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.
Regional variation in mutation rates
Collaborators
Visiting Research Professor
Press Releases
A new class of functional elements in the human genome?
Some regions of the human genome where the DNA can fold into unusual three-dimensional structures called G-quadruplexes (G4s) show …
Unusual DNA folding increases the rates of mutations
DNA sequences that can fold into shapes other than the classic double helix tend to have higher mutation rates than other regions in …
Scientists take a step toward understanding 'jumping genes' effect on the genome
Comparisons of DNase Hypersensitive Site (DHS) signals among L1 flanking regions and control.The figure illustrates the distribution of …
Publications
X Zhang, B Fang, YF Huang.
Transcription factor binding sites are frequently under accelerated evolution in primates.
NAT COMMUN,
2023.
WM Guiblet, MA Cremona, RS Harris, D Chen, KA Eckert, F Chiaromonte, Y Huang, KD Makova.
Non-B DNA: A major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome.
NUCLEIC ACIDS RES,
2021.
D Chen, MA Cremona, Z Qi, RD Mitra, F Chiaromonte, KD Makova.
Human L1 Transposition Dynamics Unraveled with Functional Data Analysis.
MOL BIOL EVOL,
2020.
WM Guiblet, MA Cremona, M Cechova, RS Harris, I Kejnovská, E Kejnovsky, KA Eckert, F Chiaromonte, KD Makova.
Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate.
GENOME RES,
2018.
Regional variation Non-B DNA & Microsatellite Paper Link Press Release
MA Cremona, A Pini, F Cumbo, KD Makova, F Chiaromonte, S Vantini.
IWTomics: testing high-resolution sequence-based `Omics' data at multiple locations and scales.
BIOINFORMATICS,
2018.
R Campos-Sánchez, MA Cremona, A Pini, F Chiaromonte, KD Makova.
Integration and Fixation Preferences of Human and Mouse Endogenous Retroviruses Uncovered with Functional Data Analysis.
PLOS COMPUT BIOL,
2016.
KD Makova, RC Hardison.
The effects of chromatin organization on variation in mutation rates in the genome.
NAT REV GENET,
2015.
F Chiaromonte, KD Makova.
Using Statistics to Shed Light on the Dynamics of the Human Genome: A Review.
CONTRIB STAT,
2015.
R Campos-Sánchez, A Kapusta, C Feschotte, F Chiaromonte, KD Makova.
Genomic Landscape of Human, Bat, and Ex Vivo DNA Transposon Integrations.
MOL BIOL EVOL,
2014.
P Kuruppumullage Don, G Ananda, F Chiaromonte, KD Makova.
Segmenting the human genome based on states of neutral genetic divergence.
P NATL ACAD SCI USA,
2013.
BJ Wagstaff, DJ Hedges, RS Derbes, R Campos-Sánchez, F Chiaromonte, KD Makova, AM Roy-Engel.
Rescuing Alu: Recovery of New Inserts Shows LINE-1 Preserves Alu Activity through A-Tail Expansion.
PLOS GENET,
2012.
A Fungtammasan, E Walsh, F Chiaromonte, KA Eckert, KD Makova.
A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?.
GENOME RES,
2012.
MA Wilson Sayres, C Venditti, M Pagel, KD Makova.
DO VARIATIONS IN SUBSTITUTION RATES AND MALE MUTATION BIAS CORRELATE WITH LIFE-HISTORY TRAITS? A STUDY OF 32 MAMMALIAN GENOMES.
EVOLUTION,
2011.
G Ananda, F Chiaromonte, KD Makova.
A genome-wide view of mutation rate co-variation using multivariate analyses.
GENOME BIOL,
2011.
EM Kvikstad, KD Makova.
The (r)evolution of SINE versus LINE distributions in primate genomes: Sex chromosomes are important.
GENOME RES,
2010.
C Park, KD Makova.
Coding region structural heterogeneity and turnover of transcription start sites contribute to divergence in expression between duplicate genes.
GENOME BIOL,
2009.
EM Kvikstad, F Chiaromonte, KD Makova.
Ride the wavelet: A multiscale analysis of genomic contexts flanking small insertions and deletions.
GENOME RES,
2009.
S Tyekucheva, KD Makova, JE Karro, RC Hardison, W Miller, F Chiaromonte.
Human-macaque comparisons illuminate variation in neutral substitution rates.
GENOME BIOL,
2008.
EM Kvikstad, S Tyekucheva, F Chiaromonte, KD Makova.
A Macaque's-Eye View of Human Insertions and Deletions: Differences in Mechanisms.
PLOS COMPUT BIOL,
2007.
MP Goetting-Minesky, KD Makova.
Mammalian Male Mutation Bias: Impacts of Generation Time and Regional Variation in Substitution Rates.
J MOL EVOL,
2006.
J Taylor, S Tyekucheva, M Zody, F Chiaromonte, KD Makova.
Strong and Weak Male Mutation Bias at Different Sites in the Primate Genomes: Insights from the Human-Chimpanzee Comparison.
MOL BIOL EVOL,
2006.
W-Y Chung, R Albert, I Albert, A Nekrutenko, KD Makova.
Rapid and asymmetric divergence of duplicate genes in the human gene coexpression network.
BMC BIOINFORMATICS,
2006.
KD Makova, H Norton.
Worldwide polymorphism at the MC1R locus and normal pigmentation variation in humans.
PEPTIDES,
2005.
The Chimpanzee Sequencing and Analysis Consortium, RH Waterson, ES Lander, RK Wilson.
Initial sequence of the chimpanzee genome and comparison with the human genome.
NATURE,
2005.
A Nekrutenko, S Wadhawan, MP Goetting-Minesky, KD Makova.
Oscillating Evolution of a Mammalian Locus with Overlapping Reading Frames: An XLαs/ALEX Relay.
PLOS GENET,
2005.
International Chicken Genome Sequencing Consortium, LW Hillier, W Miller, E Birney, W Warren, RC Hardison, CP Ponting, P Bork, DW Burt, MAM Groenen, ME Delany, JB Dodgson, AT Chinwalla, PF Cliften, SW Clifton, KD Delehaunty, C Fronick, RS Fulton, TA Graves, C Kremitzki, D Layman, V Magrini, JD McPherson, TL Miner, P Minx, WE Nash, MN Nhan, JO Nelson, LG Oddy, CS Pohl, J Randall-Maher, SM Smith, JW Wallis, S-P Yang, MN Romanov, CM Rondelli, B Paton, J Smith, D Morrice, L Daniels, HG Tempest, L Robertson, JS Masabanda, DK Griffin, A Vignal, V Fillon, L Jacobbson, S Kerje, L Andersson, RPM Crooijmans, J Aerts, JJ van der Poel, H Ellegren, RB Caldwell, SJ Hubbard, DV Grafham, AM Kierzek, SR McLaren, IM Overton, H Arakawa, KJ Beattie, Y Bezzubov, PE Boardman, JK Bonfield, MDR Croning, RM Davies, MD Francis, SJ Humphray, CE Scott, RG Taylor, C Tickle, WRA Brown, J Rogers, J-M Buerstedde, SA Wilson, L Stubbs, I Ovcharenko, L Gordon, S Lucas, MM Miller, H Inoko, T Shiina, J Kaufman, J Salomonsen, K Skjoedt, GK-S Wong, J Wang, B Liu, J Wang, J Yu, H Yang, M Nefedov, M Koriabine, PJ deJong, L Goodstadt, C Webber, NJ Dickens, I Letunic, M Suyama, D Torrents, C von Mering, EM Zdobnov, KD Makova, A Nekrutenko, L Elnitski, P Eswara, DC King, S Yang, S Tyekucheva, A Radakrishnan, RS Harris, F Chiaromonte, J Taylor, J He, M Rijnkels, S Griffiths-Jones, A Ureta-Vidal, MM Hoffman, J Severin, SMJ Searle, AS Law, D Speed, D Waddington, Z Cheng, E Tuzun, EE Eichler, Z Bao, P Flicek, DD Shteynberg, MR Brent, JM Bye, EJ Huckle, S Chatterji, C Dewey, L Pachter, A Kouranov, Z Mourelatos, AG Hatzigeorgiou, AH Paterson, R Ivarie, M Brandstrom, E Axelsson, N Backstrom, S Berlin, MT Webster, O Pourquie, A Reymond, C Ucla, SE Antonarakis, M Long, JJ Emerson, E Betrán, I Dupanloup, H Kaessmann, AS Hinrichs, G Bejerano, TS Furey, RA Harte, B Raney, A Siepel, WJ Kent, D Haussler, E Eyras, R Castelo, JF Abril, S Castellano, F Camara, G Parra, R Guigo, G Bourque, G Tesler, PA Pevzner, AFA Smit, LA Fulton, ER Mardis, RK Wilson.
Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution.
NATURE,
2004.
Rat Genome Sequencing Project Consortium, RA Gibbs, GM Weinstock, ML Metzker, DM Muzny, EJ Sodergren, S Scherer, G Scott, D Steffen, KC Worley, PE Burch, GO Okwuonu, S Hines, LR Lewis, C DeRamo, O Delgado, S Dugan-Rocha, G Miner, M Morgan, AC Hawes, R Gill, CRA Holt, MD Adams, PG Amanatides, H Baden-Tillson, M Barnstead, S Chin, CA Evans, S Ferriera, C Fosler, A Glodek, Z Gu, D Jennings, CL Kraft, T Nguyen, CM Pfannkoch, C Sitter, GG Sutton, JC Venter, T Woodage, D Smith, H-M Lee, E Gustafson, P Cahill, A Kana, L Doucette-Stamm, K Weinstock, K Fechtel, RB Weiss, DM Dunn, ED Green, RW Blakesley, GG Bouffard, PJ de Jong, K Osoegawa, B Zhu, MA Marra, JE Schein, I Bosdet, C Fjell, SM Jones, M Krzywinski, C Mathewson, A Siddiqui, N Wye, JD McPherson, S Zhao, CM Fraser, J Shetty, S Shatsman, K Geer, Y Chen, S Abramzon, WC Nierman, RA Gibbs, GM Weinstock, PH Havlak, R Chen, K James Durbin, A Egan, Y Ren, HX-Z Song, B Li, Y Liu, X Qin, S Cawley, GM Weinstock, KC Worley, AJ Cooney, RA Gibbs, LM D’Souza, K Martin, J Qian Wu, ML Gonzalez-Garay, AR Jackson, KJ Kalafus, MP McLeod, A Milosavljevic, D Virk, A Volkov, DA Wheeler, Z Zhang, JA Bailey, EE Eichler, E Tuzun, E Birney, E Mongin, A Ureta-Vidal, C Woodwark, EM Zdobnov, P Bork, M Suyama, D Torrents, M Alexandersson, BJ Trask, JM Young, D Smith, H Huang, K Fechtel, H Wang, H Xing, K Weinstock, S Daniels, D Gietzen, J Schmidt, K Stevens, U Vitt, J Wingrove, F Camara, M Mar Albà, JF Abril, R Guigo, AFA Smit, I Dubchak, EM Rubin, O Couronne, A Poliakov, N Hübner, D Ganten, C Goesele, O Hummel, T Kreitler, Y-A Lee, J Monti, H Schulz, H Zimdahl, H Himmelbauer, H Lehrach, HJ Jacob, S Bromberg, J Gullings-Handley, MI Jensen-Seaman, AE Kwitek, J Lazar, D Pasko, PJ Tonellato, S Twigger, CP Ponting, JM Duarte, S Rice, L Goodstadt, SA Beatson, RD Emes, EE Winter, C Webber, P Brandt, G Nyakatura, M Adetobi, F Chiaromonte, L Elnitski, P Eswara, RC Hardison, M Hou, D Kolbe, KD Makova, W Miller, A Nekrutenko, C Riemer, S Schwartz, J Taylor, S Yang, Y Zhang, K Lindpaintner, TD Andrews, M Caccamo, M Clamp, L Clarke, V Curwen, R Durbin, E Eyras, SMJ Searle, GM Cooper, S Batzoglou, M Brudno, A Sidow, EA Stone, J Craig Venter, BA Payseur, G Bourque, C López-Otín, XS Puente, K Chakrabarti, S Chatterji, C Dewey, L Pachter, N Bray, VB Yap, A Caspi, G Tesler, PA Pevzner, D Haussler, KM Roskin, R Baertsch, H Clawson, TS Furey, AS Hinrichs, D Karolchik, WJ Kent, KR Rosenbloom, H Trumbower, M Weirauch, DN Cooper, PD Stenson, B Ma, MR Brent, M Arumugam, DD Shteynberg, RR Copley, MS Taylor, H Riethman, U Mudunuri, J Peterson, M Guyer, A Felsenfeld, S Old, S Mockrin, F Collins.
Genome sequence of the Brown Norway rat yields insights into mammalian evolution.
NATURE,
2004.
KD Makova, S Yang, F Chiaromonte.
Insertions and Deletions Are Male Biased Too: A Whole-Genome Analysis in Rodents.
GENOME RES,
2004.
PR John, KD Makova, W-H Li, T Jenkins, M Ramsay.
DNA Polymorphism and Selection at the Melanocortin-1 Receptor Gene in Normally Pigmented Southern African Individuals.
ANN NY ACAD SCI,
2003.
KD Makova, W-H Li.
Divergence in the Spatial Pattern of Gene Expression Between Human Duplicate Genes.
GENOME RES,
2003.
J Mu, J Duan, KD Makova, DA Joy, CQ Huynh, OH Branch, W-H Li, X-Z Su.
Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum.
NATURE,
2002.
KD Makova, W-H Li.
Strong male-driven evolution of DNA sequences in humans and apes.
NATURE,
2002.
W-H Li, S Yi, KD Makova.
Male-driven evolution.
CURR OPIN GENET DEV,
2002.
A Nekrutenko, KD Makova, W-H Li.
The K A/K S Ratio Test for Assessing the Protein-Coding Potential of Genomic Regions: An Empirical and Simulation Study.
GENOME RES,
2002.
KD Makova, M Ramsay, T Jenkins, W-H Li.
Human DNA Sequence Variation in a 6.6-kb Region Containing the Melanocortin 1 Receptor Promoter.
GENETICS,
2001.
J-C Liu, KD Makova, RM Adkins, S Gibson, W-H Li.
Episodic Evolution of Growth Hormone in Primates and Emergence of the Species Specificity of Human Growth Hormone Receptor.
MOL BIOL EVOL,
2001.