Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 54329 Моделирование в биофизике Modelling in biophycis Моделирование в биофизике ON THE PECULIARITIES OF THE MECHANISM OF POINT SPONTANEOUS MUTATIONS IN HUMAN Y-CHROMOSOME STRUCTURE ОБ ОСОБЕННОСТЯХ МЕХАНИЗМА ТОЧЕЧНЫХ СПОНТАННЫХ МУТАЦИЙ В СТРУКТУРЕ Y-ХРОМОСОМЫ ЧЕЛОВЕКА Самченко А А Samchenko A A Киселев С С Kiselev S S Кондратьев М С Kondratyev M S Комаров В. М. Komarov V. M. komarov_vm@mail.ru

доктор физико-математических наук;

doctor of physical and mathematical sciences;

 Институт биофизики клетки РАН ru Institute of Cell Biophysics of RAS ru Институт биофизики клетки РАН ru Institute of Cell Biophysics of RAS ru Институт биофизики клетки РАН ru Institute of Cell Biophysics of RAS ru Институт биофизики клетки РАН Пущино Россия Institute of Cell Biophysics of RAS Pushchino Russian Federation 25 09 2018 25 09 2018 3 3 568 573 20 09 2018 20 09 2018 https://rusjbpc.ru/en/nauka/article/54329/view

В работе с использованием методов сравнительной геномики проанализирована специфика распределения мононуклеотидных и смешанных треков W- и S-типа в структуре ДНК половой Y-хромосомы и в близкой к ней по размерам 22 хромосомы человека. Обнаружено, что у Y-хромосомы в ее регуляторной области наблюдается аномально высокая плотность S (G/C)-треков, состоящих из относительно коротких (до 6 пар нуклеотидов) последовательностей из G/C- (и C/G-) пар. Для 22 хромосомы небольшая избыточность таких S-треков наблюдается лишь в структуре ее кодирующих областей (экзонов). Ранее в своих исследованиях мы указывали на не тривиальную, повышенную способность G/C-пар по сравнению с А/Т-парами к спонтанному изменению геометрии своего комплементарного Н-связывания (из-за разных размерностей скрытого структурного полиморфизма уотсон-криковских G/C- и А/Т-пар). В данном случае, выявленная большая плотность S(G/C)-треков в межгенной части Y-хромосомы указывает на возможное увеличение числа событий спонтанного нарушения комплементарности в этой области по сравнению с аналогичными событиями в аутосомной 22 хромосоме. То есть, таким способом может инициироваться аномально высокая частота точечных спонтанных мутаций Y-хромосомы по сравнению с частотой аналогичных мутаций в других хромосомах человека. Что и наблюдается экспериментально.

The specific character of distribution of mononucleotide tracts and mixed W or S tracts in human Y and 22 chromosomes was analysed by comparative genomic approaches. It was found that in regulatory regions of Y chromosome anomalously high density of S (G/C)-tracts consisting of relatively short sequences (up to 6 base pairs) was observed. In primary structure of coding regions (exons) of 22 chromosome only a small redundancy of S- tracts was discovered. Previously in our papers we pointed to the non-trivial, increased ability of G/C pairs to a spontaneous change in the geometry of its complementary H-binding (because of the different dimensions of the hidden structural polymorphism of Watson-Crick G/C and A/T base pairs) in comparison with A/T pairs. In this case, revealed high density of S(G/C)-tracts in intergenic regions of Y chromosome indicated to possibility of increasing in the number of events of spontaneous complementarity lesions in this areas in comparison with similar events in the autosomic 22 chromosome. That is, in this way an abnormally high frequency of spontaneous point mutations in the Y chromosome compared with the frequency of similar mutations in other human chromosomes can be initiated. This is observed experimentally.

 ДНК структура хромосом доминирование S-треков структурный полиморфизм уотсон-криковских пар частота спонтанных мутаций DNA chromosome structure redundancy of S-tracts structural polymorphism of Watson-Crick base pairs frequency of spontaneous mutations

Ali S., Hasnain S.E. Genomics of the human Y-chromosome-1. Association with male infertility. Gene, 2003, vol. 4 (321), pp. 25-37. Ali S., Hasnain S.E. Genomics of the human Y-chromosome-1. Association with male infertility. Gene, 2003, vol. 4 (321), pp. 25-37. Lindblad-Toh K. [et al.] Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature, 2005, vol. 438, pp. 803-819. Lindblad-Toh K. [et al.] Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature, 2005, vol. 438, pp. 803-819. Graves J.A.M. Sex Chromosome Specialization and Degeneration in Mammals. Cell, 2006, vol. 124 (5), pp. 901-914. Graves J.A.M. Sex Chromosome Specialization and Degeneration in Mammals. Cell, 2006, vol. 124 (5), pp. 901-914. Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature, 2002, vol. 420, pp. 520-562. Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature, 2002, vol. 420, pp. 520-562. Wen-Hsiung Li [et al.] Male-driven evolution. Current Opinion in Genetics & Development, 2002, vol. 12, pp. 650-656. Wen-Hsiung Li [et al.] Male-driven evolution. Current Opinion in Genetics & Development, 2002, vol. 12, pp. 650-656. Ballantyne K.N. [et al.] Mutability of Y-Chromosomal Microsatellites: Rates, Characteristics, Molecular Bases, and Forensic Implications. The American Journal of Human Genetics, 2010, vol. 87, pp. 341-353. Ballantyne K.N. [et al.] Mutability of Y-Chromosomal Microsatellites: Rates, Characteristics, Molecular Bases, and Forensic Implications. The American Journal of Human Genetics, 2010, vol. 87, pp. 341-353. Lynch M., Sung W., Morris K., Coffey N., Landry C.R., Dopman E.B., Dickinson W.J., Okamoto K., Kulkarni S., Hartl D.L., Thomas W.K. A genome-wide view of the spectrum of spontaneous mutations in yeast. Proc. Natl. Acad. Sci. USA, 2008, vol. 105 (27), pp. 9272-9277. Lynch M., Sung W., Morris K., Coffey N., Landry C.R., Dopman E.B., Dickinson W.J., Okamoto K., Kulkarni S., Hartl D.L., Thomas W.K. A genome-wide view of the spectrum of spontaneous mutations in yeast. Proc. Natl. Acad. Sci. USA, 2008, vol. 105 (27), pp. 9272-9277. Dillon M.M., Sung W., Lynch M., Cooper V.S. The Rate and Molecular Spectrum of Spontaneous Mutations in the GC-Rich Multichromosome Genome of Burkholderia cenocepacia. Genetics, 2015, vol. 200, pp. 935-946. Dillon M.M., Sung W., Lynch M., Cooper V.S. The Rate and Molecular Spectrum of Spontaneous Mutations in the GC-Rich Multichromosome Genome of Burkholderia cenocepacia. Genetics, 2015, vol. 200, pp. 935-946. Mehrotra S., Goyal V. Repetitive Sequences in Plant Nuclear DNA: Types, Distribution, Evolution and Function. Genomics Proteomics Bioinformatics, 2014, vol. 12 (4), pp. 164-171. Mehrotra S., Goyal V. Repetitive Sequences in Plant Nuclear DNA: Types, Distribution, Evolution and Function. Genomics Proteomics Bioinformatics, 2014, vol. 12 (4), pp. 164-171. Forster H., Röhl A., Lünnemann P., Brinkmann C., Zerjal T., Tyler-Smith C., Brinkmann B. A Short Tandem Repeat-Based Phylogeny for the Human Y Chromosome. The American Journal of Human Genetics, 2000, vol. 67 (1), pp. 182-196. Forster H., Röhl A., Lünnemann P., Brinkmann C., Zerjal T., Tyler-Smith C., Brinkmann B. A Short Tandem Repeat-Based Phylogeny for the Human Y Chromosome. The American Journal of Human Genetics, 2000, vol. 67 (1), pp. 182-196. Jobling M.A., Tyler-Smith C. Y-chromosomal SNP haplotype diversity in forensic analysis. Forensic Science International, 2001, vol. 118, pp. 158-162. Jobling M.A., Tyler-Smith C. Y-chromosomal SNP haplotype diversity in forensic analysis. Forensic Science International, 2001, vol. 118, pp. 158-162. Jobling M.A., Tyler-Smith C. The human Y chromosome: an evolutionary marker comes of age”. Nature Reviews. Genetics, 2003, vol. 4, pp.598-612. Jobling M.A., Tyler-Smith C. The human Y chromosome: an evolutionary marker comes of age”. Nature Reviews. Genetics, 2003, vol. 4, pp.598-612. Subirana J.A., Messeguer X. The distribution of alternating AT sequences in eukaryotic genomes suggests a role in homologous chromosome recognition in meiosis. J. Theor. Biol., 2011, vol. 283, pp. 28-34. Subirana J.A., Messeguer X. The distribution of alternating AT sequences in eukaryotic genomes suggests a role in homologous chromosome recognition in meiosis. J. Theor. Biol., 2011, vol. 283, pp. 28-34. Marx K.A., Zhou Y., Kishawi I.Q. Evidence for Long Poly(dA).Poly(dT) Tracts in D.Discoideum DNA at High Frequencies and Their Preferential Avoidance of Nucleosomal DNA Core Regions. J. Biomol. Struct. & Dyn., 2006, vol. 23, pp. 429-446. Marx K.A., Zhou Y., Kishawi I.Q. Evidence for Long Poly(dA).Poly(dT) Tracts in D.Discoideum DNA at High Frequencies and Their Preferential Avoidance of Nucleosomal DNA Core Regions. J. Biomol. Struct. & Dyn., 2006, vol. 23, pp. 429-446. Subirana J.A., Messeguer X. The most frequent short sequences in non-coding DNA. Nucleic Acids Res., 2010, vol. 38 (4), pp. 1172-1180. Subirana J.A., Messeguer X. The most frequent short sequences in non-coding DNA. Nucleic Acids Res., 2010, vol. 38 (4), pp. 1172-1180. Yagil G. The frequency of two-base tracts in eukaryotic genomes. J. Mol. Evol., 1993, vol. 37, pp. 123-130. Yagil G. The frequency of two-base tracts in eukaryotic genomes. J. Mol. Evol., 1993, vol. 37, pp. 123-130. Yagil G. DNA tracts composed of only two bases concentrate in gene promoters. Genomics, 2006, vol. 87, pp. 591-597. Yagil G. DNA tracts composed of only two bases concentrate in gene promoters. Genomics, 2006, vol. 87, pp. 591-597. Shomer D., Yagil G. Long W tracts are over-represented in the E.coli and H.influenzae genomes. Nucl.AcidsRes., 1999, vol. 27, pp. 4491-4480. Shomer D., Yagil G. Long W tracts are over-represented in the E.coli and H.influenzae genomes. Nucl.AcidsRes., 1999, vol. 27, pp. 4491-4480. Киселев C.C., Комаров В.М., Масулис И.С., Озолинь О.Н. Распределение мононуклеотидных повторов в бактериальных хромосомах. A/T-треки преобладают над G/C-треками. Компьют. исследов. моделир., 2010, т. 2, c. 183-187. [Kiselev S.S., Komarov V.M., Masulis I.S., Ozoline O.N. Distribution of mononucleotide repeats in bacterial chromosomes. Redundancy of A/T-tracts under G/C-tracts. Computer researches & modelling, 2010, vol. 2, pp. 183-187. (In Russ.)] Kiselev C.C., Komarov V.M., Masulis I.S., Ozolin' O.N. Raspredelenie mononukleotidnyh povtorov v bakterial'nyh hromosomah. A/T-treki preobladayut nad G/C-trekami. Komp'yut. issledov. modelir., 2010, t. 2, c. 183-187. [Kiselev S.S., Komarov V.M., Masulis I.S., Ozoline O.N. Distribution of mononucleotide repeats in bacterial chromosomes. Redundancy of A/T-tracts under G/C-tracts. Computer researches & modelling, 2010, vol. 2, pp. 183-187. (In Russ.)] Piazza F., Lio P. Statistical analysis of simple repeats in the human genome. Physica A, 2005, vol. 347, pp. 472-488. Piazza F., Lio P. Statistical analysis of simple repeats in the human genome. Physica A, 2005, vol. 347, pp. 472-488. Dechering K.J., Cuelenaere K., Konings R.N.H., Leunissen J.A.M. Distinct frequency-distributions of homopolymeric DNA tracts in different genomes. Nucleic Acids Research, 1998, vol. 26, pp. 4056-4062. Dechering K.J., Cuelenaere K., Konings R.N.H., Leunissen J.A.M. Distinct frequency-distributions of homopolymeric DNA tracts in different genomes. Nucleic Acids Research, 1998, vol. 26, pp. 4056-4062. Самченко А.А., Киселев С.С., Кабанов А.В., Кондратьев М.С., Комаров В.М. О природе доминирования олигомерных (dA:dT)n треков в структуре геномов эукариот. Биофизика, 2016, т. 6, с. 1045-1058. [Samchenko A.A., Kiselev S.S., Kabanov A.V., Kondratjev M.S., Komarov V.M. On the nature of oligo (dA:dT)n tracks domination in the structure of eukaryotic genomes. Biofizika, 2016, vol. 6, pp. 1045-1058. (In Russ.)] Samchenko A.A., Kiselev S.S., Kabanov A.V., Kondrat'ev M.S., Komarov V.M. O prirode dominirovaniya oligomernyh (dA:dT)n trekov v strukture genomov eukariot. Biofizika, 2016, t. 6, s. 1045-1058. [Samchenko A.A., Kiselev S.S., Kabanov A.V., Kondratjev M.S., Komarov V.M. On the nature of oligo (dA:dT)n tracks domination in the structure of eukaryotic genomes. Biofizika, 2016, vol. 6, pp. 1045-1058. (In Russ.)] Mackewicz D. [et al.] Distribution of Recombination Hotspots in the Human Genome - A Comparison of Computer Simulations with Real Data. PLOS ONE, 2013, vol. 8, e65272. Mackewicz D. [et al.] Distribution of Recombination Hotspots in the Human Genome - A Comparison of Computer Simulations with Real Data. PLOS ONE, 2013, vol. 8, e65272. Cooper D.N., Youssoufian H. The CpG dinucleotide and human genetic disease. Hum Genet., 1988, vol. 78, pp. 151-155. Cooper D.N., Youssoufian H. The CpG dinucleotide and human genetic disease. Hum Genet., 1988, vol. 78, pp. 151-155. Sved J., Bird A. The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model. Proc. Natl. Acad. Sci USA, 1990, vol. 87, pp. 4692-4696. Sved J., Bird A. The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model. Proc. Natl. Acad. Sci USA, 1990, vol. 87, pp. 4692-4696. Fryxell K.J., Moon W.J. CpG mutation rates in the human genome are highly dependent on local GC content. Mol. Biol. Evol., 2005, vol. 22, pp. 650-658. Fryxell K.J., Moon W.J. CpG mutation rates in the human genome are highly dependent on local GC content. Mol. Biol. Evol., 2005, vol. 22, pp. 650-658.