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Open Access Highly Accessed Open Badges Methodology article

Patterns of evolutionary constraints on genes in humans

Subhajyoti De1*, Nuria Lopez-Bigas2 and Sarah A Teichmann1*

Author Affiliations

1 MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

2 Research Unit on Biomedical Informatics, Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain

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BMC Evolutionary Biology 2008, 8:275  doi:10.1186/1471-2148-8-275

Published: 7 October 2008



Different regions in a genome evolve at different rates depending on structural and functional constraints. Some genomic regions are highly conserved during metazoan evolution, while other regions may evolve rapidly, either in all species or in a lineage-specific manner. A strong or even moderate change in constraints in functional regions, for example in coding regions, can have significant evolutionary consequences.


Here we discuss a novel framework, 'BaseDiver', to classify groups of genes in humans based on the patterns of evolutionary constraints on polymorphic positions in their coding regions. Comparing the nucleotide-level divergence among mammals with the extent of deviation from the ancestral base in the human lineage, we identify patterns of evolutionary pressure on nonsynonymous base-positions in groups of genes belonging to the same functional category. Focussing on groups of genes in functional categories, we find that transcription factors contain a significant excess of nonsynonymous base-positions that are conserved in other mammals but changed in human, while immunity related genes harbour mutations at base-positions that evolve rapidly in all mammals including humans due to strong preference for advantageous alleles. Genes involved in olfaction also evolve rapidly in all mammals, and in humans this appears to be due to weak negative selection.


While recent studies have identified genes under positive selection in humans, our approach identifies evolutionary constraints on Gene Ontology groups identifying changes in humans relative to some of the other mammals.