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Durham University

Department of Anthropology


Publication details for Professor Robert A. Barton

Montgomery, Stephen., Capellini, Isabella., Venditti, Chris., Barton, Robert. & Mundy, Nick. (2011). Adaptive Evolution of Four Microcephaly Genes and the Evolution of Brain Size in Anthropoid Primates. Molecular Biology and Evolution 28(1): 625-638.

Author(s) from Durham


The anatomical basis and adaptive function of the expansion in primate brain size have long been studied; however, we are
only beginning to understand the genetic basis of these evolutionary changes. Genes linked to human primary
microcephaly have received much attention as they have accelerated evolutionary rates along lineages leading to humans.
However, these studies focus narrowly on apes, and the link between microcephaly gene evolution and brain evolution is
disputed. We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ,
MCPH1) across 21 species representing all major clades of anthropoid primates. Contrary to prevailing assumptions,
positive selection was not limited to or intensified along the lineage leading to humans. In fact we show that all four loci
were subject to positive selection across the anthropoid primate phylogeny. We developed clearly defined hypotheses to
explicitly test if selection on these loci was associated with the evolution of brain size. We found positive relationships
between both CDK5RAP2 and ASPM and neonatal brain mass and somewhat weaker relationships between these genes
and adult brain size. In contrast, there is no evidence linking CENPJ and MCPH1 to brain size evolution. The stronger
association of ASPM and CDK5RAP2 evolution with neonatal brain size than with adult brain size is consistent with these
loci having a direct effect on prenatal neuronal proliferation. These results suggest that primate brain size may have at least
a partially conserved genetic basis. Our results contradict a previous study that linked adaptive evolution of ASPM to
changes in relative cortex size; however, our analysis indicates that this conclusion is not robust. Our finding that the
coding regions of two widely expressed loci has experienced pervasive positive selection in relation to a complex,
quantitative developmental phenotype provides a notable counterexample to the commonly asserted hypothesis that cisregulatory
regions play a dominant role in phenotypic evolution.