GC-biased gene conversion (gBGC) is a recombination-associated evolutionary 
process that accelerates the fixation of guanine or cytosine alleles, regardless 
of their effects on fitness. gBGC can increase the overall rate of 
substitutions, a hallmark of positive selection. Many fast-evolving genes and 
noncoding sequences in the human genome have GC-biased substitution patterns, 
suggesting that gBGC-in contrast to adaptive processes-may have driven the human 
changes in these sequences. To investigate this hypothesis, we developed a 
substitution model for DNA sequence evolution that quantifies the nonlinear 
interacting effects of selection and gBGC on substitution rates and patterns. 
Based on this model, we used a series of lineage-specific likelihood ratio tests 
to evaluate sequence alignments for evidence of changes in mode of selection, 
action of gBGC, or both. With a false positive rate of less than 5% for 
individual tests, we found that the majority (76%) of previously identified 
human accelerated regions are best explained without gBGC, whereas a substantial 
minority (19%) are best explained by the action of gBGC alone. Further, more 
than half (55%) have substitution rates that significantly exceed local 
estimates of the neutral rate, suggesting that these regions may have been 
shaped by positive selection rather than by relaxation of constraint. By 
distinguishing the effects of gBGC, relaxation of constraint, and positive 
selection we provide an integrated analysis of the evolutionary forces that 
shaped the fastest evolving regions of the human genome, which facilitates the 
design of targeted functional studies of adaptation in humans.