PhaseDancer: a novel targeted assembler of segmental duplications unravels the complexity of the human chromosome 2 fusion going from 48 to 46 chromosomes in hominin evolution

Barbara Poszewiecka; Krzysztof Gogolewski; Justyna A Karolak; Paweł Stankiewicz; Anna Gambin

doi:10.1186/s13059-023-03022-8

PhaseDancer: a novel targeted assembler of segmental duplications unravels the complexity of the human chromosome 2 fusion going from 48 to 46 chromosomes in hominin evolution

Genome Biol. 2023 Sep 11;24(1):205. doi: 10.1186/s13059-023-03022-8.

Authors

Barbara Poszewiecka^#¹, Krzysztof Gogolewski^#², Justyna A Karolak^{3

4}, Paweł Stankiewicz^#⁵, Anna Gambin^#⁶

Affiliations

¹ Faculty of Mathematics, Informatics, and Mechanics, University of Warsaw, Banacha 2, 02-097, Warsaw, Poland. b.poszewiecka@mimuw.edu.pl.
² Faculty of Mathematics, Informatics, and Mechanics, University of Warsaw, Banacha 2, 02-097, Warsaw, Poland. k.gogolewski@mimuw.edu.pl.
³ Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA.
⁴ Chair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, 60-806, Poznan, Poland.
⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA. pawels@bcm.edu.
⁶ Faculty of Mathematics, Informatics, and Mechanics, University of Warsaw, Banacha 2, 02-097, Warsaw, Poland.

^# Contributed equally.

Abstract

Resolving complex genomic regions rich in segmental duplications (SDs) is challenging due to the high error rate of long-read sequencing. Here, we describe a targeted approach with a novel genome assembler PhaseDancer that extends SD-rich regions of interest iteratively. We validate its robustness and efficiency using a golden-standard set of human BAC clones and in silico-generated SDs with predefined evolutionary scenarios. PhaseDancer enables extension of the incomplete complex SD-rich subtelomeric regions of Great Ape chromosomes orthologous to the human chromosome 2 (HSA2) fusion site, informing a model of HSA2 formation and unravelling the evolution of human and Great Ape genomes.

Keywords: Chromosomal fusion; Complex genomic rearrangements; De-novo assembly; Long-read PacBio sequencing; Segmental duplications.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chromosomes, Human
Genomics
Hominidae* / genetics
Humans
Segmental Duplications, Genomic
Telomere