Evidence for reduced BRCA2 functional activity in Homo sapiens after divergence from the chimpanzee-human last common ancestor
Jinlong Huang,
Yi Zhong,
Alvin P. Makohon-Moore,
Travis White,
Maria Jasin,
Mark A. Norell,
Ward C. Wheeler,
Christine A. Iacobuzio-Donahue
Affiliations
Jinlong Huang
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Yi Zhong
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Alvin P. Makohon-Moore
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Travis White
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Maria Jasin
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Mark A. Norell
Division of Paleontology, American Museum of Natural History, New York, NY 10024, USA
Ward C. Wheeler
Division of Invertebrate Zoology, American Museum of Natural History, New York, NY 10024, USA
Christine A. Iacobuzio-Donahue
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Corresponding author
Summary: We performed a comparative analysis of human and 12 non-human primates to identify sequence variations in known cancer genes. We identified 395 human-specific fixed non-silent substitutions that emerged during evolution of human. Using bioinformatics analyses for functional consequences, we identified a number of substitutions that are predicted to alter protein function; one of these mutations is located at the most evolutionarily conserved domain of human BRCA2.
