Subject: methuselah family of GPCRs Dear Gillian, .. for a small part of a manuscript we have almost accepted in Science for the A. gambiae genome issue this Fall I have worked up the methuselah family of GPCrs. I see that West et al named the genes last year in PNAS in a mth-like series, abbreviated mthl in my work .. Anyway, the annotations of these proteins remain somewhat poor in the public databases, so I'm not sure if they have been updated to what they published. Any case, I've also added two members, 13 and 14, by fixing the annotation of GH30018 and recognizing RE31310p as a family member, respectively. Below is a simple FASTA compilation of the resultant family. I've done this pretty carefully with detailed alignments of intron positions, etc, and am pretty confident of them from a bioinformatic perspective, and several now have full-length cDNAs, but if you have questions about any of them please let me know. Hugh >mth MKTLLVLRISTVILVVLVIQKSYADILECDYFDTVDISAAQKLQNGSYLFEGLLVPAILTGEYDFRILPDDSKQKVAR HIRGCVCKLKPCVRFCCPHDHIMDNGVCYDNMSDEELAELDPFLNVTLDDGSVSRRHFKNELIVQWDLPMPCDGMFYL DNREEQDKYTLFENGTFFRHFDRVTLRKREYCLQHLTFADGNATSIRIAPHNCLIVPSITGQTVVMISSLICMVLTIA VYLFVKKLQNLHGKCFICYMVCLFMGYLFLLLDLWQISISFCKPAGFLGYFFVMAAFFWLSVISLHLWNTFRGSSHKA NRFLFEHRFLAYNTYAWGMAVVLTGITVLADNIVENQDWNPRVGHEGHCWIYTQAWSAMLYFYGPMVFLIAFNITMFI LTAKRILGVKKDIQNFAHRQERKQKLNSDKQTYTFFLRLFIIMGLSWSLEIGSYFSQSNQTWANVFLVADYLNWSQGI IIFILFVLKRSTWRLLQESIRGEGEEVNNSEEEISLENTTTRNVLL >mthl1 MDRSRSSRAASSNQFIRPCGLLTTVILLQTLVSMSLAIEEMSPPPAAPPRPSPPPTVKLNKCCHSGEYLNDGTCIAGS EALWLPMVYLVQQQRFFEPHGASPRFLKFLPNTRPTCRKDQTTEIFRSRGANVMLFPNGTLYVRERALMVQPSDYCVD WEVAVVCLNDSQPINALEDPDYAANPLVQQEPPKASLRLSKCCGKWGSYNTQLQNCDLQPNHQAAVDGLLRLSPQLPE GSYQTSYGLPDCGQPGGYSIAGDWQDAKLDRNTAMLQLPHKNLSAGQYCLEHTQREGEVKIIACQHLFSSAAGAGIHD GSIGGTIEQANGQNLQKAVLTGGILVSIVFLSATLVAGFLLPAVHHALHWRCQICYVTCLLFGKILLAIEELSSSLQP GSAACHTLAITMQFFFLAAFFWLNTMCFNIWWTFRDFRPSSLERNQEALRRYLYSLYAWGGPLLITFVAACVDQLPET TLLRPGFGQLYCWFDNRNLSIFAYFYGPIGLLLCANIALFVSTTHQLTCGLWKRDDVKSSSEKSALGRVCLKLVVVMG VTWIADILSWLVGGPHGVWFFTDLINALQGVFIFIVVGCQPQVWTACRRIFCPRLRHDITNTTNGVQHSSSSQGLPSM AGGTEITQNTTTTTTTTNTTATHMPSNPAEDEVPEKAPIAPVAPIVKMETIC >mthl2 MLLSASILIYFLLNLQSSSAEIADCSFYDTVDISEGQRLSNGSYLYEGLLIPAHLTAKYEFKLLANGDKEQVPSHVRG CVCKLRTCVRFCCPHDHIMDMGECYANMTTEENELLDPMLNVTLDDGSVVQRHYKKELMVQWDLPKPCDDMFYLDNRD IMDEYTLFENGRLLRHYDQVYLDKSEYCLQHRTFGEGNNNSIRIIPHNCLILPSRTGQTVVMITSLICLVLTIAVYLC VKKLMNLEGKCFICYMMCLFFGYLFLLLDLWELSLDFCKAAGFLGYFFVMAAFFWLSIISRHYWKCLTNPCASMNIRS ERAFLLYSCFAWAMPLALTGVTYLADNVVNNEEWQPRVGDEGHCWIYTKSWSAMVYFYGPMVLLILFNITMFVLTAKH IIDSKRTLRKIARNEGRIQKLNSDKQNYTQFLLLFTVMGMSWSFEIFSYLVQREKLWVNIFLVADYFNWSQGVIIFVL FILRRKTLVLFKKQIFPKQRAFSRSATQSTIESISQTKRHFNMT >mthl3 MRIVIGSFTAFLLLLLQNSNAEIPGCDFFDTVDISKAPRFSNGSYLYEGLLIPAHLTAEYDYKLLADDSKEKVASHVR GCACHLRPCIRFCCPQYQKMQKSKCYGDMSEDELNKHDPFVNVTLSDGSVVRRHFKEDLIVQSDLAKPGCPRMYFLNH ELPGNEFTLFENGSLLRHWDKVELSKREYCVQHLSFKDDSIRIAPHFCPLSSEHSRTWKTVAIVISLICIILTISVYL YVEKLRNLHGKCFICYLASLFLGYFFLVLNVWKYSSGFCVTAGFLGYFSVIAAFFWLSVISLTLWNSFSGNSSWLNRF LPQNRFLSYNLYAWGMALLLTAITYIADQVVKNEKLRPRVGVGKNCWIYTGDMTVMIYFYGPMLLIIVFNITMFVLTA FRIMKVKKEAQNFTQQQKTTNRLNSDKQTYALFLRLFIIMGLSWSLEIISFLLSKNQAWAKAFMVADYFNWSQGTVIF LLFVLRPSTLKLLKERIKGGRDEAGASDEHISLQNTKIDPSVF >mthl4 MRILLIAVLFLLMPKSNAEIPGCDFFDTVDISKAPRFSNGSYLYEGLLIPAHLTAEYDYKLLADDSKEKVASHVRGCA CHLRPCIRFCCPQYQKMQKSKCYGDMSEDELNKHDPFVNVTLSDGSVVRRHFKEDLIVQSDLAKPGCPRMYFLNHELP GNEFTLFENGSLLRHWDKVELSKREYCVQHLSFKDDSIRIAPHFCPLSSEHSRTWKTVAIVISLICIILTISVYLYVE KLRNLHGKCFICYLASLFLGYFFLVLNVWKYSSGFCVTAGFLGYFSVMAAFFWLSVIGIHLRIKFSLASNCLHRLLPE NPFRAYNLYAWGIPLIMTAITYTADQVVKNEKLRPRVGVGKNCWIYTGDMTVMIYFYGPMLLLIAFNIIMFVLSAIYI YNIKKNVKGLVHKQQTNQQINDQQMFAIFLRLFILMGLSWSFEILSFLLTKQQAWARALMVADYFNWSQGTIIFVLFI LKPSILKLIIAGGRQNLPGSHHNSRSKAARYNSTHTACEGSIADPNAYC >mthl5 MLVKTLGAHFAAGQNAKKCSCCALLISLLCVLLLSLNPLPVTSHVTSAGSSTALSSDPNLVLFNKCCEKFEIHVDHEC QQVNETDYFQPMFTSYGGEQNRPVKFKFVIGIPNCGSMQMWPIYHYAGSSDKLVLLDDGRLRHYTNAENEAEERHGIQ SDYEEDIAGSLEPLYHDYDKGLYCIDKATSSTGEENVLFANICLARKEIKWSDSNFLLRKILNPIFHGISLVILLVIA IIYFILPTLRDLVGNIVTTIAMCLMVSQAADLVRIFTELTSHVSFIVADIILCFSLLAAFFWLNSFGFYIWKTFRSRN VFLRVTDGRKYCYYSAYAWGCTATMAALAVFAHFFLDAESYKQEHMVGEQETIGWLGICIFFAPIACTILVNIFFYVT TRKLINRRTVYGRIAHKLKANFIMFSLMLLVMSIAWLFLIMSWLQMEGLLYAHIVVNALQTPLLLYICVLRQRHVTFL LKKTCCYNEPPSANDWGDELHYMNGNDY >mthl6 MLLNILAIILVFVISSQSEAVIPGCDYFDTVDISHIPKLNDSYAYEELIIPAHLTGLYTFRQLADGSQEPVKSHLRAC ICKLKPCIRFCCPRNKMMPNSRCSDGLTENLKRINPYLKITLEDGTIGKYYLLTDMIVLRYEFRYCEKVVSVQEDQYK LYENGSFMIKPDVNWTLSKQWYCLHPRLEDPNSIWILEHVYIPKSMPAVPQVGTISMVGCILTIAVYLYIKKLRNLLG KCFICYVFCKFVQYLIWAGGDLNLWNNICSLAGYTNYFFALASHFWLSVMSHQIWKNLRLINRDERSYHFLIYNIYGW GTPAIMTAITYLVDWAWEDRPDKLNWIPGVGLYRCWINTYDWSAMIYLYGPMLILSLFNVVTFILTVNHIMKIKSSVK SSTQQQRKCIQNNEFLLYLRLSVMMGVTGISEVITYFVKRHKFWRQVLRVPNFFHLGSGIVVFVLFILKRSTFQMIME RISGPRRQQPAS >mthl7 MRLPWVIFCTVLLLIFTNNSNADIPGCNYYDTVDISYIERQNDSYLYDDIEIPASLTGYYEFRQFGDGSITPIEKHLR ACVCSVRPCIRICCPAKNFLANGKCDDGLKEELARFKPYIYFTYMDLQARVPLTDMAIIRDEFFDCDEMIYISDFNYF LEEDGKFWVTVDLFMEKQDYCLYRHNFDSDFPKSMWIIRHRCTSHISPGSLEILIITMICFVLTIAVYLYIKKLRNVT GKCIVCCIVSRFIQCLIMILDHLNLLNGICSPAGYSSHFFRMASNLWLSVISYHTWKVLTSLNRVDPNYRFLRYNAFV WSTAAIMTGSIYIVNQIWENDPSKWNWLPLVGFIRCSVKDWHPSVWIYISGPSLALSTFNVAMFALTAIYIRKVKGGI NKFTNEEEGRINCINFDSQTYLQFLRLSIVMGLTWIFNVIPYSARLHIFWEWVGIISEYFHSAFGIVLFVLLVLKRST WTLMMDS >mthl8 MAQFCILGVLLILSGTHCSWGFHEETHYPCAFIDTANITGSYGLDGPFVHNWTVIPRHFVAVYDFVIENGIRIPASRH LRACVCKTKPCVRICCLRGEIYDLEKRQCLVPVAGVSSLPSHSHMEVELGNGSLRLVKLQPRFSIHVETPCEHMKAVT KGSEYVHWTLHENGTISHRGHIFSKHYCFTPLLHGNSTWEWQPLACAPEKLYFVLGVREWTYAICLLIAILSMFIVLM VYLMCSEMRNSFYGVAIKAYAICMILGYALLAYLTLHNPANLSNAACRILPSLALMNLVLSFYILSFIAFKLYLSFYG VVFTKLMFWLIFTPIVLVAVGWSFFVGFSYYGSRLIFGGDTCWFDPRNWSVMIYFYAPVFVACAISGFFYVLSQIYIR DQPDIETEKSFESIEKNRFKSFWKYFGYTAVVWVVCICSFAFNYYWENRSHLNYAVSFCMAFHGFAALYALIGKNQQI QNFLRRIDNGEDTCENSVPLSSFG >mthl9 MVSPLIILLIIWLSVGAKSVEIASINHPCAYAHTVNITDGLRMKDGSYSYAGVVVPPHLMAEYSFKVIDGVEYRAKKH LRGCVCLLKPCISFCCPENLVFDAKHWNCTMPHQVRESTHVELTYANRTVDQVRIRDRFVVRTELGCRNKFVDKKHDN FWQWDLFENGTLRRDNRLWSTDEYCFSPLEHNPEQWELTPLNCERFQTGYRVWIYAICSIIAIIINIFILSLLGSVRD ARKSHYGQLIIYYLLSMIVGYSLLVYLALKNPMKLSHVACRNIGFLAYFCIMLSFVFLAICSLDFLLKFKQKAVRSSV RRLSLALAVLAVIGLRFLVSLAQDSKLPKHFKPGMGEDYCWFDVRTWGILIYYYGPIALLLIFSIVCCLKAYFSIYEL PPDTQYILGTQLKIVKTHFYAFSAYIVGVFAVWIREIVVYIMARVREHFFIIDFWSGICILGLAIAGFILLLGKNLHV KSWWAINVESSQTDLSIINARVYKFDEKGDLKSSDSPYKPTVTSL >mthl10 MPKKIHQPGGSLYCGVTLLGVLCLVVFRLIPGIPFGTYVMAERDHYHTIDDPNVPCNFYDTVNLTGHRLFPNGSYDYY GTIVPAELVGTYDYIHSSLTERIEVREHVRGCVCKFKSCLNICCPWRQVFNSEVDGCIIDHSDNRTWPDPPMLNITFR NESTILVNMFTQFAIQSFRPCPKMFSLQPETNNWDDYLLFENGSMLRVDDKLLIRKNEFCMVPTYVNESDMFYTIHPA NCDMQDDHSTVKIINSYAMMFSIPFMMLTIAVYLLIPELRNQHGKSLVCYLIGLSVGYSSLCYVQLYQVDATGVTCKV FGYTAYFFFMGAYMWLSVISFDLWHNFRGTRGINRFQEKKRFLFYSLYSWGIALVFLAFTYCAQQLTNLPANLKPGIG DGVYCWLDMSNWAAMIYFYGPILAIVVANTIMFIMTAIKIHGVQREMARIIASENSTKNLRTEKDKFGLFLRLFLIMG ITWLTELISYFVGSDKGWSKLFYISDLANAMQGFLIFMLFVMKKKVKHLITNRCSSVRDGSNQRQSQYSTKTTSSSVA NLSLHEKPSVEKPLVISSSVDPQKTTIFR >mthl11 MGMFRVEYLLLGILVIGVRSRDIPNCDFFDTVQLRESEKLCNGSYRYEDVVIPAKLTGKYDYEIDYDGDRVSVPKHIR GCVCKLKTCIRFCCHHKKLMAGNLCSQDVYENLTYEYTLDITQLNGSVIKKHVLNDMVVQQDLPLPCERHYSLDAETS TYDMWSLYENGSLFRHFDQRYLSKQEFCLQPNPTSTGKNYSLIVAFNCIQKPSMKMAYVKFSSVFFMVITIAAYLWLP KFRSLHGKCCNLYFICLAITFLLNVISLFGIFELKTPICYLTGYAGYFTVMATFLWLSVISFDVWRRFAMRKFQVFYK NKRSSFFNYNIIVWSSAGLLTCIIFLVDQFVETNLDNPYNPAVGVFSCWIFTNGWSATFYFYAPLAILIILNCASFFL TTRYIYVENKQNQKVLNNSEPQKLSRNHANYRIYFRLFIIMGGSWFLEIIAFICEMENMWKPLIILNDYINCSQGIII FVATFCNHEMFRLIRKRIQNRNITSLELTNTSRPVESEKMADVELGK >mthl12 MFLWLKCFCTLIIVTIAKNSSAKIPHCKYDETINISHFKRLNDAYIYEHFEIPANLTGEFDYKELMDGSKVPTEFPNL RGCICKVRPCIRICCARKNILSNGECSDGVKNEIKLTMLDLTMQDILLTDPTLAELNMIPQYNSTELLILREQFQPCD EIVSLKRDEYTIFKDGSILLHTSAEILSNDQYCLYPEIYSDFPETIRIINRRCYRNVMPGIAQLSVISVVGFILTLAV YLSVEKLRNLLGKCLICSLFSMFMEYFIWTMDYFRLLQSICSAAGYMKYFFSMSSYLWFSVVSFHLWELFTSLNRHEP QYRFLIYNTFVWCTAAIPTVVIFSMNQMWENDPGKSEWLPLVGYFGCSVKDWNSSSWFYSHIPIVILNSFNVIMFVLT AIYIWKVKKGVKSFAQHDERNTTCLEFNVQTYIQFVRLFLIMGASWLLDQLTRLAEDSHLLLDTIVLNLTVYLNAAFG ILIFVLLILKGSTFKMIMERIRGTRFMTCLKGNQ >mthl13 MKLQLLGTFLVLILLQFQAVNTDSNKTEEDSCVKSDDDNSNDEDDLWHCIPICCPRKNMMANGGCSFKEHLFRTKLDL NIRLDDNSTEALYFNNQTLLITSFWDIDEMMGLRRDEYTLYKNGTIYIHSDQSIQTKEEYCFYPHQIYSDFPETIWII SHKFSSIESPGAFELASGSIICYIIIFGIYLFVKELRNDFGKCVMSCVFCLFLDYLIWLMDELRLLDDFCSLTGYIMF FFDFANSVWFSIISYCIWKKITSVVSQENRDQFVFYSTFAYGISAIPLGIIISINQFWEEDLRKWNWLPLVGFYLLQF SDCKRSSWVYYFVPYAIMCAINIIMFVLTIKHIMKTKRNLHNLTKRPDRNETCVTVNFLNFELYLLFLRISGIMGVAW ILIIFLLIEVNSTFWDIFGIIIQQIHYGFGIILFVLLIFKRSTHQLLIAKIRGKNLHQQTDV >mthl14 MNLGHWNFLLALISLQTFFNASAQISTVNNSSKGSNNSNIFHEDTFNSTSIDVLDASIHSTLVVPQTYSTEAATISGA RFATSVPVQSPVDNPLDPADCSQREKYRKQPVATPSSRLRKCCPHGENLNIYRENQSDSMCDNGLLSFEPTIISAVLF DNCIEDLEVETTLDYDIGNPCNSSLLYDDKDDVFFVLQDGSLLIIDKFGNESYTVKEHYCLDIDKSGHLFAFTCVTQV EEQIAFAKVVFVAVLMLISMPCLLLVSYLHMTLRLLRNLHGLSLSLMSLCLASGYFVHSVVHIYGIPNQGFIGYVIQF CILSYFFWYLCICFNVLLNVWYKLPCCIQCSKSWATFNFACYAVFAFSGPATIVALTVQKGLPGMPSYFLQGLTESIR DSQRYFIPPVSTILFLSFLLNIISFFGFQRISGYAKAEKNIQERKCLFDQQKYEDVKKDAKCVSLLGIIMVVSWLLEI ITFYSGSNSNYLILCDMVNGLQGVWVLLIFLVVRRRRTIILRWWYDRGSHEIEGTELQALSNSPT Hugh M. Robertson, Professor Department of Entomology, University of Illinois at Urbana-Champaign 320 Morrill Hall, 505 S. Goodwin Ave., Urbana, IL 61801