Ines Vlahović

Intragene Higher Order Repeats in Neuroblastoma BreakPoint Family Genes Distinguish Humans from Chimpanzees

Much attention has been devoted to identifying genomic patterns underlying the evolution of the human brain and its emergent advanced cognitive capabilities, which lie at the heart of differences distinguishing humans from chimpanzees, our closest living relatives. Here, we identify two particular intragene repeat structures of noncoding human DNA, spanning as much as a hundred kilobases, that are present in human genome but are absent from the chimpanzee genome and other nonhuman primates. Using our novel computational method Global Repeat Map, we examine tandem repeat structure in human and chimpanzee chromosome 1. In human chromosome 1, we find three higher order repeats (HORs), two of them novel, not reported previously, whereas in chimpanzee chromosome 1, we find only one HOR, a 2mer alphoid HOR instead of human alphoid 11mer HOR. In human chromosome 1, we identify an HOR based on 39-bp primary repeat unit, with secondary, tertiary, and quartic repeat units, fully embedded in human hornerin gene, related to regenerating and psoriatric skin. Such an HOR is not found in chimpanzee chromosome 1. We find a remarkable human 3mer HOR organization based on the ~1.6-kb primary repeat unit, fully embedded within the neuroblastoma breakpoint family genes, which is related to the function of the human brain. Such HORs are not present in chimpanzees. In general, we find that human-chimpanzee differences are much larger for tandem repeats, in particularly for HORs, than for gene sequences. This may be of great significance in light of recent studies that are beginning to reveal the large-scale regulatory architecture of the human genome, in particular the role of noncoding sequences. We hypothesize about the possible importance of human accelerated HOR patterns as components in the gene expression multilayered regulatory network.

Regular higher order repeat structures in beetle Tribolium castaneum genome

Abstract Higher order repeats (HORs) containing tandems of primary and secondary repeat units (head-to-tail “tandem within tandem pattern”), referred to as regular HORs, are typical for primate alpha satellite DNAs and most pronounced in human genome. Regular HORs are known to be a result of recent evolutionary processes. In non-primate genomes mostly so called complex HORs have been found, without head to tail tandem of primary repeat units. In beetle Tribolium castaneum, considered as a model case for genome studies, large tandem repeats have been identified, but no HORs have been reported. Here, using our novel robust repeat finding algorithm Global Repeat Map, we discover two regular and six complex HORs in T. castaneum. In organizational pattern, the integrity and homogeneity of regular HORs in T. castaneum resemble human regular HORs (with T. castaneum monomers different from human alpha satellite monomers), involving a wider range of monomer lengths than in human HORs. Similar regular higher order repeat structures have previously not been found in insects. Some of these novel HORs in T. castaneum appear as most regular among known HORs in non-primate genomes, although with substantial riddling. This is intriguing, in particular from the point of view of role of non-coding repeats in modulation of gene expression.

Trinucleotide’s quadruplet symmetries and natural symmetry law of DNA creation ensuing Chargaff’s second parity rule

For almost 50 years the conclusive explanation of Chargaff’s second parity rule (CSPR), the equality of frequencies of nucleotides A=T and C=G or the equality of direct and reverse complement trinucleotides in the same DNA strand, has not been determined yet. Here, we relate CSPR to the interstrand mirror symmetry in 20 symbolic quadruplets of trinucleotides (direct, reverse complement, complement, and reverse) mapped to double-stranded genome. The symmetries of Q-box corresponding to quadruplets can be obtained as a consequence of Watson–Crick base pairing and CSPR together. Alternatively, assuming Natural symmetry law for DNA creation that each trinucleotide in one strand of DNA must simultaneously appear also in the opposite strand automatically leads to Q-box direct-reverse mirror symmetry which in conjunction with Watson–Crick base pairing generates CSPR. We demonstrate quadruplet’s symmetries in chromosomes of wide range of organisms, from Escherichia coli to Neanderthal and human genomes, introducing novel quadruplet-frequency histograms and 3D-diagrams with combined interstrand frequencies. These “landscapes” are mutually similar in all mammals, including extinct Neanderthals, and somewhat different in most of older species. In human chromosomes 1–12, and X, Y the “landscapes” are almost identical and slightly different in the remaining smaller and telocentric chromosomes. Quadruplet frequencies could provide a new robust tool for characterization and classification of genomes and their evolutionary trajectories.