Using Statistics to Shed Light on the Dynamics of the Human Genome: A Review

Chiaromonte, Francesca; Makova, Kateryna D.

doi:10.1007/978-3-319-11149-0_5

Cited by 2 publications

(2 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…approximately one third of the genome). We assumed that these sequences evolve largely neutrally ( 14 , 88 , 89 , 112 ) and thus, the levels of diversity and divergence reflect variation in mutation frequencies. Within the NCNR subgenome, we were able to analyze 171 653 direct repeats, 2 017 399 inverted repeats, 213 899 mirror repeats, 146 174 A-phased repeats, 108 279 Z-DNA loci and 178 312 G4 loci ( Supplementary Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, we describe distortions in the nucleotide substitution spectrum surrounding G4s. Lastly, we evaluate whether adding non-B DNA loci to statistical models that include known contributing genomic features ( 1 , 12 , 16 , 88 , 89 ) increases the explained share of regional variation in diversity and divergence. Overall, our study measures the contributions of non-B DNA to germline variation in nucleotide substitution frequencies across the human genome.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Non-B DNA: a major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome

Guiblet

Cremona

Harris

et al. 2021

Nucleic Acids Research

Self Cite

View full text Add to dashboard Cite

Approximately 13% of the human genome can fold into non-canonical (non-B) DNA structures (e.g. G-quadruplexes, Z-DNA, etc.), which have been implicated in vital cellular processes. Non-B DNA also hinders replication, increasing errors and facilitating mutagenesis, yet its contribution to genome-wide variation in mutation rates remains unexplored. Here, we conducted a comprehensive analysis of nucleotide substitution frequencies at non-B DNA loci within noncoding, non-repetitive genome regions, their ±2 kb flanking regions, and 1-Megabase windows, using human-orangutan divergence and human single-nucleotide polymorphisms. Functional data analysis at single-base resolution demonstrated that substitution frequencies are usually elevated at non-B DNA, with patterns specific to each non-B DNA type. Mirror, direct and inverted repeats have higher substitution frequencies in spacers than in repeat arms, whereas G-quadruplexes, particularly stable ones, have higher substitution frequencies in loops than in stems. Several non-B DNA types also affect substitution frequencies in their flanking regions. Finally, non-B DNA explains more variation than any other predictor in multiple regression models for diversity or divergence at 1-Megabase scale. Thus, non-B DNA substantially contributes to variation in substitution frequencies at small and large scales. Our results highlight the role of non-B DNA in germline mutagenesis with implications to evolution and genetic diseases.

show abstract