| Abstract: | Sequence analysis of alphoid repeats from human chromosomes 17, 21 and 13 reveals recurrent diagnostic variant nucleotides. Their combinations define haplotypes, with higher order repeats (HORs) containing identical or closely-related haplotypes tandemly arranged into separate domains. The haplotypes found on homologues can be totally different, while HORs remain 99.8% homogeneous both intrachromosomally and between homologues. These results support the hypothesis, never before demonstrated, that unequal crossovers between sister chromatids accumulate to produce homogenization and amplification into tandem alphoid repeats. I propose that the molecular basis of this involves the diagnostic variant nucleotides, which enable pairing between HORs with identical or closely-related haplotypes. Domains are thus periodically renewed to maintain high intrachromosomal and interhomologue homogeneity. The capacity of a domain to form an active centromere is maintained as long as neither retrotransposons nor significant numbers of mutations affect it. In the presented model, a chromosome with an altered centromere can be transiently rescued by forming a neocentromere, until a restored, fully-competent domain is amplified de novo or rehomogenized through the accumulation of unequal crossovers. |
