Genetic and evolutional mechanisms explain associated malformations--a 'G-E-M' concept

During the process of evolution, segmented structures like heart and kidneys appeared earlier than vertebral column. Single piece notochord was transformed into segmented vertebral column. Ribs followed the segmented vertebral column but preceded the fore limbs in evolution. Segmentation is the underlying principle of the body plan even in annelids and arthropods. In these animals apart from vertebral column; segmentation is obvious in other structures like kidneys and heart. Somewhere on the temporal axis of evolution--vertebral column, heart and kidneys have evolved together; and have shared the genetic control of embryological morphogenesis. Mutations or micro-evolution in homeotic--Hox--genes led to macro evolution and a sudden change in morphology, when six-legged insects diverged from crustacean-like arthropod ancestors with multiple limbs. The control of embryonic morphology has been highly conserved in evolution between vertebrates and invertebrates and Hox genes occupy a central role in the scheme of molecular control of early morphogenesis. Mutations affecting regulatory genes, including those containing homeobox sequences, have been important. Malformations and association like VACTERL can be rationally explained considering the genetic and evolutional mechanisms controlling morphogenesis.