Msx Domain Evolution Model. The Msx protein is represented here by a horizontal line overlain by boxes that represent the Msx Homology domains discussed in the text. Presumed loss of the MH1C domain is indicated by asterisks. Inferred ancestral chromosomal segments with homology to human chromosomal paralogons at 4p16, 5q35, 8p and 10q26 are indicated along internal branches. Abbreviations: MYA = Million Years Ago; HsChr p = Homo sapiens Chromosome paralogon ; MtHox = MetaHox; R1, R2 or R3 = Round 1, 2 or 3; WGD = whole genome duplication. Archeolog = ancestral sequence. Estimated divergence times are taken from the following sources:1 = R1 WGD, origin of craniates = 520 MYA; 687 +/- 156 MYA ; 2 = divergence of Chondrichthyes from Osteichthyes = 450 MYA[109, 110]. The elephant shark has four Hox clusters, orthologous to known clusters in tetrapods, suggesting Chondrichthyes diverged after the second round of WGD but did not undergo an additional round of duplication as did the osteichthyes. R2 WGD, origin of jawed vertebrates, divergence from agnathans, 477 MYA ; 507 +/- 104 MYA, ; 3 = divergence of Actinopterygia and Sarcopterygia = 416 MYA ; 450 MYA ; 4 = R3 WGD within the Actinopterygia = 320 MYA ; 350 MYA ; 5 = evidence for a 4,5 and 8,10 paralogon split [85, 86].