Source Data Figure 1. Amino acid sequences of ancestral anCas. >FCA_anCas MKKDYSIGLDIGTNSVGWAVTDDNYNLVRKKMKVLGNTDKKSIGKALWGVRLFDAAETAE ERRMHRTTRRRYTRRRQRIDLLQEIFQEEISKVDPSFFIRLNESRLHPEDKTDDRHPLFG DNETDKDYHKQYPTIYHLRKHLMESDEKHDIRLVYLALHHIIKYRGHFLIEGDLNSENTD VEELFKQLVQVFNDTFEEEHLSEEAIDIEEILTDKKSRSTRAKEVVKLFGSEKKQACISA LIKLIVGLKGNLKKVFGDAEDTSIHFSKDNYEEDLEAIRDIIPDEYADLFEAIKALYDAI VLSGILGGSTSNTKAKVSASMIARYEQHQKDLKQLKQFVKEHLPEKYNEIFSDNTKNGYS AYIEGGTSQEDFYKYLKKILKELEEAEYLLEEIENENFLPKQRTSDNGVIPYQIHLEELR AILKNQGKYYPFLKENAEKIESILTFRIPYYVGPLARGNGRFAWMIRKKDGKITPWNFDE VVDKEKSAEEFIERMTNNCTYLPGENVLPKNSLLYEKFTVLNELNNVRLTTDKGKTRRFS AEQKQEIFDDLFRKNRKVTKKKLEDYLKREYEEFDSADISGIDGEFKSSLGSYHDFCKIV VKGNSLDEEDYKDIIEEIIKWLTVFEDRKMLRRRLEKYSEILTEEQIKKICKRHYTGWGR LSRKLLTGIRDKETGKSIIDVLRETDSSNRNFMQLLSDEDLSFKEEIEQANAEAEGENLH EIVEDLPGSPAIKRGILQALKIVDEIVKVMGHEPKNIFVEMARENQKTGRGRRSTKKRLK RLQEALKNLGSNLLKELPRDDNELRNDRLFLYYTQMGKCMYTGEPIDLDDLSNYDIDHII PQSFIKDDSLDNRVLVSREENARKTDNFPSPEIRRKMKSFWQMLLKAGLISKKKFDRLTR ADRGDFTDDELAGFIARQLVETRQITKHVATLLKQRYPTEKDEEDKTIRNAKIVSVKANL VSEFRQDFGLYKCREVNDYHHAHDAYLNAVVGNALLKKYPQLAAEFIKGDYRKNNAREEN KANAKMHFYSNIMNSFTSDVKIADETGEIVWDKEKDIATVRKVMNYHQVLITRKVEEEKG GFFDQTILSKGNSKKLIPLKKNLDPEKYGGYNSPTVAYSVLVEYDIEKGKKKKLKTVKQL VGIPIRERAKLEKNPIKYLEKKGYQNPKVDLLIKIPKNSLFELDGGRRRILAAAKELKNA NQLVLPAEEYTLLDKVAKIIKKNNSESIEYVEEHLSEFDELLESLIDYSPKLALQDKNLE KIKEAFEQLNLADKKEVAKEIINLLHCTATTANAALKFLGGSKNRMRYTSIKELLNASLI HQSITGLYETRIDLGKLGED >BCA_anCas MKKDYSIGLDIGTNSVGWAVITDDYKVVRKKMKVLGNTDKKSIKKNLWGVRLFDSGETAE DTRLKRTTRRRYTRRRNRICYLQEIFQEEMNKVDDSFFHRLDESFLVPEDKKYDRHPIFG NLEEEVAYHEQYPTIYHLRKHLADSSEKADLRLVYLALAHIIKYRGHFLIEGDLNTENTD VEELFKQFVQVYNQTFEEQHLSDETIDVEEILTEKVSKSRRAENVLKLFPNEKKNGLFGQ LIKLIVGLQGNFKKVFDLSEDAKLQFSKDTYEEDLENLLAMIGDEYADLFLAAKNLYDAI LLSGILTTTDNNTKAKLSASMIKRYEEHQKDLAQLKQFIKEHLPDKYNEIFSDSSKNGYA GYIEGKTSQEDFYKYLKKILSKIDGAEYFLEKIEQENFLRKQRTFDNGVIPHQIHLEELR AILRRQGKYYPFLKENQEKIEQILTFRIPYYVGPLARGNSRFAWLTRKSDEPITPWNFDE VVDKEKSAEAFIERMTNYDTYLPNEKVLPKHSLLYEKFTVFNELTKVRYVTDRGKTQNFS AEQKQEIFDDLFKKNRKVTKKKLENYLKKEYEYFDSPDITGIEDEFNASLGTYHDLLKIL KSKDFLDDEENEEILEDIVKILTVFEDRKMIRKRLEKYSDILTEEQLKKLERRHYTGWGR LSRKLINGIRDKQSGKTILDYLIDDDSSNRNFMQLINDDNLSFKEEIEKAQVIGETENLH EIVQDLPGSPAIKKGILQSLKIVDELVKVMGHEPKNIVVEMARENQTTSRGRRNSKQRLK RLEEALKNLGSNLLKEHPVDNQQLQNDRLYLYYLQNGKDMYTGQELDIDNLSNYDIDHII PQSFIKDNSIDNRVLVSSEENRGKSDNVPSKEVVRKMKSFWQKLLNAGLISQRKFDNLTK AERGGLTEDDKAGFIKRQLVETRQITKHVANILDSRFNTEKDEEDNTIRNVKIITLKSNL VSQFRKDFGLYKVREINDYHHAHDAYLNAVVGTALLKKYPQLEPEFVYGDYRKNNAREEN KATAKKHFYSNIMNFFASEVKIADETGEIVWDKEKDIATVRKVLSYHQVNIVKKVEVQKG GFSKETILPKGNSNKLIPRKNNWDPKKYGGFDSPTVAYSVLVTYDIEKGKKKKLKTVKEL VGITIMERSAFEKNPIAYLEKKGYQNPQEDVLIKLPKYSLFELENGRRRMLASAKELQKG NQMVLPAHLVTLLYHAKRIDKSNNSESLEYVEEHRNEFDELLDYIIDFSEKYILADKNLE KIKKLYEQNNEADIKELAKSFINLLTFTAMGAPAAFKFFGETIDRKRYTSIKELLNATLI HQSITGLYETRIDLGKLGED >SCA_anCas MKKPYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKQSIKKNLLGALLFDSGETAE ATRLKRTARRRYTRRRNRICYLQEIFSEEMNKVDDSFFHRLDESFLVPEDKKYDRHPIFG NLAEEVAYHEQYPTIYHLRKHLADSTEKADLRLVYLALAHIIKFRGHFLIEGDLNAENTD VQKLFQQFVEVYNQTFEESHLSEETIDVEEILTEKISKSRRLENLIKHFPNEKKNGLFGN LIALILGLQPNFKTNFDLSEDAKLQFSKDTYEEDLENLLAQIGDEYADLFLAAKNLYDAI LLSGILTVTDNSTKAPLSASMIKRYEEHQKDLAQLKQFIKEHLPDKYNEIFSDKSKNGYA GYIEGKTSQEDFYKYLKKILSKIDGAEYFLDKIDREDFLRKQRTFDNGSIPHQIHLQELH AILRRQGEYYPFLKENQEKIEKILTFRIPYYVGPLARGNSRFAWLTRKSDEKITPWNFDE VVDKESSAEAFIERMTNYDTYLPNEKVLPKHSLLYETFTVYNELTKVKYVTERGKTQQFF SAEQKQEIFDHLFKKNRKVTKKKLKDYLEKEFEEFDSVDITGVEDEFNASLGTYHDLLKI LKDKDFLDDEENEEILEDIVLTLTLFEDREMIRKRLEKYSDLFTKEQLKKLERRHYTGWG RLSRKLINGIRDKQSGKTILDYLIDDGSSNRNFMQLINDDSLSFKEEIEKAQVIGETDNL HEVVQDLAGSPAIKKGILQSLKIVDELVKVMGRHNPENIVVEMARENQTTNRGRRNSRQR LKRLEEALKNLGSNILKEHPVDNQQLQNDRLYLYYLQNGKDMYTGEELDIDNLSQYDIDH IIPQSFIKDNSIDNRVLTSSEENRGKSDNVPSIEVVRKMKSFWQKLLNAGLISQRKFDNL TKAERGGLTEDDKAGFIKRQLVETRQITKHVAQILDSRFNTERDENDKRIRNVKIITLKS NLVSQFRKDFGLYKVREINDYHHAHDAYLNAVVGTALLKKYPKLEPEFVYGDYKKYNLRK LIAKSDRERGKATAKMFFYSNIMNFFKTEVKLADGTVIERPVIETNKETGEIVWDKEKDF ATVRKVLSYPQVNIVKKVEVQTGGFSKESILPKGNSDKLIPRKNNWDPKKYGGFDSPTVA YSVLVVADVEKGKAKKLKTVKELVGITIMERSAFEKNPIAFLEKKGYQNIQEDLIIKLPK YSLFELENGRRRLLASAKELQKGNEMVLPAHLVTLLYHAKRIDKSNGNSENLEQKQEYVE KHKNEFDELLDYIIDFSEKYILADKNLEKIKELYDQNDDADINELASSFINLLTFTALGA PAAFKFFGETIDRKRYTSTKEVLNATLIHQSITGLYETRIDLSKLGED >PCA_anCas MKKPYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDRQSIKKNLIGALLFDSGETAE ATRLKRTARRRYTRRKNRICYLQEIFSEEMAKVDDSFFHRLEESFLVPEDKKYDRHPIFG NLADEVAYHENYPTIYHLRKKLADSTEKADLRLIYLALAHIIKFRGHFLIEGDLNAENTD VQKLFHQLVDTYNQLFEEDQLDTETIDAKAILTAKISKSRRLENLISQIPGQKKNGLFGN LIALSLGLTPNFKSNFDLSEDAKLQLSKDTYEEDLDNLLAQIGDQYADLFLAAKNLSDAI LLSDILTVNDESTKAPLSASMIKRYEEHQQDLALLKQLVKEQLPEKYKEIFSDKSKNGYA GYIDGKTSQEEFYKYIKPILSKLDGAEEFLAKIDREDFLRKQRTFDNGSIPHQIHLEELH AILRRQEEYYPFLKDNQEKIEKILTFRIPYYVGPLARGNSRFAWLTRKSDEAITPWNFEE VVDKEASAQAFIERMTNFDTYLPNEKVLPKHSLLYETFTVYNELTKVKYVTEGMTKPQFL SAEQKQAIVDLLFKKNRKVTVKQLKEDYFKKIECFDSVDITGVEDRFNASLGTYHDLLKI IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEKRLAKYADLFDKKVLKKLKRRHYTGWG RLSRKLINGIRDKQSGKTILDFLKADGFANRNFMQLINDDSLSFKEEIEKAQVIGQTDSL HEVVADLAGSPAIKKGILQTIKIVDELVKVMGRHNPENIVIEMARENQTTAQGIKNSRQR MKRLEEVLKKLGSNILKEHPVDNTQLQNDRLYLYYLQNGKDMYTGQELDIDNLSQYDIDH IIPQSFIKDNSIDNKVLTSSEENRGKSDNVPSIEVVRKMKSYWQKLLNAGLISQRKFDNL TKAERGGLTESDKAGFIKRQLVETRQITKHVAQILDSRFNTERDENDKPIRNVKIITLKS KLVSDFRKDFGLYKVREINDYHHAHDAYLNAVVGTALLKKYPKLEPEFVYGDYKKYDLRK LIAKSDKERGKATAKMFFYSNIMNFFKTEVKLANGTIIKRPVIETNEETGEIVWDKEKDF ATVRKVLSYPQVNIVKKTEVQTGGFSKESILPKGNSDKLIPRKNNWDPKKYGGFDSPTVA YSVLVVAKVEKGKAKKLKTVKELVGITIMERSAFEKNPIAFLEAKGYQDIQEDLIIKLPK YSLFELENGRRRLLASAKELQKGNEMVLPAHLVTFLYHASRIDKSTGSSENLEQKQEYVE QHKHEFDEILDYIIDFSERYILADKNLEKIKSLYNQNDDSDINELASSFINLFTFTALGA PAAFKFFDATIDRKRYTSTKEVLNATLIHQSITGLYETRIDLSQLGGD >PDCA_anCas MDKKYSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAE ATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFG NIVDEVAYHEKYPTIYHLRKKLADSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSD VDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGN LIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAI LLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYA GYIDGGASQEEFYKFIKPILEKMDGTEELLAKLNREDLLRKQRTFDNGSIPHQIHLGELH AILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEE VVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFL SGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKI IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRHYTGWG RLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSL HEQIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQTTQKGQKNSRER MKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDH IVPQSFIKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL TKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK MIAKSEQEIGKATAKRFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDF ATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVA YSVLVVAKVEKGKAKKLKSVKELVGITIMERSSFEKNPIDFLEAKGYKDVQKDLIIKLPK YSLFELENGRRRMLASAGELQKGNEMVLPAKLVTFLYHASHIEKSKGSPENNEQKQAYIE QHKHDLDEILEYISEFSKRYILADKNLSKVKSLFNKHEDSSISELASSIINLFTLTSLGA PAAFKFLDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD