Abstract
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.
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Acknowledgments
Helpful comments from A. Marín, J.P. Martínez-Camacho, M. Ruiz-Rejón, and two anonymous reviewers are greatly appreciated. We are also grateful to A. Smit for providing the RepeatMasker computer program. This work was supported by the Spanish Government (Grants BIO2002-04014-C03-01/02 to J.L.O. and P.B. and BFM2002-00183 to P.C. and P.B.) and Plan Andaluz de Investigacion (CVI-162). M.H. acknowledges a predoctoral grant from the University of Granada (Spain). The help of David Nesbitt and Christopher Previti with the English version of the manuscript is also appreciated.
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Hackenberg, M., Bernaola-Galván, P., Carpena, P. et al. The Biased Distribution of Alus in Human Isochores Might Be Driven by Recombination. J Mol Evol 60, 365–377 (2005). https://doi.org/10.1007/s00239-004-0197-2
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DOI: https://doi.org/10.1007/s00239-004-0197-2