The Evolutionary Origin of Man Can Be Traced in the Layers of Defunct Ancestral Alpha Satellites Flanking the Active Centromeres of Human Chromosomes

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.

Clusters of alpha satellite on human chromosome 21 are dispersed far onto the short arm and lack ancient layers

“…This model for AS evolution is supported by studies of the detailed organization of AS clusters on chromosomes X, 8 and 17 (Schueler et al 2001, Schueler et al 2005, Rudd et al 2006, Shepelev et al 2009). In all cases the HOR-containing functional centromere is surrounded by multiple monomeric AS clusters arrayed roughly symmetrically on both chromosome arms.…”

“…The actual functional centromere consists of monomers arranged in multimeric higher-order repeat (HOR) units which themselves repeat to form an array of homogenous HORs which can be megabases in length (Rudd & Willard 2004). The pericentromeric regions of chromosomes contain multiple layers of highly heterogeneous "monomeric" AS repeat arrays that lack any HOR, are composed of monomers or dimers of AS basic units, and are often found interspersed with other sequences (Rudd & Willard 2004, Shepelev et al 2009). The HOR arrays are more recently evolved than the monomeric AS clusters which are more similar to the AS of lower primates and presumably represent the remnants of earlier primate centromeres (Alexandrov et.…”

“…They are called dead AS layers and are color-coded (Table 1, Shepelev et al 2009). These layers can be discriminated by a number of structural features and ultimately through full-scale phylogenetic analysis (Shepelev et al 2009).…”

“…They are called dead AS layers and are color-coded (Table 1, Shepelev et al 2009). These layers can be discriminated by a number of structural features and ultimately through full-scale phylogenetic analysis (Shepelev et al 2009). In this paper, we refer to the old SF4 as the umbrella group named "SF4+", which includes the yellow layer and all the older layers of Shepelev et al (2009).…”

“…The sequence homogeneity of the new HOR clusters in the functional centromeres is thought to be maintained by recombination mechanisms like unequal crossover (Smith 1976) and gene conversion, while older clusters are not maintained by such events, and have accumulated mutations, transposon insertions and other rearrangements, eventually drifting into a highly divergent state (Alexandrov et al 2001, Shepelev et al 2009). …”