Evolution of the ancestral mammalian karyotype and syntenic regions
Authors: Damas Joana , Corbo Marco , Kim Jaebum , Turner-Maier Jason , Farré Marta , Larkin Denis M. , Ryder Oliver A. , Steiner Cynthia , Houck Marlys L. , Hall Shaune , Shiue Lily , Thomas Stephen , Swale Thomas , Daly Mark , Korlach Jonas , Uliano-Silva Marcela , Mazzoni Camila J. , Birren Bruce W. , Genereux Diane P. , Johnson Jeremy , Lindblad-Toh Kerstin , Karlsson Elinor K. , Nweeia Martin T. , Johnson Rebecca N. ,   Zoonomia Consortium, Lewin Harris A. , Andrews Gregory , Armstrong Joel C. , Bianchi Matteo , Birren Bruce W. , Bredemeyer Kevin R. , Breit Ana M. , Christmas Matthew J. , Clawson Hiram , Damas Joana , Palma Federica Di , Diekhans Mark , Dong Michael X. , Eizirik Eduardo , Fan Kaili , Fanter Cornelia , Foley Nicole M. , Forsberg-Nilsson Karin , Garcia Carlos J. , Gatesy John , Gazal Steven , Genereux Diane P. , Goodman Linda , Grimshaw Jenna , Halsey Michaela K. , Harris Andrew J. , Hickey Glenn , Hiller Michael , Hindle Allyson G. , Hubley Robert M. , Hughes Graham M. , Johnson Jeremy , Juan David , Kaplow Irene M. , Karlsson Elinor K. , Keough Kathleen C. , Kirilenko Bogdan , Koepfli Klaus-Peter , Korstian Jennifer M. , Kowalczyk Amanda , Kozyrev Sergey V. , Lawler Alyssa J. , Lawless Colleen , Lehmann Thomas , Levesque Danielle L. , Lewin Harris A. , Li Xue , Lind Abigail , Lindblad-Toh Kerstin , Mackay-Smith Ava , Marinescu Voichita D. , Marques-Bonet Tomas , Mason Victor C. , Meadows Jennifer R. S. , Meyer Wynn K. , Moore Jill E. , Moreira Lucas R. , Moreno-Santillan Diana D. , Morrill Kathleen M. , Muntané Gerard , Murphy William J. , Navarro Arcadi , Nweeia Martin , Ortmann Sylvia , Osmanski Austin , Paten Benedict , Paulat Nicole S. , Pfenning Andreas R. , Phan BaDoi N. , Pollard Katherine S. , Pratt Henry E. , Ray David A. , Reilly Steven K. , Rosen Jeb R. , Ruf Irina , Ryan Louise , Ryder Oliver A. , Sabeti Pardis C. , Schäffer Daniel E. , Serres Aitor , Shapiro Beth , Smit Arian F. A. , Springer Mark , Srinivasan Chaitanya , Steiner Cynthia , Storer Jessica M. , Sullivan Kevin A. M. , Sullivan Patrick F. , Sundström Elisabeth , Supple Megan A. , Swofford Ross , Talbot Joy-El , Teeling Emma , Turner-Maier Jason , Valenzuela Alejandro , Wagner Franziska , Wallerman Ola , Wang Chao , Wang Juehan , Weng Zhiping , Wilder Aryn P. , Wirthlin Morgan E. , Xue James R. , Zhang Xiaomeng 
Published: September 2022

Decrypting the rearrangements that drive mammalian chromosome evolution is critical to understanding the molecular bases of speciation, adaptation, and disease susceptibility. Using 8 scaffolded and 26 chromosome-scale genome assemblies representing 23/26 mammal orders, we computationally reconstructed ancestral karyotypes and syntenic relationships at 16 nodes along the mammalian phylogeny. Three different reference genomes (human, sloth, and cattle) representing phylogenetically distinct mammalian superorders were used to assess reference bias in the reconstructed ancestral karyotypes and to expand the number of clades with reconstructed genomes. The mammalian ancestor likely had 19 pairs of autosomes, with nine of the smallest chromosomes shared with the common ancestor of all amniotes (three still conserved in extant mammals), demonstrating a striking conservation of synteny for ∼320 My of vertebrate evolution. The numbers and types of chromosome rearrangements were classified for transitions between the ancestral mammalian karyotype, descendent ancestors, and extant species. For example, 94 inversions, 16 fissions, and 14 fusions that occurred over 53 My differentiated the therian from the descendent eutherian ancestor. The highest breakpoint rate was observed between the mammalian and therian ancestors (3.9 breakpoints/My). Reconstructed mammalian ancestor chromosomes were found to have distinct evolutionary histories reflected in their rates and types of rearrangements. The distributions of genes, repetitive elements, topologically associating domains, and actively transcribed regions in multispecies homologous synteny blocks and evolutionary breakpoint regions indicate that purifying selection acted over millions of years of vertebrate evolution to maintain syntenic relationships of developmentally important genes and regulatory landscapes of gene-dense chromosomes.