Human Genetics

, Volume 115, Issue 5, pp 377–386

Positive selection in MAOA gene is human exclusive: determination of the putative amino acid change selected in the human lineage

  • Aida M. Andrés
  • Marta Soldevila
  • Arcadi Navarro
  • Kenneth K. Kidd
  • Baldomero Oliva
  • Jaume Bertranpetit
Original Investigation

DOI: 10.1007/s00439-004-1179-6

Cite this article as:
Andrés, A.M., Soldevila, M., Navarro, A. et al. Hum Genet (2004) 115: 377. doi:10.1007/s00439-004-1179-6

Abstract

Monoamine oxidase A (MAOA) is the X-linked gene responsible for deamination and subsequent degradation of several neurotransmitters and other amines. Among other activities, the gene has been shown to play a role in locomotion, circadian rhythm, and pain sensitivity and to have a critical influence on behavior and cognition. Previous studies have reported a non-neutral evolution of the gene attributable to positive selection in the human lineage. To determine whether this selection was human-exclusive or shared with other species, we performed a population genetic analysis of the pattern of nucleotide variation in non-human species, including bonobo, chimpanzee, gorilla, and orangutan. Footprints of positive selection were absent in all analyzed species, suggesting that positive selection has been recent and unique to humans. To determine which human-unique genetic changes could have been responsible for this differential evolution, the coding region of the gene was compared between human, chimpanzee, and gorilla. Only one human exclusive non-conservative change is present in the gene: Glu151Lys. This human substitution affects protein dimerization according to a three-dimensional structural model that predicts a non-negligible functional shift. This is the only candidate position at present to have been selected to fixation in humans during an episode of positive selection. Divergence analysis among species has shown that, even under positive selection in the human lineage, the MAOA gene did not experience accelerated evolution in any of the analyzed lineages, and that tools such as Ka/Ks would not have detected the selective history of the gene.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Aida M. Andrés
    • 1
    • 4
  • Marta Soldevila
    • 1
  • Arcadi Navarro
    • 1
  • Kenneth K. Kidd
    • 2
  • Baldomero Oliva
    • 3
  • Jaume Bertranpetit
    • 1
  1. 1.Unitat de Biologia Evolutiva, Departament de Ciències Experimentals i de la SalutUniversitat Pompeu Fabra (UPF)BarcelonaSpain
  2. 2.Department of GeneticsYale University School of MedicineNew HavenUSA
  3. 3.Laboratori de Bioinformàtica Estructural (GRIB)Universitat Pompeu FabraBarcelonaSpain
  4. 4.Department of Molecular Biology and GeneticsCornell UniversityIthacaUSA