INTERHOMOLOGUE SEQUENCE VARIATION OF ALPHA-SATELLITE DNA FROM HUMAN-CHROMOSOME-17 - EVIDENCE FOR CONCERTED EVOLUTION ALONG HAPLOTYPIC LINEAGES

Alpha satellite DNA is a family of tandemly repeated DNA found at the centromeres of all primate chromosomes. Different human chromosomes 17 in the population are characterized by distinct alpha satellite haplo types, distinguished by the presence of variant repeat forms that have precise monomeric deletions. Pairwise comparisons of sequence diversi ty between variant repeat units from each haplotype show that they are closely related in sequence. Direct sequencing of PCR-amplified alpha satellite reveals heterogeneous positions between the repeat units on a chromosome as two bands at the same position on a sequencing ladder . No variation was detected in the sequence and location of these hete rogeneous positions between chromosomes 17 from the same haplotype, bu t distinct patterns of variation were detected between chromosomes fro m different haplotypes. Subsequent sequence analysis of individual rep eats from each haplotype confirmed the presence of extensive haplotype -specific sequence variation. Phylogenetic inference yielded a tree th at suggests these chromosome 17 repeat units evolve principally along haplotypic lineages. These studies allow insight into the relative rat es and/or timing of genetic turnover processes that lead to the homoge nization of tandem DNA families.