Genomic Characterization of Large Heterochromatic Gaps in the Human Genome Assembly
The most abundant human satellites are alphoid sequences and simple sequence satellites (satellite 2 and 3). Alphoid sequences are now regarded as the DNA component of the centromere and have therefore attracted most attention, leaving satellite 2 and 3 in outer darkness. The classical satellite definition stems from the characterisation of the most abundant repeat family of density gradient fractions. This definition has been reviewed in the light of recent publications. Satellite 2 and 3 sequences and organisation are clearly distinct. Satellite 3 shows a strict periodicity of 5 bp, and satellite 2 is built from two related units of 23 and 26 bp. The distinctive behaviour of satellite-2-containing regions in genetic alterations of cytosine methylation suggests that these two tandemly repeated families participate in distinct heterochromatin organisations, and that variations in satellite sequences at many separate position in the genome may be caused by alterations of heterochromatin-associated proteins. Restriction enzyme analysis indicates that satellite 2 and 3 arrays contain regularly spaced sequence alterations creating a restriction site. This homogeneity contrasts with the scattering of numerous variant sequences all over the length of the higher-order unit, and suggests that two distinct molecular processes are the cause of local variant scattering and higher-order regular homogeneity. Higher-order homogeneity reflects paradoxically a local alterations of homogeneity. Since fixation of mutations by unequal crossovers is very efficient only in small arrays, sequence replacement by biased gene conversion must explain homogeneity in the larger arrays.