMARFYTYINPAEIEAQFDEDEKKNRLEK--- Rhesus_monkey_PepT1|NP_001028071.1 AGAGQFSKQWAEYILFAALLLVVCIIFAIMTRFYTYINPAEIEAQFGEDEKKKSLEN--- crab-eating_macaque_PepT1|AAQ56235.1 AGAGQFSKQWAEYILFAALLLVVCIIFAIMTRFYTYINPAEIEAQFDEDEKKKSLEN--- house_mouse_PepT1|NP_444309.2 AGAGHFPKQWAEYILFASLLLVVCVIFAIMARFYTYINPAEIEAQFDEDEKKKGIGK--- Norway_rat_PepT1|BAA09318.1 AEAGHFDKQWAEYVLFASLLLVVCIIFAIMARFYTYINPAEIEAQFDEDEKKKGVGK--- dog_PepT1|NP_001003036.1 AGAGQFSEQWAEYILFAALLLVVCVIFAIMARFYTYVNPAEIEAQFDDDEK-KNLEK--- horse_PepT1|XP_001493109.3 AGAGQFSKQWAEYILFAALLLVVCVIFGIMAQFYTYVNPAEVEAKFDDDEKKKNPEK--- pig_PepT1|AAO43094.1 AGAGQFSEQWAEYVLFAGLLLAVCIIFAIMARFYTYINPAEVEAQFDMDEKKKYLGK--- cattle_PepT1|NP_001092848.1 AGAGQFSEQWAEYVLFAALLLVVCVIFAIMARFYTYINPAEVEAQFDKDDKEDYLEK--- sheep_PepT1|AAK14788.1 AGAGQFSEQWAEYVLFAALLLVVCIIFAIMARFYTYVNPAEIEAQFDEDDKEDDLEK--- rabbit_PepT1|AAA17721.1 AGAGQINKQWAEYILFAALLLVVCVIFAIMARFYTYVNPAEIEAQFEEDEKKKNPEK--- gray_short-tailed_opossum_PepT1|XP_001377037.2 AGAGQFSEQWAEYILFAALLLAVCIIFAIMAYYYTYVNPAEIEAQFDDDEDKKRNGRKAG platypus_PepT1|XP_001506250.2 AGAGQFSEQWVEYFLFAGLLLVVCVIFAIMAYYYQYVNPAEIEAQFDEDEKKKTGDLQPN chicken_PepT1|AAK39954.1 AGASKLSEQWAEYVLFAALLFAVCIIFAVMAYFYTYTDPNEVEAQLDEEEKKKQIKQDPD turkey_PepT1|AAO16604.1 AGASKLSEQWAEYVLFAALLFAVCIIFAVMAYFYTYIDPNEVEAQLDEEEKKKQIKQDPD western_clawed_frog_PepT1|XP_002935692.1 AGASHISQQWAEYVLFAALLVAVCIIFAVMAYFYTYVDPAEIEAQFDEEEKKKNAKEIEA three-spined_stickleback_PepT1a| AELAKLPKQWAEYILFASLLVVVCVIFSIMAHFYTYIDPAEIEAQFNKKVDEVEEEEDD- China_rockfish_PepT1a|ABV82968.1 AEVAKIRKRWVEYVLFASLLVAVCFIFSIMAHFYTYTDPTEIEAQFRKKVDKDDEDDKS- Nile_tilapia_PepT1a| AEIAKLPNKWAEYVLFASLLVLVCIIFSIMAYFYTYIDPSEIEVQFRKKVDDDE-DDKD- Japanese_medaka_PepT1a| AEIAKLPKKWAEFFLFASLLVAVCVIFSIMAYFYTYIDPTEIEAQFSQEKDEEDEDEKD- mummichog_PepT1a|AEX92274.1 AELAKFPKQWAEYFLFASLLVVVCVIFSIMAYFYTYIDPAKIEAQFKKKVDEEEEEEES- southern_platyfish_PepT1a| AEIAKLPKQWTEYILFASLLVAVSIIFSIMASFYTYIDPTAIEAEFKKKIHDDEDDKKK- torafugu_PepT1a| AEIAKLPEQWTEYILFASLLLVVCVIFSVMAYFYTYIDPAEIEAQFRKTTDDDEEDYKF- Atlantic_cod_PepT1a| AELAQIPEQWAEYVLFASLLVAVCVIFSIMAHFYTYMDPAEIEAQFRKKDDDHEVRAEK- zebrafish_PepT1a|XP_001919914.3 AELGKLPKQWAEYVLFASLLVAVSIIFSIMAYFYTYIDPAEIEAEILKQQETDPDKKKK- Japanese_eel_PepT1a|BAM67012.1 AEAAQIPEQWAEYILFAALLIAVCVIFAVMAYFYTYVDPTEIEAQFQKDDSETEKEKEKE common_carp_PepT1b|AEX13747.1 AEAGSLPEQWAEYVLFACLLVAVSIIFAVMAYFYTYMDPAEIEAKFMELEPDDKKRKELE red_crucian_carp_PepT1b|AFI42054.1 AEAGSLPDQWAEYVLFACLLVAVSIIFAVMAYFYTYIDPAEIEAKFMEIKPEDEKKKGLE red_crucian_x_common_carp_PepT1b|AFI42056.1 AEAGSLPDQWAEYVLFACLLVAVSIIFAVMAYFYTYIDPAEVEAKFMELKPEDEKKKGLE red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 AEAGSLPEQWAEYVLFACLLVAVSIIFAVMAYFYTYMDPAEIEAKFMELEPEDKKRKELE grass_carp_PepT1b|AET36827.1 AEGA-GMEQWVEFILFAALLVAVSIIFSIMAYFYTYVDADQLDKIYGADTKDE-KVKSSD zebrafish_PepT1b|AAQ65244.1 AEAGSLPDQWAEYLLFASLLVAVSIIFAIMAYFYTYIDPNEIEAKFKELEPEDKKRKEMQ Atlantic_cod_PepT1b|AAY17354.1 AEVAQLPDQWAEYVLFAALLIFVCVVFSIMAYFYTYTDPAEVEARFAELEPEGKDNDRK- Atlantic_salmon_PepT1b|BAH24102.1 AEAAQLPDQWAEYILFASLLVVVCIVFAIMSYFYTYTDPAEIEAEFRQPEHGPERKR--- southern_platyfish_PepT1b| AEAATLPDQWAEYVLFAALLVLVCIIFAIMAYFYTYIDPVQIEADFANLEPEDEK-K--- mummichog_PepT1b|AEX92273.1 AEAATLPDQWAEYILFSSLLVLVCIIFAIMAYFYTYTDPAKIEALFANPEPDDKE-K--- spotted_green_pufferfish_PepT1b| AEAATLEEQWAEYILFASLLVLVCIIFAIMAYFYTYIDPVKIESQFAHCEPEEEK-K--- torafugu_PepT1b| SQAARLEEKWAEYILFASLLVVVCVIFAIMGYFYTYIDPVKIESQFSQSESEEEK-R--- Japanese_medaka_PepT1b| AEAATLEDQWAEYILFAALLVLVCIIFAIMAYFYTYIDPAKIEAHFANMEYGEKERK--- Antarctic_icefish_PepT1b|AAO39705.2 AEAATLEDQWAEYILFASLLVLVCFIFAFMAYFYTYIDPAKIEAEFAHKEPEEEKKR--- three-spined_stickleback_PepT1b| AEAATLQDQWAEYVLFASLLLVVCVIFAIMAYFYTYIDPAKIEAEFAQIDPKQKEKR--- European_seabass_PepT1b|ACI49693.2 AEAATLPDQWAEYILFASLLILVCIIFAVMAYFYTYLDPAKIEAEFAHEEPEDKEKR--- white_grouper_PepT1b|AFP33141.1 AEAATLPDQWAEYILFASLLLLVCFIFAFMAYFYTYIDPTQEEARFTQKEPEEKERK--- yellow_perch_PepT1b|ACX49753.2 AEAATLSDQWAEYILFASLLLVVCVVFAIMAHFYTYIDPTKIEAQFAEKDPEDKEKR--- : . .:*.*:.**: **. *..:*..* :* * : : Supplemental Figure 1

human_PepT1|AAB61693.1 -----SNPYFM------SGA chimpanzee_PepT1|XP_522705.3 -----SNPYFM------SGA Rhesus_monkey_PepT1|NP_001028071.1 -----SNPYIM------LGA crab-eating_macaque_PepT1|AAQ56235.1 -----SNPYIM------LGA house_mouse_PepT1|NP_444309.2 -----ENPYSS------LEP Norway_rat_PepT1|BAA09318.1 -----ENPYSS------LEP dog_PepT1|NP_001003036.1 -----MNVYST------VTP horse_PepT1|XP_001493109.3 -----ENPYYT------LDS pig_PepT1|AAO43094.1 -----DSLYPK------LDT cattle_PepT1|NP_001092848.1 -----SNPYAK------LDS sheep_PepT1|AAK14788.1 -----SNPYAK------LDF rabbit_PepT1|AAA17721.1 -----NDLYPS------LAP gray_short-tailed_opossum_PepT1|XP_001377037.2 VV---SDPYEK------PDS platypus_PepT1|XP_001506250.2 ------NQNEK------PNT chicken_PepT1|AAK39954.1 LH---G--KES------EA- turkey_PepT1|AAO16604.1 LY---G--KES------EA- western_clawed_frog_PepT1|XP_002935692.1 MG---V--QNG------DGP three-spined_stickleback_PepT1a| KSELQKLEMAKKG--SIKSH------EDEDDADKR- China_rockfish_PepT1a|ABV82968.1 QHEKAEFEMVKKD--SFKSH------DDEDEYEHDK Nile_tilapia_PepT1a| KQQKAEIEMVRRD--SAESY------DDNY--K--- Japanese_medaka_PepT1a| KMRKTEEHVTKRG--SVKSN------DSDNAFKLSK mummichog_PepT1a|AEX92274.1 KLEMNAWPEIHATRSSGKQL------KRGGRLK--- southern_platyfish_PepT1a| ELQKSEFKMEKRDSVSSD------DGDKKHV--- torafugu_PepT1a| --QMAKLEMVKNDSQANSKP------DQT------Atlantic_cod_PepT1a| KERKDSRRSQ-R--SSLEMT------EGTGS----D zebrafish_PepT1a|XP_001919914.3 ---KETLEMEEKE------NEQ-----E Japanese_eel_PepT1a|BAM67012.1 KHEMDSISPEK------K------QHDE-----E common_carp_PepT1b|AEX13747.1 MMTKDNLAYVNNE------TSNNTD red_crucian_carp_PepT1b|AFI42054.1 MMTKDNLAYVNNE------IN-SMD red_crucian_x_common_carp_PepT1b|AFI42056.1 MMTKDNLAYVNNE------IN-SMD red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 MMTKDNLAYVDNE------TSNNTD grass_carp_PepT1b|AET36827.1 SKNNETVAMAD------M zebrafish_PepT1b|AAQ65244.1 MTAKDNMAYVHNE------NTN--- Atlantic_cod_PepT1b|AAY17354.1 ---RRSLELHDRKESLEEEN-QRKSR------SSSEASSHHEAPA Atlantic_salmon_PepT1b|BAH24102.1 ----DQVEMERKDSDCSKSS------KGSDMK------KK--DSVVEQLNQE southern_platyfish_PepT1b| ----KNLEMTKK-DMVENHDEKK------RRSS-N-EGK mummichog_PepT1b|AEX92273.1 ----KNLEMTKK-DMAEKHERRS------SDTSSD-EED spotted_green_pufferfish_PepT1b| ----KKRSLEM----VGHGNGFR------KRSDSSSSD-ETT torafugu_PepT1b| ----KSLEMDHK-DRFGRRNEVR------ERSNSRL-D-EKN Japanese_medaka_PepT1b| ----KSLEMAKK-ASFQHQDEDN------KSSDSSSDE-EEE Antarctic_icefish_PepT1b|AAO39705.2 ----KSVDMSRK-SVDMSRKSVDMSRKSVDMSRKSVDMSRKSVDMSRKSSHSRSEK-DEE three-spined_stickleback_PepT1b| ----RN---SRK-DSVEQHKEER------RSSDSSYD-NEE European_seabass_PepT1b|ACI49693.2 ----KSLEMAKK-DSVEHHKEDR------RSS----DSS----SD-EEE white_grouper_PepT1b|AFP33141.1 ----KSVEMKKK-DSVENRKEGR------KSS----DSSSDSSSD-EEE yellow_perch_PepT1b|ACX49753.2 ----KSVEMTKK-DSVEHRNEDR------RSS----DSS----SD-EEE

human_PepT1|AAB61693.1 NSQKQM chimpanzee_PepT1|XP_522705.3 NSQTQM Rhesus_monkey_PepT1|NP_001028071.1 NSQTQM crab-eating_macaque_PepT1|AAQ56235.1 NSQTQM house_mouse_PepT1|NP_444309.2 VSQTNM Norway_rat_PepT1|BAA09318.1 VSQTNM dog_PepT1|NP_001003036.1 VSQTQM horse_PepT1|XP_001493109.3 VSQTRM pig_PepT1|AAO43094.1 DVQTQM cattle_PepT1|NP_001092848.1 VSQTQM sheep_PepT1|AAK14788.1 VSQTQM rabbit_PepT1|AAA17721.1 VSQTQM gray_short-tailed_opossum_PepT1|XP_001377037.2 FSQTAM platypus_PepT1|XP_001506250.2 VAQTAL chicken_PepT1|AAK39954.1 --VSQM turkey_PepT1|AAO16604.1 --DSRM western_clawed_frog_PepT1|XP_002935692.1 YSQTKM three-spined_stickleback_PepT1a| ---TKM China_rockfish_PepT1a|ABV82968.1 TKQSRM Nile_tilapia_PepT1a| --QSKM Japanese_medaka_PepT1a| M----- mummichog_PepT1a|AEX92274.1 --KSTF southern_platyfish_PepT1a| --QTSM torafugu_PepT1a| ----KL Atlantic_cod_PepT1a| PKENRM zebrafish_PepT1a|XP_001919914.3 IKQTKI Japanese_eel_PepT1a|BAM67012.1 MKQTKI common_carp_PepT1b|AEX13747.1 VKQTKI red_crucian_carp_PepT1b|AFI42054.1 VKQTKI red_crucian_x_common_carp_PepT1b|AFI42056.1 VKQTKI red_crucian_x_common_x_Japanese_crucian_carp_PepT1b|AFI42055.1 VKQTKI grass_carp_PepT1b|AET36827.1 PKQTKM zebrafish_PepT1b|AAQ65244.1 IKQTKI Atlantic_cod_PepT1b|AAY17354.1 DKATNM Atlantic_salmon_PepT1b|BAH24102.1 VKQSKM southern_platyfish_PepT1b| IVQTNF mummichog_PepT1b|AEX92273.1 GKQTNF spotted_green_pufferfish_PepT1b| TRESKL torafugu_PepT1b| TKETRM Japanese_medaka_PepT1b| SKQSKM Antarctic_icefish_PepT1b|AAO39705.2 TLQTKI three-spined_stickleback_PepT1b| QKQTRI European_seabass_PepT1b|ACI49693.2 TKQTKI white_grouper_PepT1b|AFP33141.1 VKQTKI yellow_perch_PepT1b|ACX49753.2 TPQTKI

Supplemental Figure 1. Alignment of vertebrate PEPT1 amino acid sequences. Multiple sequence alignment was obtained by Clustal Omega using default parameters. GenBank Acc. No. is indicated for the annotated sequences only. Putative transmembrane domains (1-to-12) are indicated according to Newstead et al. (2011) [Newstead S, Drew D, Cameron AD, Postis VL, Xia X, Fowler PW, Ingram, JC, Carpenter, EP, Sansom MS, McPherson MJ, Baldwin SA & Iwata S (2011). Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2. EMBO J 30, 417-426] (#) and Solcan et al. (2012) [Solcan N, Kwok J, Fowler PW, Cameron AD, Drew D, Iwata S & Newstead S (2012). Alternating access mechanism in the POT family of oligopeptide transporters. EMBO J 31, 3411-3421] (%). The Thr-to-Ile substitution discussed in the manuscript (ref. position T327 in rabbit PEPT1 and I334 in zebrafish PEPT1) is boxed.