Knowledge of how genetic factors modulate cingulate development and function may shed light on the unique evolutionary history of this area in humans. The anterior cingulate arises from the medial (limbic) and medial-dorsal telencephalic pallium. These cortical regions show remarkable evolutionary conservation among mammals, birds, and reptiles in contrast to dorsal telencephalic pallium or neocortex, which is highly divergent in volume and microstructure. For these reasons, the cingulate gyrus is often referred to as a phylogenetically "ancient" structure. Whereas this appears to be true in the case of most mammals, analyses of cingulate cortical microstructure in humans show a remarkable leap of recent evolution. Betz, in 1881, first noted the presence of large motor neurons in the cingulate region of humans but not in other great ape species. Similarly, Patrick Hof and John Allman have found spindle cells, so named for their elongate and gradually tapering morphology, predominantly in layer Vb in the medial wall of the cingulate gyrus. These cells are not seen in old world primates but are found in bonobos, chimpanzees, and humans. Phylogenetic studies comparing human and primate genomic sequence data have attempted to explain this recent evolutionary leap. Studies of the role of the DRD4 gene in human evolution and migration show a high correlation (0.8) between the frequency of the exon III seven-repeat allele and miles of migration. Migration was estimated for ethnic groups around the world as the human population expanded out of Africa. The DRD4 gene has undergone strong positive selection during primate evolution. Additional studies of genes that contribute to the development and physiology of the cingulate gyrus may shed light on the evolution of this important brain area. Most importantly, many of these genes may serve as useful molecular targets for pharmacologic intervention for the treatment of psychiatric disorders.

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