Tandem NBPF 3mer HORs (Olduvai triplets) in Neanderthal and two novel HOR tandem arrays in human chromosome 1 T2T-CHM13 assembly

Abstract

It is known that the ~ 1.6 kb Neuroblastoma BreakPoint Family (NBPF) repeats are human specific and contributing to cognitive capabilities, with increasing frequency in higher order repeat 3mer HORs (Olduvai triplets). From chimpanzee to modern human there is a discontinuous jump from 0 to ~ 50 tandemly organized 3mer HORs. Here we investigate the structure of NBPF 3mer HORs in the Neanderthal genome assembly of Pääbo et al., comparing it to the results obtained for human hg38.p14 chromosome 1. Our findings reveal corresponding NBPF 3mer HOR arrays in Neanderthals with slightly different monomer structures and numbers of HOR copies compared to humans. Additionally, we compute the NBPF 3mer HOR pattern for the complete telomere-to-telomere human genome assembly (T2T-CHM13) by Miga et al., identifying two novel tandem arrays of NBPF 3mer HOR repeats with 5 and 9 NBPF 3mer HOR copies. We hypothesize that these arrays correspond to novel NBPF genes (here referred to as NBPFA1 and NBPFA2). Further improving the quality of the Neanderthal genome using T2T-CHM13 as a reference would be of great interest in determining the presence of such distant novel NBPF genes in the Neanderthal genome and enhancing our understanding of human evolution.

Figure 1

Maps of gaps, NBPF gene members, and their content of Olduvai repeats in the human chromosome 1 genome hg38 assembly. (a) Positions of gaps (blue rectangles) (indicated in the assembly as ‘N’s) larger than 2000 bp. (b) Positions of NBPF gene members (red rectangles) (according to the National Center for Biotechnology Information) and arrangement of Olduvai domain subtypes. Only HLS1 (1), HLS2 (2), and HLS3 (3) Olduvai domains subtypes are indicated. Domains consisting of two different HLS types are denoted with two connected numbers (e.g., the second domain in NBPF26 consists of half HLS2 and half HLS1, is indicated as 21). It is evident that the hg38 assembly has a gap at the position of the NBPF1 and NBPF7P genes.

Figure 2

GRM diagrams for 140–150 Mb segment of chromosome 1: (a) Chimpanzee NHGRI_mPanTro3-v1.1; (b) Neanderthal AltaiNea.hg19, and (c) Complete human T2T CHM13 assembly. GRM diagrams have pronounced GRM peaks at ~ 4.8 kb for Neanderthal and human genomes, while for chimpanzee the peak at ~ 4.8 kb is absent.

Figure 3

Comparison of NBPF monomer alignment scheme for NBPF 3mer HOR copies for chromosome 1 in chimpanzee NHGRI_mPanTro3-v1.1 (1st panel), Neanderthal AltaiNea.hg19 (2nd panel), human hg38.p14 (3rd panel) and complete human T2T-CHM13 (4th panel). Boxes represent three types of NBPF monomers, denoted m1 (orange), m2 (light blue) and m3 (blue). Each row of boxes (three in canonical HOR copy, two or one in variant HOR copies) represents an NBPF HOR copy. In front of each row (HOR copy) its start position in the genomic sequence is given. Initial positions that are in bold indicate monomers that appear in the original sequence in the reverse-complement orientation. Each array of tandemly arranged HOR copies is separated from neighboring arrays and/or isolated individual monomers by blank space. Consensus monomers determined by GRM algorithm for human and Neanderthal genome are almost the same (average divergence less than 4%). A characteristics of chimpanzee NHGRI_mPanTro3-v1.1 assembly is the absence of canonical HOR copies. Moreover, except in the second variant HOR copy m1m3 (at position 21,523,475 bp), the m3 NBPF monomer is missing. A pronounced additional segment, identified only for the T2T-CHM13 assembly, is the appearance of two novel tandem arrays of NBPF 3mer HOR copies, the 5-copy and 9-copy arrays, interpreted as belonging to the novel genes named NBPFA1 and NBPFA2 genes.