Fig. 3.

Proposed beneficial and deleterious effects of variation in Olduvai copy number. Shown are the proposed ways in which Olduvai dosage may be contributing in advantageous and detrimental ways to human brain evolution and cognitive disease, respectively. The specific supporting evidence for these relationships is described in separate sections devoted to (1) human brain evolution, (2) autism and schizophrenia, and (3) microcephaly and macrocephaly. The “risk” arrow is meant to show that 1q21-associated duplications and deletions, that encompass many Olduvai copies, have been linked with autism and schizophrenia risk, respectively. The “severity” arrow is meant to show that Olduvai (e.g., CON1) dosage has been linearly associated with the severity of autism and, in the opposite manner with schizophrenia positive symptom severity. While the dosage variation of the Olduvai subtype CON1 is compatible with the proposal that autism symptoms and schizophrenia positive symptoms exhibit diametric phenotypes, a more complete description of the relationships between Olduvai and these disorders is provided in the text