NONRANDOM LOCALIZATION OF RECOMBINATION EVENTS IN HUMAN ALPHA-SATELLITE REPEAT UNIT VARIANTS - IMPLICATIONS FOR HIGHER-ORDER STRUCTURAL CHARACTERISTICS WITHIN CENTROMERIC HETEROCHROMATIN

Tandemly repeated DNA families appear to undergo concerted evolution, such that repeat units within a species have a higher degree of sequen ce similarity than repeat units from even closely related species. Whi le intraspecies homogenization of repeat units can be explained satisf actorily by repeated rounds of genetic exchange processes such as uneq ual crossing over and/or gene conversion, the parameters controlling t hese processes remain largely unknown. Alpha satellite DNA is a noncod ing tandemly repeated DNA family found at the centromeres of all human and primate chromosomes. We have used sequence analysis to investigat e the molecular basis of 13 variant alpha satellite repeat units, allo wing comparison of multiple independent recombination events in closel y related DNA sequences. The distribution of these events within the 1 71-bp monomer is nonrandom and clusters in a distinct 20- to 25-bp reg ion, suggesting possible effects of primary sequence and/or chromatin structure. The position of these recombination events may be associate d with the location within the higher-order repeat unit of the binding site for the centromere-specific protein CENP-B. These studies have i mplications for the molecular nature of genetic recombination, mechani sms of concerted evolution, and higher-order structure of centromeric heterochromatin.