Large Tandem, Higher Order Repeats and Regularly Dispersed Repeat Units Contribute Substantially to Divergence Between Human and Chimpanzee Y Chromosomes

Abstract

Comparison of human and chimpanzee genomes has received much attention, because of paramount role for understanding evolutionary step distinguishing us from our closest living relative. In order to contribute to insight into Y chromosome evolutionary history, we study and compare tandems, higher order repeats (HORs), and regularly dispersed repeats in human and chimpanzee Y chromosome contigs, using robust Global Repeat Map algorithm. We find a new type of long-range acceleration, human-accelerated HOR regions. In peripheral domains of 35mer human alphoid HORs, we find riddled features with ten additional repeat monomers. In chimpanzee, we identify 30mer alphoid HOR. We construct alphoid HOR schemes showing significant human-chimpanzee difference, revealing rapid evolution after human-chimpanzee separation. We identify and analyze over 20 large repeat units, most of them reported here for the first time as: chimpanzee and human ∼1.6 kb 3mer secondary repeat unit (SRU) and ∼23.5 kb tertiary repeat unit (∼0.55 kb primary repeat unit, PRU); human 10848, 15775, 20309, 60910, and 72140 bp PRUs; human 3mer SRU (∼2.4 kb PRU); 715mer and 1123mer SRUs (5mer PRU); chimpanzee 5096, 10762, 10853, 60523 bp PRUs; and chimpanzee 64624 bp SRU (10853 bp PRU). We show that substantial human-chimpanzee differences are concentrated in large repeat structures, at the level of as much as ∼70% divergence, sizably exceeding previous numerical estimates for some selected noncoding sequences. Smeared over the whole sequenced assembly (25 Mb) this gives ∼14% human-chimpanzee divergence. This is significantly higher estimate of divergence between human and chimpanzee than previous estimates.

Start/stop Codon-like Trinucleotides (CLTs) and Extended Clusters as New Language of DNA

“…The stop-TAA CLT has a significant extension, but is of very low frequency. On the other hand, the extension of stop-TAG CLT is sizably larger in some non-alpha satellite HORs, which have primary repeat units of 1.6, 2.4, and 0.55 kb 32,33 sizably larger than alpha satellites (~0.171 kb).…”

“…As a case study, this new method is applied to the following DNA sequences: to human and chim-panzee alpha satellite consensus HORs, to monomeric alpha satellite regions and to no-repeat DNA regions (Table 1 and Supplementary table S1). In these studies the consensus sequences are determined by GRM analysis [25][26][27][28][29][30][31][32][33] of the recent Build 37.2 assembly (Figure 1). First the dinucleotide frequencies in consensus alpha satellites are analyzed (Supplementary table S2).…”

“…Identification and analysis of repeats and HORs and their consensus sequences is performed using the GRM (Global Repeat Map) algorithm [31][32][33] applied to the Build 37.2 and Build 2.2 assemblies of human and chimpanzee genomic sequences, respectively. GRM gives a direct mapping of symbolic DNA sequences into frequency domain providing a global map of repeats.…”

Direct mapping of symbolic DNA sequence into frequency domain in global repeat map algorithm

“…We reproduced previously known repeats, and in addition we discovered a dozen of novel repeats (78,79). In this article we extend the software of GRM algorithm (new source code www.hazu.hr/grm/tools.html#grm2012) to be able to treat as large genomic sequences as hundreds of megabases and we formulate this model in a general framework incorporating crucial elements from both the digital signal processing and the string matching approaches.…”

Global Repeat Map Method for Higher Order Repeat Alpha Satellites in Human and Chimpanzee Genomes (Build 37.2 Assembly)

“…50 It is very unlikely that the 17mer unit arose from 13mer unit by addition of four monomers, because monomers alignment excluded possibility that the four additional monomers in 17mer unit are duplications of any monomers from 13mer unit (see chromosome 19 13mer and 17mer alignment in a heatmap from Figure 9). Therefore, we hypothesized that the shorter, 13mer higher-order repeat unit arose from the longer 17mer higher-order unit by deletion of four alpha satellite monomers which are all distinct from the monomers in 13mer.…”