Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans

P D Evans, J R Anderson, E J Vallender, S L Gilbert, C M Malcom, S Dorus, B T Lahn

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

A prominent trend in the evolution of humans is the progressive enlargement of the cerebral cortex. The ASPM (Abnormal spindle-like microcephaly associated) gene has the potential to play a role in this evolu-tionary process, because mutations in this gene cause severe reductions in the cerebral cortical size of affected humans. Here, we show that the evolution of ASPM is significantly accelerated in great apes, especially along the ape lineages leading to humans. Additionally, the lineage from the last human/chimpanzee ancestor to humans shows an excess of non-synonymous over synonymous substitutions, which is a signature of positive Darwinian selection. A comparison of polymorphism and divergence using the McDonald-Kreitman test confirms that ASPM has indeed experienced intense positive selection during recent human evolution. This test also reveals that, on average, ASPM fixed one advantageous amino acid change in every 300 000-400 000 years since the human lineage diverged from chimpanzees some 5-6 million years ago. We therefore conclude that ASPM underwent strong adaptive evolution in the descent of Homo sapiens, which is consistent with its putative role in the evolutionary enlargement of the human brain.
LanguageEnglish
Pages489-494
Number of pages6
JournalHuman Molecular Genetics
Volume13
Issue number5
DOIs
StatusPublished - 2004

Fingerprint

Microcephaly
Pan troglodytes
Hominidae
Cerebral Cortex
Genes
Amino Acids
Mutation

Cite this

Evans, P. D., Anderson, J. R., Vallender, E. J., Gilbert, S. L., Malcom, C. M., Dorus, S., & Lahn, B. T. (2004). Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Human Molecular Genetics, 13(5), 489-494. https://doi.org/10.1093/hmg/ddh055

Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. / Evans, P D; Anderson, J R; Vallender, E J; Gilbert, S L; Malcom, C M; Dorus, S; Lahn, B T.

In: Human Molecular Genetics, Vol. 13, No. 5, 2004, p. 489-494.

Research output: Contribution to journalArticle

Evans, PD, Anderson, JR, Vallender, EJ, Gilbert, SL, Malcom, CM, Dorus, S & Lahn, BT 2004, 'Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans', Human Molecular Genetics, vol. 13, no. 5, pp. 489-494. https://doi.org/10.1093/hmg/ddh055
Evans PD, Anderson JR, Vallender EJ, Gilbert SL, Malcom CM, Dorus S et al. Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Human Molecular Genetics. 2004;13(5):489-494. https://doi.org/10.1093/hmg/ddh055
Evans, P D ; Anderson, J R ; Vallender, E J ; Gilbert, S L ; Malcom, C M ; Dorus, S ; Lahn, B T. / Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. In: Human Molecular Genetics. 2004 ; Vol. 13, No. 5. pp. 489-494.
@article{96e8c25fc5c54195a6e4ad2a4858a6aa,
title = "Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans",
abstract = "A prominent trend in the evolution of humans is the progressive enlargement of the cerebral cortex. The ASPM (Abnormal spindle-like microcephaly associated) gene has the potential to play a role in this evolu-tionary process, because mutations in this gene cause severe reductions in the cerebral cortical size of affected humans. Here, we show that the evolution of ASPM is significantly accelerated in great apes, especially along the ape lineages leading to humans. Additionally, the lineage from the last human/chimpanzee ancestor to humans shows an excess of non-synonymous over synonymous substitutions, which is a signature of positive Darwinian selection. A comparison of polymorphism and divergence using the McDonald-Kreitman test confirms that ASPM has indeed experienced intense positive selection during recent human evolution. This test also reveals that, on average, ASPM fixed one advantageous amino acid change in every 300 000-400 000 years since the human lineage diverged from chimpanzees some 5-6 million years ago. We therefore conclude that ASPM underwent strong adaptive evolution in the descent of Homo sapiens, which is consistent with its putative role in the evolutionary enlargement of the human brain.",
author = "Evans, {P D} and Anderson, {J R} and Vallender, {E J} and Gilbert, {S L} and Malcom, {C M} and S Dorus and Lahn, {B T}",
note = "ID number: ISI:000188989200002",
year = "2004",
doi = "10.1093/hmg/ddh055",
language = "English",
volume = "13",
pages = "489--494",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans

AU - Evans, P D

AU - Anderson, J R

AU - Vallender, E J

AU - Gilbert, S L

AU - Malcom, C M

AU - Dorus, S

AU - Lahn, B T

N1 - ID number: ISI:000188989200002

PY - 2004

Y1 - 2004

N2 - A prominent trend in the evolution of humans is the progressive enlargement of the cerebral cortex. The ASPM (Abnormal spindle-like microcephaly associated) gene has the potential to play a role in this evolu-tionary process, because mutations in this gene cause severe reductions in the cerebral cortical size of affected humans. Here, we show that the evolution of ASPM is significantly accelerated in great apes, especially along the ape lineages leading to humans. Additionally, the lineage from the last human/chimpanzee ancestor to humans shows an excess of non-synonymous over synonymous substitutions, which is a signature of positive Darwinian selection. A comparison of polymorphism and divergence using the McDonald-Kreitman test confirms that ASPM has indeed experienced intense positive selection during recent human evolution. This test also reveals that, on average, ASPM fixed one advantageous amino acid change in every 300 000-400 000 years since the human lineage diverged from chimpanzees some 5-6 million years ago. We therefore conclude that ASPM underwent strong adaptive evolution in the descent of Homo sapiens, which is consistent with its putative role in the evolutionary enlargement of the human brain.

AB - A prominent trend in the evolution of humans is the progressive enlargement of the cerebral cortex. The ASPM (Abnormal spindle-like microcephaly associated) gene has the potential to play a role in this evolu-tionary process, because mutations in this gene cause severe reductions in the cerebral cortical size of affected humans. Here, we show that the evolution of ASPM is significantly accelerated in great apes, especially along the ape lineages leading to humans. Additionally, the lineage from the last human/chimpanzee ancestor to humans shows an excess of non-synonymous over synonymous substitutions, which is a signature of positive Darwinian selection. A comparison of polymorphism and divergence using the McDonald-Kreitman test confirms that ASPM has indeed experienced intense positive selection during recent human evolution. This test also reveals that, on average, ASPM fixed one advantageous amino acid change in every 300 000-400 000 years since the human lineage diverged from chimpanzees some 5-6 million years ago. We therefore conclude that ASPM underwent strong adaptive evolution in the descent of Homo sapiens, which is consistent with its putative role in the evolutionary enlargement of the human brain.

UR - http://dx.doi.org/10.1093/hmg/ddh055

U2 - 10.1093/hmg/ddh055

DO - 10.1093/hmg/ddh055

M3 - Article

VL - 13

SP - 489

EP - 494

JO - Human Molecular Genetics

T2 - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 5

ER -