Alu retrotransposons do not show a homogeneous distribution over the human 
genome but have a higher density in GC-rich (H) than in AT-rich (L) isochores. 
However, since they preferentially insert into the L isochores, the question 
arises: What is the evolutionary mechanism that shifts the Alu density maximum 
from L to H isochores? To disclose the role played by each of the potential 
mechanisms involved in such biased distribution, we carried out a genome-wide 
analysis of the density of the Alus as a function of their evolutionary age, 
isochore membership, and intron vs. intergene location. Since Alus depend on the 
retrotransposase encoded by the LINE1 elements, we also studied the distribution 
of LINE1 to provide a complete evolutionary scenario. We consecutively check, 
and discard, the contributions of the Alu/LINE1 competition for 
retrotransposase, compositional matching pressure, and Alu overrepresentation in 
introns. In analyzing the role played by unequal recombination, we scan the 
genome for Alu trimers, a direct product of Alu-Alu recombination. Through 
computer simulations, we show that such trimers are much more frequent than 
expected, the observed/expected ratio being higher in L than in H isochores. 
This result, together with the known higher selective disadvantage of 
recombination products in H isochores, points to Alu-Alu recombination as the 
main agent provoking the density shift of Alus toward the GC-rich parts of the 
genome. Two independent pieces of evidence-the lower evolutionary divergence 
shown by recently inserted Alu subfamilies and the higher frequency of old 
stand-alone Alus in L isochores-support such a conclusion. Other evolutionary 
factors, such as population bottlenecks during primate speciation, may have 
accelerated the fast accumulation of Alus in GC-rich isochores.