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Advances in Bioinformatics
Volume 2010 (2010), Article ID 856825, 7 pages
Research Article

Adaptive Evolution Hotspots at the GC-Extremes of the Human Genome: Evidence for Two Functionally Distinct Pathways of Positive Selection

1Laboratory of Computational Oncology, Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
2Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam Rd, Pokfulam, Hong Kong

Received 25 August 2009; Revised 31 December 2009; Accepted 10 February 2010

Academic Editor: Igor B. Rogozin

Copyright © 2010 Clara S. M. Tang and Richard J. Epstein. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We recently reported that the human genome is ‘‘splitting’’ into two gene subgroups characterised by polarised GC content (Tang et al, 2007), and that such evolutionary change may be accelerated by programmed genetic instability (Zhao et al, 2008). Here we extend this work by mapping the presence of two separate high-evolutionary-rate (Ka/Ks) hotspots in the human genome—one characterized by low GC content, high intron length, and low gene expression, and the other by high GC content, high exon number, and high gene expression. This finding suggests that at least two different mechanisms mediate adaptive genetic evolution in higher organisms: (1) intron lengthening and reduced repair in hypermethylated lowly-transcribed genes, and (2) duplication and/or insertion events affecting highly-transcribed genes, creating low-essentiality satellite daughter genes in nearby regions of active chromatin. Since the latter mechanism is expected to be far more efficient than the former in generating variant genes that increase fitnesss, these results also provide a potential explanation for the controversial value of sequence analysis in defining positively selected genes.