Regional variation in mutation rates

Credit: Marta Tomaszkiewicz

Mutation rates vary at a fine scale - even within individual chromosomes. We are using statistical modeling to study such regional variation in mutation rates. Our analysis of insertions vs. deletions revealed that they are formed, at least in part, by different molecular mechanisms and that, in addition to replication, recombination plays an important role in indel formation (Kvikstad et al. 2007). Employing wavelet transformation techniques, we demonstrated the importance of genomic scale for regional variation in mutation rates (Kvikstad et al. 2009). Using specialized statistical approaches, we have investigated the structure of rate co-variation for four mutation types (point mutations, insertions, deletions, and microsatellite mutations) and simultaneously exploring the associations with multiple genomic features (Ananda et al. 2011). Moreover, we were able to segment the genome into regions with high and low rates of different mutations (Kurupummulage Don, Ananda, et al. 2013). Collaborator: Francesca Chiaromonte.

Press Releases

DNA sequences that can fold into shapes other than the classic double helix tend to have higher mutation rates than other regions in …

Comparisons of DNase Hypersensitive Site (DHS) signals among L1 flanking regions and control.The figure illustrates the distribution of …

Publications

. Non-B DNA: A major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome. NUCLEIC ACIDS RES, 2021.

Regional variation Paper Link

. Human L1 Transposition Dynamics Unraveled with Functional Data Analysis. MOL BIOL EVOL, 2020.

Regional variation Paper Link

. Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate. GENOME RES, 2018.

Regional variation Paper Link Press Release

. IWTomics: testing high-resolution sequence-based `Omics' data at multiple locations and scales. BIOINFORMATICS, 2018.

Microsatellite Regional variation Paper Link

. Genomic Landscape of Human, Bat, and Ex Vivo DNA Transposon Integrations. MOL BIOL EVOL, 2014.

Regional variation Paper Link

. Segmenting the human genome based on states of neutral genetic divergence. P NATL ACAD SCI USA, 2013.

Regional variation Paper Link

. Rescuing Alu: Recovery of New Inserts Shows LINE-1 Preserves Alu Activity through A-Tail Expansion. PLOS GENET, 2012.

Regional variation Paper Link

. Molecular Clocks. eLS, 2008.

Regional variation Paper Link

. Human-macaque comparisons illuminate variation in neutral substitution rates. GENOME BIOL, 2008.

Regional variation Paper Link

. A Macaque's-Eye View of Human Insertions and Deletions: Differences in Mechanisms. PLOS COMPUT BIOL, 2007.

Regional variation Paper Link

. Rapid and asymmetric divergence of duplicate genes in the human gene coexpression network. BMC BIOINFORMATICS, 2006.

Regional variation Paper Link

. Initial sequence of the chimpanzee genome and comparison with the human genome. NATURE, 2005.

Regional variation Paper Link

. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. NATURE, 2004.

Regional variation Sex chromosome Paper Link

. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. NATURE, 2004.

Regional variation Sex chromosome Paper Link

. Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum. NATURE, 2002.

Regional variation Paper Link

. Male-driven evolution. CURR OPIN GENET DEV, 2002.

Regional variation Sex chromosome Paper Link