Open Access Primary research

Cross-comparison of the genome sequences from human, chimpanzee, Neanderthal and a Denisovan hominin identifies novel potentially compensated mutations

Guojie Zhang1*, Zhang Pei1, Edward V Ball2, Matthew Mort2, Hildegard Kehrer-Sawatzki3 and David N Cooper2

Author Affiliations

1 Bioinformatics Department, Beijing Genomics Institute at Shenzhen, Shenzhen 518083, China

2 Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK

3 Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany

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Human Genomics 2011, 5:453-484  doi:10.1186/1479-7364-5-5-453

Published: 1 July 2011


The recent publication of the draft genome sequences of the Neanderthal and a ~50,000-year-old archaic hominin from Denisova Cave in southern Siberia has ushered in a new age in molecular archaeology. We previously cross-compared the human, chimpanzee and Neanderthal genome sequences with respect to a set of disease-causing/disease-associated missense and regulatory mutations (Human Gene Mutation Database) and succeeded in identifying genetic variants which, although apparently pathogenic in humans, may represent a 'compensated' wild-type state in at least one of the other two species. Here, in an attempt to identify further 'potentially compensated mutations' (PCMs) of interest, we have compared our dataset of disease-causing/disease-associated mutations with their corresponding nucleotide positions in the Denisovan hominin, Neanderthal and chimpanzee genomes. Of the 15 human putatively disease-causing mutations that were found to be compensated in chimpanzee, Denisovan or Neanderthal, only a solitary F5 variant (Val1736Met) was specific to the Denisovan. In humans, this missense mutation is associated with activated protein C resistance and an increased risk of thromboembolism and recurrent miscarriage. It is unclear at this juncture whether this variant was indeed a PCM in the Denisovan or whether it could instead have been associated with disease in this ancient hominin.

Human; chimpanzee; Neanderthal; Denisovan hominin; genome sequence; potentially compensated mutations; disease