Precise identification of cascading alpha satellite higher order repeats in T2T-CHM13 assembly of human chromosome 3.

AIM: To precisely identify and analyze alpha-satellite higher-order repeats (HORs) in T2T-CHM13 assembly of human chromosome 3. METHODS: From the recently sequenced complete T2T-CHM13 assembly of human chromosome 3, the precise alpha satellite HOR structure was computed by using the novel high-precision GRM2023 algorithm with global repeat map (GRM) and monomer distance (MD) diagrams. RESULTS: The major alpha satellite HOR array in chromosome 3 revealed a novel cascading HOR, housing 17mer HOR copies with subfragments of periods 15 and 2. Within each row in the cascading HOR, the monomers were of different types, but different rows within the same cascading 17mer HOR contained more than one monomer of the same type. Each canonical 17mer HOR copy comprised 17 monomers belonging to 16 different monomer types. Another pronounced 10mer HOR array was of the regular Willard's type. CONCLUSION: Our findings emphasize the complexity within the chromosome 3 centromere as well as deviations from expected highly regular patterns.

Novel Concept of Alpha Satellite Cascading Higher-Order Repeats (HORs) and Precise Identification of 15mer and 20mer Cascading HORs in Complete T2T-CHM13 Assembly of Human Chromosome 15.

Unraveling the intricate centromere structure of human chromosomes holds profound implications, illuminating fundamental genetic mechanisms and potentially advancing our comprehension of genetic disorders and therapeutic interventions. This study rigorously identified and structurally analyzed alpha satellite higher-order repeats (HORs) within the centromere of human chromosome 15 in the complete T2T-CHM13 assembly using the high-precision GRM2023 algorithm. The most extensive alpha satellite HOR array in chromosome 15 reveals a novel cascading HOR, housing 429 15mer HOR copies, containing 4-, 7- and 11-monomer subfragments. Within each row of cascading HORs, all alpha satellite monomers are of distinct types, as in regular Willard's HORs. However, different HOR copies within the same cascading 15mer HOR contain more than one monomer of the same type. Each canonical 15mer HOR copy comprises 15 monomers belonging to only 9 different monomer types. Notably, 65% of the 429 15mer cascading HOR copies exhibit canonical structures, while 35% display variant configurations. Identified as the second most extensive alpha satellite HOR, another novel cascading HOR within human chromosome 15 encompasses 164 20mer HOR copies, each featuring two subfragments. Moreover, a distinct pattern emerges as interspersed 25mer/26mer structures differing from regular Willard's HORs and giving rise to a 34-monomer subfragment. Only a minor 18mer HOR array of 12 HOR copies is of the regular Willard's type. These revelations highlight the complexity within the chromosome 15 centromeric region, accentuating deviations from anticipated highly regular patterns and hinting at profound information encoding and functional potential within the human centromere.

Novel Cascade Alpha Satellite HORs in Orangutan Chromosome 13 Assembly: Discovery of the 59mer HOR-The largest Unit in Primates-And the Missing Triplet 45/27/18 HOR in Human T2T-CHM13v2.0 Assembly.

From the recent genome assembly NHGRI_mPonAbe1-v2.0_NCBI (GCF_028885655.2) of orangutan chromosome 13, we computed the precise alpha satellite higher-order repeat (HOR) structure using the novel high-precision GRM2023 algorithm with Global Repeat Map (GRM) and Monomer Distance (MD) diagrams. This study rigorously identified alpha satellite HORs in the centromere of orangutan chromosome 13, discovering a novel 59mer HOR-the longest HOR unit identified in any primate to date. Additionally, it revealed the first intertwined sequence of three HORs, 18mer/27mer/45mer HORs, with a common aligned "backbone" across all HOR copies. The major 7mer HOR exhibits a Willard's-type canonical copy, although some segments of the array display significant irregularities. In contrast, the 14mer HOR forms a regular Willard's-type HOR array. Surprisingly, the GRM2023 high-precision analysis of chromosome 13 of human genome assembly T2T-CHM13v2.0 reveals the presence of only a 7mer HOR, despite both the orangutan and human genome assemblies being derived from whole genome shotgun sequences.

The Supersymmetry Genetic Code Table and Quadruplet Symmetries of DNA Molecules Are Unchangeable and Synchronized with Codon-Free Energy Mapping during Evolution.

The Supersymmetry Genetic code (SSyGC) table is based on five physicochemical symmetries: (1) double mirror symmetry on the principle of the horizontal and vertical mirror symmetry axis between all bases (purines [A, G) and pyrimidines (U, C)] and (2) of bases in the form of codons; (3) direct-complement like codon/anticodon symmetry in the sixteen alternating boxes of the genetic code columns; (4) A + T-rich and C + G-rich alternate codons in the same row between both columns of the genetic code; (5) the same position between divided and undivided codon boxes in relation to horizontal mirror symmetry axis. The SSyGC table has a unique physicochemical purine-pyrimidine symmetry net which is as the core symmetry common for all, with more than thirty different nuclear and mitochondrial genetic codes. This net is present in the SSyGC table of all RNA and DNA living species. None of these symmetries are present in the Standard Genetic Code (SGC) table which is constructed on the alphabetic horizontal and vertical U-C-A-G order of bases. Here, we show that the free energy value of each codon incorporated as fundamentally mapping the "energy code" in the SSyGC table is compatible with mirror symmetry. On the other hand, in the SGC table, the same free energy values of codons are dispersed and a mirror symmetry between them is not recognizable. At the same time, the mirror symmetry of the SSyGC table and the DNA quadruplets together with our classification of codons/trinucleotides are perfectly imbedded in the mirror symmetry energy mapping of codons/trinucleotides and point out in favor of maintaining the integrity of the genetic code and DNA genome. We also argue that physicochemical symmetries of the SSyGC table in the manner of the purine-pyrimidine symmetry net, the quadruplet symmetry of DNA molecule, and the free energy of codons have remined unchanged during all of evolution. The unchangeable and universal symmetry properties of the genetic code, DNA molecules, and the energy code are decreasing disorder between codons/trinucleotides and shed a new light on evolution. Diversity in all living species on Earth is broad, but the symmetries of the Supersymmetry Genetic Code as the code of life and the DNA quadruplets related to the "energy code" are unique, unchangeable, and have the power of natural laws.