Non-B DNA and Microsatellite Variation and Evolution

Mitochondrial Mutation Dynamics

Regional Variation in Mutation Rates

Projects

Childhood obesity

Obesity is becoming the major epidemic of the 21st century, and we are studying this disease in an integrated way - from the perspective of genomics, microbiomics, and epigenomics. We are following a large group of newborn children until they are at least 3 years of age.

Mitochondrial mutation dynamics

With sequencing now possible at high depth, we aim to examine mutation process directly, by examining the DNA of children and their parents. Mitochondrial DNA (mtDNA) provides a good starting point for such an investigation due to its compact size and high mutation rate.

Non-B DNA and microsatellite variation and evolution

Approximately 13% of the genome can fold into DNA structures different from the B-form double-helix discovered by Watson and Crick. Such “non-B DNA” structures include cruciforms, triplexes, slipped-strand structures, G-quadruplexes (G4s), Z-DNA, and bent DNA. They form at certain DNA sequence motifs that are ubiquitous in the genomes of prokaryotes and eukaryotes.

Regional variation in mutation rates

Mutation rates vary at a fine scale - even within individual chromosomes. We are using statistical modeling to study such regional variation in mutation rates. Moreover, we are able to segment the genome into regions with high and low rates of different mutation types.

Sex chromosome evolution

We are determining the gene repertoire and structure of the Y chromosome in several mammalian species. The Y chromosome has very high rates of mutation compared with other chromosomes in the mammalian genome due to a higher number of cell divisions in the male than female germ line.

News

More News

Congratulations to Xinru Zhang who has been named as one of the recipients of the Jeanette Ritter Mohnkern Graduate Student Scholarship in Biology for the 2022/2023 fiscal year!

Apr 14, 2023

Congratulations to Xinru Zhang on publishing a manuscript in Nature Communications

Feb 20, 2023

Congratulations to Edmundo Torres-González for winning the GlaxoSmithKline (GSK) Graduate Fellowship from the Eberly College of Science in partnership with the College of Medicine and the Huck Institutes of the Life Sciences for the 2023-2024 academic year.

Feb 2, 2023

Congratulations to Sarah Craig on winning the Center for Human Evolution and Diversity grant

Jan 23, 2023

Congratulations to Barbara Arbeithuber, a former postdoc from the lab, on winning the 2021 EMGS New Investigator Presentation Award!

Oct 13, 2021

Press Releases

More Press Releases

Complete X and Y chromosome sequences of living great ape species determined

Newly generated, complete “end-to-end” reference genomes for the sex chromosomes of five great ape species and one lesser ape species — …

Penn State Eberly College of Science

May 29, 2024

DNA sequence of the human Y chromosome fully determined for first time

Listen to the Science Friday podcast where Adam Phillippy and Kateryna Makova discuss the challenges of sequencing the Y chromosome, …

Francisco Tutella

Aug 23, 2023

Are egg cells in aging primates protected from mutations?

New mutations occur at increasing rates in the mitochondrial genomes of developing egg cells in aging rhesus monkeys, but the increases …

Sam Sholtis

Apr 4, 2022

Recent Publications

More Publications

SK Mohanty, F Chiaromonte, KD Makova. Evolutionary Dynamics of G-Quadruplexes in Human and Other Great Ape Telomere-to-Telomere Genomes. BIORXIV, 2024.

Paper Link

L Smeds, K Kamali, KD Makova. Non-canonical DNA in human and other ape telomere-to-telomere genomes. BIORXIV, 2024.

Paper Link

D Yoo, A Rhie, P Hebbar, F Antonacci, GA Logsdon, SJ Solar, D Antipov, BD Pickett, Y Safonova, F Montinaro, Y Luo, J Malukiewicz, JM Storer, J Lin, AN Sequeira, RJ Mangan, G Hickey, GM Anez, P Balachandran, A Bankevich, CR Beck, A Biddanda, M Borchers, GG Bouffard, E Brannan, SY Brooks, L Carbone, L Carrel, AP Chan, J Crawford, M Diekhans, E Engelbrecht, C Feschotte, G Formenti, GH Garcia, L de Gennaro, D Gilbert, RE Green, A Guarracino, I Gupta, D Haddad, J Han, RS Harris, GA Hartley, WT Harvey, M Hiller, K Hoekzema, ML Houck, H Jeong, K Kamali, M Kellis, B Kille, C Lee, Y Lee, W Lees, AP Lewis, Q Li, M Loftus, YHE Loh, H Loucks, J Ma, Y Mao, JFI Martinez, P Masterson, RC McCoy, B McGrath, S McKinney, BS Meyer, KH Miga, SK Mohanty, KM Munson, K Pal, M Pennell, PA Pevzner, D Porubsky, T Potapova, FR Ringeling, JL Rocha, OA Ryder, S Sacco, S Saha, T Sasaki, MC Schatz, NJ Schork, C Shanks, L Smeds, DR Son, C Steiner, AP Sweeten, MG Tassia, F Thibaud-Nissen, E Torres-González, M Trivedi, W Wei, J Wertz, M Yang, P Zhang, S Zhang, Y Zhang, Z Zhang, SA Zhao, Y Zhu, ED Jarvis, JL Gerton, I Rivas-González, B Paten, ZA Szpiech, CD Huber, TL Lenz, MK Konkel, SV Yi, S Canzar, CT Watson, PH Sudmant, E Molloy, E Garrison, CB Lowe, M Ventura, RJ O’Neill, S Koren, KD Makova, AM Phillippy, EE Eichler. Complete sequencing of ape genomes. BIORXIV, 2024.

Paper Link

M Cechova, KD Makova. The ape Y chromosome evolves extremely rapidly, but the X chromosome is conserved. NATURE, 2024.

PDF Sex chromosome Video Paper Link

KD Makova, BD Pickett, RS Harris, GA Hartley, M Cechova, K Pal, S Nurk, D Yoo, Q Li, P Hebbar, BC McGrath, F Antonacci, M Aubel, A Biddanda, M Borchers, E Bomberg, GG Bouffard, SY Brooks, L Carbone, L Carrel, A Carroll, PC Chang, CS Chin, DE Cook, SJC Craig, L de Gennaro, M Diekhans, A Dutra, GH Garcia, PGS Grady, RE Green, D Haddad, P Hallast, WT Harvey, G Hickey, DA Hillis, SJ Hoyt, H Jeong, K Kamali, SL Kosakovsky Pond, TM LaPolice, C Lee, AP Lewis, YE Loh, P Masterson, RC McCoy, P Medvedev, KH Miga, KM Munson, E Pak, B Paten, BJ Pinto, T Potapova, A Rhie, JL Rocha, F Ryabov, OA Ryder, S Sacco, K Shafin, VA Shepelev, V Slon, SJ Solar, JM Storer, PH Sudmant, Sweetalana, A Sweeten, MG Tassia, F Thibaud-Nissen, M Ventura, MA Wilson, AC Young, H Zeng, X Zhang, ZA Szpiech, CD Huber, JL Gerton, SV Yi, MC Schatz, IA Alexandrov, S Koren, RJ O’Neill, E Eichler, AM Phillippy. The Complete Sequence and Comparative Analysis of Ape Sex Chromosomes. NATURE, 2024.

Sex chromosome Video Paper Link Press release

D Lariviere, SJC Craig, IM Paul, E Hohman, JS Savage, RO Wright, F Chiaromonte, KD Makova, ML Reimherr. Methylation profiles at birth linked to early childhood obesity. J DEV ORIG HEALTH DIS, 2024.

Childhood Obesity Paper Link

A Greshnova, K Pal, JFI Martinez, S Canzar, KD Makova. Transcript Isoform Diversity of Y Chromosome Ampliconic Genes of Great Apes Uncovered Using Long Reads and Telomere-to-Telomere Reference Genome Assemblies. BIORXIV, 2024.

Sex chromosome Paper Link

A Lahnsteiner, SJC Craig, K Kamali, B Weissensteiner, B McGrath, A Risch, KD Makova. In vivo detection of DNA secondary structures using Permanganate/S1 Footprinting with Direct Adapter Ligation and Sequencing (PDAL-Seq). METHODS IN ENZYMOLOGY, 2024.

Non-B DNA & Microsatellite Paper Link

M Tomaszkiewicz, K Sahlin, P Medvedev, KD Makova. Transcript Isoform Diversity of Ampliconic Genes on the Y Chromosome of Great Apes. GENOME BIOL EVOL, 2023.

Sex chromosome Paper Link

A Rhie, S Nurk, M Cechova, SJ Hoyt, DJ Taylor, N Altemose, PW Hook, S Koren, M Rautiainen, IA Alexandrov, J Allen, M Asri, AV Bzikadze, N-C Chen, C-S Chin, M Diekhans, P Flicek, G Formenti, A Fungtammasan, CG Giron, E Garrison, A Gershman, JL Gerton, PGS Grady, A Guarracino, L Haggerty, R Halabian, NF Hansen, R Harris, GA Hartley, WT Harvey, M Haukness, J Heinz, T Hourlier, RM Hubley, SE Hunt, S Hwang, M Jain, RK Kesharwani, AP Lewis, H Li, GA Logsdon, JK Lucas, W Makalowski, C Markovic, FJ Martin, AM McCartney, RC McCoy, J McDaniel, BM McNulty, P Medvedev, A Mikheenko, KM Munson, TD Murphy, HE Olsen, ND Olson, LF Paulin, D Porubsky, T Potapova, F Ryabov, SL Salzberg, MEG Sauria, FJ Sedlazeck, K Shafin, VA Shepelev, A Shumate, JM Storer, L Surapaneni, AM Taravella Oill, F Thibaud-Nissen, W Timp, M Tomaszkiewicz, MR Vollger, BP Walenz, AC Watwood, MH Weissensteiner, AM Wenger, MA Wilson, S Zarate, Y Zhu, JM Zook, EE Eichler, RJ O’Neill, MC Schatz, KH Miga, KD Makova, AM Phillippy. The complete sequence of a human Y chromosome. NATURE, 2023.

Sex chromosome Paper Link