Selective intra-dinucleotide interactions and periodicities of bases separated by K sites: a new vision and tool for phylogeny analyses

Abstract

Direct tests of the random or non-random distribution of nucleotides on genomes have been devised to test the hypothesis of neutral, nearly-neutral or selective evolution. These tests are based on the direct base distribution and are independent of the functional (coding or non-coding) or structural (repeated or unique sequences) properties of the DNA. The first approach described the longitudinal distribution of bases in tandem repeats under the Bose–Einstein statistics. A huge deviation from randomness was found. A second approach was the study of the base distribution within dinucleotides whose bases were separated by 0, 1, 2… K nucleotides. Again an enormous difference from the random distribution was found with significances out of tables and programs. These test values were periodical and included the 16 dinucleotides. For example a high “positive” (more observed than expected dinucleotides) value, found in dinucleotides whose bases were separated by (3K + 2) sites, was preceded by two smaller “negative” (less observed than expected dinucleotides) values, whose bases were separated by (3K) or (3K + 1) sites. We examined mtDNAs, prokaryote genomes and some eukaryote chromosomes and found that the significant non-random interactions and periodicities were present up to 1000 or more sites of base separation and in human chromosome 21 until separations of more than 10 millions sites. Each nucleotide has its own significant value of its distance to neutrality; this yields 16 hierarchical significances. A three dimensional table with the number of sites of separation between the bases and the 16 significances (the third dimension is the dinucleotide, individual or taxon involved) gives directly an evolutionary state of the analyzed genome that can be used to obtain phylogenies. An example is provided.

Differences in selective profiles among single or double stranded DNA or RNA viruses. Statistical detection of its double or single stranded condition

“…Distances to neutrality resulted enormous. The significance at the 0.05 level for χ 2 1 corresponds to 3.84; I found 377.3 (see Table 1) in Sars-Cov-2 virus, for dinucleotide CG, with separation 0 (contiguous bases); the probability (P) is out of tables and programs; with Gaussian approximation (5), P < 10 -50 . The significance at the 0.05 level for χ 2 9 corresponds to 16.9; I found in human chromosome 21 χ 2 9 = 1,885,266.8 (5) for Sep 0 (P < 10 -222,180 ).…”

“…Searching for a measure of the distance to neutrality of genomes, I developed a test, based on the distance to neutrality of dinucleotides whose bases are separated by 0, 1, 2, … K nucleotide sites (1)(2)(3)(4)(5). I used as the measure of the distance to neutrality a chi-square (χ 2 ) test of the random distribution of the first base according to the second base of the dinucleotides (1)(2)(3)(4)(5).…”

“…Unexpectedly I found periodicity with period 3 in the χ 2 value of distance to neutrality in virus and prokaryotes and period 2 and 6 in human chromosomes. This periodicity of the distance to neutrality is incompatible with neutral and nearly neutral evolution (2–5).…”

Distancia al azar de dinucleótidos y diseño inteligente generalizado.

“…La discusión entre la teoría sintética de la evolución (agregando la epigenética, evolución puntuada, simbiogenésis etc.) y la teoría neutral más la casi neutral de la evolución también parece ser un debate sin término ya que se utilizan conceptos sin fundamento en la realidad o no demostrados como fijación neutral, destino de alelos, pan-selección y otros [3][4][5][6]. Por este motivo decidí estudiar la evolución selectiva o neutral directamente de la distribución de nucleótidos o bases en los genomas o segmentos genómicos (cromosomas).…”

“…Me pregunté si las bases nucleotídicas (A, T, G y C) estaban distribuidas al azar en un segmento de ADN o cromosoma. El resultado fue que su distribución era tan lejana a la neutralidad o azar que las teorías neutral y casi neutral de la evolución no podían mantenerse [1][2][3][4][5][6]. Para confirmar este resultado inicié el estudio de dinucleótidos cuyas bases estaban separadas por 0, 1, 2, … K sitios nucleotídicos olvidando todo lo que se sabe de estructuras nucleotídicas codificantes o no, organizaciones como centrómeros, telómeros, ADN simple o repetitivo y todo lo que se sabe de la organización del genoma.…”