Abstract
Alpha satellite domains that currently function as centromeres of human chromosomes are flanked by layers of older alpha satellite, thought to contain dead centromeres of primate progenitors, which lost their function and the ability to homogenize satellite repeats, upon appearance of a new centromere. Using cladistic analysis of alpha satellite monomers, we elucidated complete layer patterns on chromosomes 8, 17, and X and related them to each other and to primate alpha satellites. We show that discrete and chronologically ordered alpha satellite layers are partially symmetrical around an active centromere and their succession is partially shared in non-homologous chromosomes. The layer structure forms a visual representation of the human evolutionary lineage with layers corresponding to ancestors of living primates and to entirely fossil taxa. Surprisingly, phylogenetic comparisons suggest that alpha satellite arrays went through periods of unusual hypermutability after they became “dead” centromeres. The layer structure supports a model of centromere evolution where new variants of a satellite repeat expanded periodically in the genome by rounds of inter-chromosomal transfer/amplification. Each wave of expansion covered all or many chromosomes and corresponded to a new primate taxon. Complete elucidation of the alpha satellite phylogenetic record would give a unique opportunity to number and locate the positions of major extinct taxa in relation to human ancestors shared with extant primates. If applicable to other satellites in non-primate taxa, analysis of centromeric layers could become an invaluable tool for phylogenetic studies.
Highlights
Active human centromeres are made of great ape-specific alpha satellite DNA (AS), comprised of,171 bp tandem monomers forming nearly identical higher order repeats (HORs) and represented by the ‘‘new’’ suprachromosomal families (SFs) 1, 2 and 3
R2 is similar to M1, and R1 represents the first appearance of novel class B monomers, which bind CENP-B protein and presumably have invaded the A-arrays before the great ape divergence [1]
The expanding centromere model poses two main questions: (1) whether the succession of layers is symmetrical on both sides of the centromere, and (2) whether different chromosomes share the same layers
Summary
Active human centromeres are made of great ape-specific alpha satellite DNA (AS), comprised of ,171 bp tandem monomers forming nearly identical higher order repeats (HORs) and represented by the ‘‘new’’ suprachromosomal families (SFs) 1, 2 and 3. They are surrounded by much less homogeneous HOR-free ‘‘monomeric’’ AS (SF4 and SF5) often disrupted by transposon insertions [1,2]. Analysis of the human X chromosome short arm (Xp) pericentromeric region, the first one sequenced in its entirety, has revealed an age gradient, with most distal Xp AS domain dating to early primate evolution, the HOR domain to the time of great ape divergence and the domains in between being of interim age [3,4]. Assuming that the succession of AS layers on the long arm (Xq) side is symmetrical, it was proposed that the primate X chromosome centromere ‘‘evolved through repeated expansion events involving the central functional AS domain, such that ancestral centromeric sequences were split and displaced distally onto each arm’’ [4]
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