35:
242:
Synonymous changes may not be neutral because certain codons are translated more efficiently (faster and/or more accurately) than others. For example, when a handful of synonymous changes in the fruit fly alcohol dehydrogenase gene were introduced, changing several codons to sub-optimal synonyms,
92:; since some of the codons for a given amino acid differ by just one base pair from others coding for the same amino acid, a mutation that replaces the "normal" base by one of the alternatives will result in incorporation of the same amino acid into the growing
222:
In the above phenylalanine example, suppose that the base in position 3 of a TTT codon got substituted to a C, leaving the codon TTC. The amino acid at that position in the protein will remain a phenylalanine. Hence, the substitution is a synonymous one.
268:
signals. When the splicing signal is destroyed by a synonymous mutation, the exon does not appear in the final protein. This results in a truncated protein. One study found that about a quarter of synonymous variations affecting exon 12 of the
243:
production of the encoded enzyme was reduced and the adult flies showed lower ethanol tolerance. Many organisms, from bacteria through animals, display biased use of certain synonymous codons. Such
200:, indicating that translation should stop), some amino acids are coded for by 2, 3, 4, or 6 different codons. For example, the codons TTT and TTC both code for the amino acid
1227:
710:
Kahali B, Basak S, Ghosh TC (March 2007). "Reinvestigating the codon and amino acid usage of S. cerevisiae genome: a new insight from protein secondary structure analysis".
107:
Since there are 22 codes for 64 codons, roughly we should expect a random substitution to be synonymous with probability about 22/64 = 34%. The actual value is around 20%.
270:
1015:
671:"Experimental reduction of codon bias in the Drosophila alcohol dehydrogenase gene results in decreased ethanol tolerance of adult flies"
264:
Another reason why synonymous changes are not always neutral is the fact that exon sequences close to exon-intron borders function as
1175:
154:
results in a change in amino acid that may be arbitrarily further classified as conservative (a change to an amino acid with similar
17:
1055:
1343:
622:"In vivo introduction of unpreferred synonymous codons into the Drosophila Adh gene results in reduced levels of ADH protein"
236:
383:
Chamary JV, Parmley JL, Hurst LD (February 2006). "Hearing silence: non-neutral evolution at synonymous sites in mammals".
1207:
823:
1315:
1086:
1008:
211:. There are two mechanisms for redundancy: several different transfer RNAs can deliver the same amino acid, or one
1469:
1413:
239:, meaning that it does not affect the fitness of the individual carrying the new gene to survive and reproduce.
1408:
545:
1560:
1496:
1427:
1168:
196:(in nature) and a stop signal (i.e. up to three codons that do not code for any amino acid and are known as
1550:
1232:
1001:
530:
1555:
1447:
1142:
982:
292:
155:
151:
932:
1565:
1491:
1279:
1192:
1161:
249:
193:
111:
28:
326:
Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM (January 2007).
1575:
1452:
1269:
1254:
1081:
1457:
1382:
1274:
816:
175:
1372:
1357:
1237:
1060:
1045:
937:
901:
864:
302:
131:
123:
1479:
1377:
1295:
1050:
846:
758:
574:
483:
339:
8:
1305:
1040:
1024:
911:
851:
258:
138:
to the rare codon can affect the timing of translation, and in turn the co-translational
115:
77:
47:
972:
962:
957:
762:
578:
487:
343:
1440:
1323:
781:
747:"Synonymous mutations in CFTR exon 12 affect splicing and are not neutral in evolution"
746:
646:
621:
563:"The rate of molecular evolution considered from the standpoint of population genetics"
506:
471:
452:
408:
365:
219:
in position three of the anti-codon, which recognises more than one base in the codon.
38:
Point substitution mutations of a codon, classified by their impact on protein sequence
597:
562:
205:
1570:
1106:
1032:
896:
891:
809:
786:
727:
692:
687:
670:
651:
602:
541:
511:
400:
357:
287:
93:
1524:
456:
412:
369:
1127:
1091:
967:
916:
776:
766:
719:
682:
641:
633:
592:
582:
501:
491:
442:
392:
347:
244:
143:
101:
85:
1501:
1338:
1184:
1132:
1122:
1065:
906:
637:
496:
232:
139:
88:", meaning that some amino acids are coded for by more than one three-base-pair
1328:
1300:
883:
751:
Proceedings of the
National Academy of Sciences of the United States of America
723:
567:
Proceedings of the
National Academy of Sciences of the United States of America
297:
57:
96:
when the gene is translated. Synonymous substitutions and mutations affecting
1544:
1529:
1216:
1101:
254:
201:
97:
771:
352:
1403:
1333:
1202:
859:
790:
731:
696:
655:
587:
515:
404:
361:
265:
81:
54:
606:
1506:
1435:
1096:
472:"Non-silent story on synonymous sites in voltage-gated ion channel genes"
282:
216:
197:
328:"A "silent" polymorphism in the MDR1 gene changes substrate specificity"
1464:
179:
993:
247:
may arise for different reasons, some selective, and some neutral. In
127:
61:
34:
447:
430:
396:
327:
1484:
1474:
1398:
832:
1153:
104:; however, it is not always the case that the mutation is silent.
1220:
147:
73:
182:. Each of these amino acids is coded for by a sequence of three
163:
1242:
470:
Zhou T, Ko EA, Gu W, Lim I, Bang H, Ko JH (31 October 2012).
188:
159:
89:
305:, where more than 20-22 natural encoded amino acids are used
801:
212:
135:
119:
69:
65:
1212:
183:
325:
257:
folding stability, with mRNA encoding different protein
192:. Because there are 64 possible codons, but only 20-22
166:
amino acid), or radical (vastly different amino acid).
130:, rendering the synonymous mutation non-silent. The
744:
712:
382:
271:
cystic fibrosis transmembrane conductance regulator
253:synonymous codon usage has been shown to influence
169:
1542:
709:
619:
80:is not modified. This is possible because the
1169:
1009:
817:
424:
422:
321:
319:
745:Pagani F, Raponi M, Baralle FE (May 2005).
469:
1324:Precursor mRNA (pre-mRNA / hnRNA)
1176:
1162:
1016:
1002:
824:
810:
431:"Synonymous mutations break their silence"
235:occurs, the change is often assumed to be
53:though they are not always silent) is the
780:
770:
686:
645:
596:
586:
505:
495:
446:
419:
351:
316:
126:, any of which could alter the resulting
951:Mutation with respect to overall fitness
273:gene result in that exon being skipped.
33:
1023:
668:
538:Nature Encyclopedia of the Human Genome
14:
1543:
620:Carlini DB, Stephan W (January 2003).
560:
428:
1344:Histone acetylation and deacetylation
1157:
997:
805:
528:
1409:Ribosome-nascent chain complex (RNC)
27:For words related to "synonym", see
1183:
24:
876:Mutation with respect to structure
25:
1587:
1087:Models of nucleotide substitution
110:A synonymous mutation can affect
688:10.1111/j.1420-9101.2004.00725.x
1414:Post-translational modification
738:
675:Journal of Evolutionary Biology
204:. This is often referred to as
703:
662:
613:
554:
522:
463:
376:
170:Degeneracy of the genetic code
13:
1:
309:
261:preferring different codons.
831:
497:10.1371/journal.pone.0048541
226:
7:
276:
158:), semi-conservative (e.g.
142:. This is reflected in the
10:
1592:
1143:Nonsynonymous substitution
933:Chromosomal translocations
724:10.1016/j.bbrc.2007.01.038
638:10.1093/genetics/163.1.239
429:Goymer P (February 2007).
293:Nonsynonymous substitution
152:nonsynonymous substitution
26:
1517:
1426:
1391:
1365:
1356:
1314:
1288:
1262:
1253:
1191:
1115:
1074:
1031:
950:
925:
882:
875:
839:
178:involves a set of twenty
156:physiochemical properties
146:that is observed in many
76:, such that the produced
1475:sequestration (P-bodies)
669:Carlini DB (July 2004).
561:Kimura M (August 1969).
385:Nature Reviews. Genetics
250:Saccharomyces cerevisiae
215:can have a non-standard
29:Synonym (disambiguation)
18:Synonymous substitutions
1453:Gene regulatory network
1138:Synonymous substitution
1082:Models of DNA evolution
973:Nearly neutral mutation
772:10.1073/pnas.0502288102
435:Nature Reviews Genetics
353:10.1126/science.1135308
44:synonymous substitution
1458:cis-regulatory element
983:Nonsynonymous mutation
938:Chromosomal inversions
840:Mechanisms of mutation
588:10.1073/pnas.63.4.1181
536:. In Cooper DN (ed.).
531:"Single Base Mutation"
140:folding of the protein
39:
1061:Stabilizing selection
1046:Directional selection
963:Advantageous mutation
902:Conservative mutation
303:Expanded genetic code
231:When a synonymous or
132:substrate specificity
100:are often considered
37:
1561:Protein biosynthesis
1480:alternative splicing
1470:Post-transcriptional
1296:Transcription factor
1051:Disruptive selection
958:Deleterious mutation
926:Large-scale mutation
186:base pairs called a
1551:Molecular evolution
1404:Transfer RNA (tRNA)
1116:Molecular processes
1041:Balancing selection
1025:Molecular evolution
978:Synonymous mutation
912:Frameshift mutation
763:2005PNAS..102.6368P
579:1969PNAS...63.1181K
488:2012PLoSO...748541Z
344:2007Sci...315..525K
259:secondary structure
209:of the genetic code
194:encoded amino acids
78:amino acid sequence
1518:Influential people
1497:Post-translational
1316:Post-transcription
1056:Negative selection
164:positively charged
64:for another in an
40:
1556:Molecular biology
1538:
1537:
1422:
1421:
1352:
1351:
1228:Special transfers
1151:
1150:
1033:Natural selection
991:
990:
946:
945:
897:Missense mutation
892:Nonsense mutation
757:(18): 6368–6372.
338:(5811): 525–528.
288:Missense mutation
94:polypeptide chain
16:(Redirected from
1583:
1363:
1362:
1260:
1259:
1178:
1171:
1164:
1155:
1154:
1128:Gene duplication
1092:Allele frequency
1018:
1011:
1004:
995:
994:
968:Neutral mutation
917:Dynamic mutation
880:
879:
826:
819:
812:
803:
802:
796:
794:
784:
774:
742:
736:
735:
707:
701:
700:
690:
666:
660:
659:
649:
617:
611:
610:
600:
590:
573:(4): 1181–1188.
558:
552:
551:
535:
529:Graur D (2003).
526:
520:
519:
509:
499:
467:
461:
460:
450:
426:
417:
416:
380:
374:
373:
355:
323:
245:codon usage bias
144:codon usage bias
102:silent mutations
46:(often called a
21:
1591:
1590:
1586:
1585:
1584:
1582:
1581:
1580:
1566:Gene expression
1541:
1540:
1539:
1534:
1513:
1448:Transcriptional
1418:
1387:
1348:
1339:Polyadenylation
1310:
1284:
1249:
1243:Protein→Protein
1194:
1187:
1185:Gene expression
1182:
1152:
1147:
1133:Silent mutation
1123:Gene conversion
1111:
1070:
1066:Selective sweep
1027:
1022:
992:
987:
942:
921:
907:Silent mutation
871:
835:
830:
800:
799:
743:
739:
708:
704:
667:
663:
618:
614:
559:
555:
548:
533:
527:
523:
468:
464:
448:10.1038/nrg2056
427:
420:
397:10.1038/nrg1770
381:
377:
324:
317:
312:
279:
233:silent mutation
229:
172:
122:transport, and
32:
23:
22:
15:
12:
11:
5:
1589:
1579:
1578:
1576:Neutral theory
1573:
1568:
1563:
1558:
1553:
1536:
1535:
1533:
1532:
1527:
1525:François Jacob
1521:
1519:
1515:
1514:
1512:
1511:
1510:
1509:
1504:
1494:
1489:
1488:
1487:
1482:
1477:
1467:
1462:
1461:
1460:
1455:
1445:
1444:
1443:
1432:
1430:
1424:
1423:
1420:
1419:
1417:
1416:
1411:
1406:
1401:
1395:
1393:
1389:
1388:
1386:
1385:
1380:
1375:
1369:
1367:
1360:
1354:
1353:
1350:
1349:
1347:
1346:
1341:
1336:
1331:
1326:
1320:
1318:
1312:
1311:
1309:
1308:
1303:
1301:RNA polymerase
1298:
1292:
1290:
1286:
1285:
1283:
1282:
1277:
1272:
1266:
1264:
1257:
1251:
1250:
1248:
1247:
1246:
1245:
1240:
1235:
1225:
1224:
1223:
1205:
1199:
1197:
1189:
1188:
1181:
1180:
1173:
1166:
1158:
1149:
1148:
1146:
1145:
1140:
1135:
1130:
1125:
1119:
1117:
1113:
1112:
1110:
1109:
1107:Fay and Wu's H
1104:
1099:
1094:
1089:
1084:
1078:
1076:
1072:
1071:
1069:
1068:
1063:
1058:
1053:
1048:
1043:
1037:
1035:
1029:
1028:
1021:
1020:
1013:
1006:
998:
989:
988:
986:
985:
980:
975:
970:
965:
960:
954:
952:
948:
947:
944:
943:
941:
940:
935:
929:
927:
923:
922:
920:
919:
914:
909:
904:
899:
894:
888:
886:
884:Point mutation
877:
873:
872:
870:
869:
868:
867:
862:
854:
849:
843:
841:
837:
836:
829:
828:
821:
814:
806:
798:
797:
737:
718:(3): 693–699.
702:
681:(4): 779–785.
661:
632:(1): 239–243.
612:
553:
546:
521:
482:(10): e48541.
462:
418:
375:
314:
313:
311:
308:
307:
306:
300:
298:Point mutation
295:
290:
285:
278:
275:
228:
225:
171:
168:
9:
6:
4:
3:
2:
1588:
1577:
1574:
1572:
1569:
1567:
1564:
1562:
1559:
1557:
1554:
1552:
1549:
1548:
1546:
1531:
1530:Jacques Monod
1528:
1526:
1523:
1522:
1520:
1516:
1508:
1505:
1503:
1500:
1499:
1498:
1495:
1493:
1492:Translational
1490:
1486:
1483:
1481:
1478:
1476:
1473:
1472:
1471:
1468:
1466:
1463:
1459:
1456:
1454:
1451:
1450:
1449:
1446:
1442:
1439:
1438:
1437:
1434:
1433:
1431:
1429:
1425:
1415:
1412:
1410:
1407:
1405:
1402:
1400:
1397:
1396:
1394:
1390:
1384:
1381:
1379:
1376:
1374:
1371:
1370:
1368:
1364:
1361:
1359:
1355:
1345:
1342:
1340:
1337:
1335:
1332:
1330:
1327:
1325:
1322:
1321:
1319:
1317:
1313:
1307:
1304:
1302:
1299:
1297:
1294:
1293:
1291:
1287:
1281:
1278:
1276:
1273:
1271:
1268:
1267:
1265:
1261:
1258:
1256:
1255:Transcription
1252:
1244:
1241:
1239:
1236:
1234:
1231:
1230:
1229:
1226:
1222:
1218:
1214:
1211:
1210:
1209:
1208:Central dogma
1206:
1204:
1201:
1200:
1198:
1196:
1190:
1186:
1179:
1174:
1172:
1167:
1165:
1160:
1159:
1156:
1144:
1141:
1139:
1136:
1134:
1131:
1129:
1126:
1124:
1121:
1120:
1118:
1114:
1108:
1105:
1103:
1100:
1098:
1095:
1093:
1090:
1088:
1085:
1083:
1080:
1079:
1077:
1073:
1067:
1064:
1062:
1059:
1057:
1054:
1052:
1049:
1047:
1044:
1042:
1039:
1038:
1036:
1034:
1030:
1026:
1019:
1014:
1012:
1007:
1005:
1000:
999:
996:
984:
981:
979:
976:
974:
971:
969:
966:
964:
961:
959:
956:
955:
953:
949:
939:
936:
934:
931:
930:
928:
924:
918:
915:
913:
910:
908:
905:
903:
900:
898:
895:
893:
890:
889:
887:
885:
881:
878:
874:
866:
863:
861:
858:
857:
856:Substitution
855:
853:
850:
848:
845:
844:
842:
838:
834:
827:
822:
820:
815:
813:
808:
807:
804:
792:
788:
783:
778:
773:
768:
764:
760:
756:
752:
748:
741:
733:
729:
725:
721:
717:
713:
706:
698:
694:
689:
684:
680:
676:
672:
665:
657:
653:
648:
643:
639:
635:
631:
627:
623:
616:
608:
604:
599:
594:
589:
584:
580:
576:
572:
568:
564:
557:
549:
543:
540:. MacMillan.
539:
532:
525:
517:
513:
508:
503:
498:
493:
489:
485:
481:
477:
473:
466:
458:
454:
449:
444:
440:
436:
432:
425:
423:
414:
410:
406:
402:
398:
394:
391:(2): 98–108.
390:
386:
379:
371:
367:
363:
359:
354:
349:
345:
341:
337:
333:
329:
322:
320:
315:
304:
301:
299:
296:
294:
291:
289:
286:
284:
281:
280:
274:
272:
267:
262:
260:
256:
252:
251:
246:
240:
238:
234:
224:
220:
218:
214:
210:
208:
203:
202:phenylalanine
199:
195:
191:
190:
185:
181:
177:
167:
165:
161:
157:
153:
149:
145:
141:
137:
133:
129:
125:
121:
117:
113:
112:transcription
108:
105:
103:
99:
98:noncoding DNA
95:
91:
87:
83:
79:
75:
72:coding for a
71:
67:
63:
59:
56:
52:
50:
45:
36:
30:
19:
1507:irreversible
1392:Key elements
1289:Key elements
1203:Genetic code
1193:Introduction
1137:
977:
860:Transversion
754:
750:
740:
715:
711:
705:
678:
674:
664:
629:
625:
615:
570:
566:
556:
537:
524:
479:
475:
465:
438:
434:
388:
384:
378:
335:
331:
266:RNA splicing
263:
248:
241:
230:
221:
206:
187:
173:
109:
106:
82:genetic code
58:substitution
55:evolutionary
51:substitution
48:
43:
41:
1358:Translation
1195:to genetics
1097:Ka/Ks ratio
283:Ka/Ks ratio
217:wobble base
198:stop codons
180:amino acids
176:translation
124:translation
1545:Categories
1502:reversible
1465:lac operon
1441:imprinting
1436:Epigenetic
1428:Regulation
1383:Eukaryotic
1329:5' capping
1280:Eukaryotic
1102:Tajima's D
865:Transition
547:0333803868
310:References
207:redundancy
160:negatively
86:degenerate
1373:Bacterial
1270:Bacterial
847:Insertion
441:(2): 92.
227:Evolution
128:phenotype
1571:Mutation
1485:microRNA
1399:Ribosome
1378:Archaeal
1334:Splicing
1306:Promoter
1275:Archaeal
1219: →
1215: →
852:Deletion
833:Mutation
791:15840711
732:17258174
697:15271077
656:12586711
626:Genetics
516:23119053
476:PLOS ONE
457:29882152
413:25713689
405:16418745
370:15146955
362:17185560
277:See also
174:Protein
116:splicing
1238:RNA→DNA
1233:RNA→RNA
1221:Protein
782:1088389
759:Bibcode
647:1462401
607:5260917
575:Bibcode
507:3485311
484:Bibcode
340:Bibcode
332:Science
237:neutral
148:species
134:of the
74:protein
60:of one
1075:Models
789:
779:
730:
695:
654:
644:
605:
598:223447
595:
544:
514:
504:
455:
411:
403:
368:
360:
49:silent
1366:Types
1263:Types
534:(PDF)
453:S2CID
409:S2CID
366:S2CID
189:codon
150:. A
90:codon
68:of a
787:PMID
728:PMID
693:PMID
652:PMID
603:PMID
542:ISBN
512:PMID
401:PMID
358:PMID
255:mRNA
213:tRNA
136:tRNA
120:mRNA
84:is "
70:gene
66:exon
62:base
1217:RNA
1213:DNA
777:PMC
767:doi
755:102
720:doi
716:354
683:doi
642:PMC
634:doi
630:163
593:PMC
583:doi
502:PMC
492:doi
443:doi
393:doi
348:doi
336:315
184:DNA
162:to
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318:^
118:,
114:,
42:A
1177:e
1170:t
1163:v
1017:e
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1003:v
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