Human Genetics

, Volume 119, Issue 1, pp 169–178

Human-specific nonsense mutations identified by genome sequence comparisons

Original Investigation

DOI: 10.1007/s00439-005-0125-6

Cite this article as:
Hahn, Y. & Lee, B. Hum Genet (2006) 119: 169. doi:10.1007/s00439-005-0125-6


The comparative study of the human and chimpanzee genomes may shed light on the genetic ingredients for the evolution of the unique traits of humans. Here, we present a simple procedure to identify human-specific nonsense mutations that might have arisen since the human–chimpanzee divergence. The procedure involves collecting orthologous sequences in which a stop codon of the human sequence is aligned to a non-stop codon in the chimpanzee sequence and verifying that the latter is ancestral by finding homologs in other species without a stop codon. Using this procedure, we identify nine genes (CML2, FLJ14640, MT1L, NPPA, PDE3B, SERPINA13, TAP2, UIP1, and ZNF277) that would produce human-specific truncated proteins resulting in a loss or modification of the function. The premature terminations of CML2, MT1L, and SERPINA13 genes appear to abolish the original function of the encoded protein because the mutation removes a major part of the known active site in each case. The other six mutated genes are either known or presumed to produce functionally modified proteins. The mutations of five genes (CML2, FLJ14640, MT1L, NPPA, TAP2) are known or predicted to be polymorphic in humans. In these cases, the stop codon alleles are more prevalent than the ancestral allele, suggesting that the mutant alleles are approaching fixation since their emergence during the human evolution. The findings support the notion that functional modification or inactivation of genes by nonsense mutation is a part of the process of adaptive evolution and acquisition of species-specific features.


Nonsense mutation Human Chimpanzee Molecular evolution 

Supplementary material

439_2005_125_MOESM1_ESM.pdf (510 kb)
Supplementary material

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Laboratory of Molecular Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA

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