Recombination between heterologous human acrocentric chromosomes
Authors: Guarracino Andrea , Buonaiuto Silvia , de Lima Leonardo Gomes , Potapova Tamara , Rhie Arang , Koren Sergey , Rubinstein Boris , Fischer Christian ,   Human Pangenome Reference Consortium, Abel Haley J. , Antonacci-Fulton Lucinda L. , Asri Mobin , Baid Gunjan , Baker Carl A. , Belyaeva Anastasiya , Billis Konstantinos , Bourque Guillaume , Carroll Andrew , Chaisson Mark J. P. , Chang Pi-Chuan , Chang Xian H. , Cheng Haoyu , Chu Justin , Cody Sarah , Cook Daniel E. , Cook-Deegan Robert M. , Cornejo Omar E. , Diekhans Mark , Doerr Daniel , Ebert Peter , Ebler Jana , Eichler Evan E. , Eizenga Jordan M. , Fairley Susan , Fedrigo Olivier , Felsenfeld Adam L. , Feng Xiaowen , Flicek Paul , Formenti Giulio , Frankish Adam , Fulton Robert S. , Gao Yan , Garg Shilpa , Garrison Nanibaa’ A. , Giron Carlos Garcia , Green Richard E. , Groza Cristian , Haggerty Leanne , Hall Ira , Harvey William T. , Haukness Marina , Haussler David , Heumos Simon , Hickey Glenn , Hoekzema Kendra , Hourlier Thibaut , Howe Kerstin , Jain Miten , Jarvis Erich D. , Ji Hanlee P. , Kenny Eimear E. , Koenig Barbara A. , Kolesnikov Alexey , Korbel Jan O. , Kordosky Jennifer , Lee HoJoon , Lewis Alexandra P. , Li Heng , Liao Wen-Wei , Lu Shuangjia , Lu Tsung-Yu , Lucas Julian K. , Magalhães Hugo , Marco-Sola Santiago , Marijon Pierre , Markello Charles , Marschall Tobias , Martin Fergal J. , McCartney Ann , McDaniel Jennifer , Miga Karen H. , Mitchell Matthew W. , Monlong Jean , Mountcastle Jacquelyn , Munson Katherine M. , Mwaniki Moses Njagi , Nattestad Maria , Novak Adam M. , Nurk Sergey , Olsen Hugh E. , Olson Nathan D. , Paten Benedict , Pesout Trevor , Popejoy Alice B. , Porubsky David , Prins Pjotr , Puiu Daniela , Rautiainen Mikko , Regier Allison A. , Sacco Samuel , Sanders Ashley D. , Schneider Valerie A. , Schultz Baergen I. , Shafin Kishwar , Sibbesen Jonas A. , Sirén Jouni , Smith Michael W. , Sofia Heidi J. , Tayoun Ahmad N. Abou , Thibaud-Nissen Françoise , Tomlinson Chad , Tricomi Francesca Floriana , Villani Flavia , Vollger Mitchell R. , Wagner Justin , Walenz Brian , Wang Ting , Wood Jonathan M. D. , Zimin Aleksey V. , Zook Justin M. , Gerton Jennifer L. , Phillippy Adam M. , Colonna Vincenza , Garrison Erik 
Published: May 2023

AbstractThe short arms of the human acrocentric chromosomes 13, 14, 15, 21 and 22 (SAACs) share large homologous regions, including ribosomal DNA repeats and extended segmental duplications1,2. Although the resolution of these regions in the first complete assembly of a human genome—the Telomere-to-Telomere Consortium’s CHM13 assembly (T2T-CHM13)—provided a model of their homology3, it remained unclear whether these patterns were ancestral or maintained by ongoing recombination exchange. Here we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologous sequences. Utilizing an all-to-all comparison of the human pangenome from the Human Pangenome Reference Consortium4 (HPRC), we find that contigs from all of the SAACs form a community. A variation graph5 constructed from centromere-spanning acrocentric contigs indicates the presence of regions in which most contigs appear nearly identical between heterologous acrocentric chromosomes in T2T-CHM13. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the pseudo-homologous regions than in the corresponding short and long arms, indicating higher rates of recombination6,7. The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations8, and their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14 and 21. The ubiquity of signals of recombination between heterologous acrocentric chromosomes seen in the HPRC draft pangenome suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed from cytogenetic studies 50 years ago9.