Anchoring the dog to its relatives reveals new evolutionary breakpoints across 11 species of the Canidae and provides new clues for the role of B chromosomes
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Abstract
The emergence of genome-integrated molecular cytogenetic resources allows for comprehensive comparative analysis of gross karyotype architecture across related species. The identification of evolutionarily conserved chromosome segment (ECCS) boundaries provides deeper insight into the process of chromosome evolution associated with speciation. We evaluated the genome-wide distribution and relative orientation of ECCSs in three wild canid species with diverse karyotypes (red fox, Chinese raccoon dog, and gray fox). Chromosome-specific panels of dog genome-integrated bacterial artificial chromosome (BAC) clones spaced at ∼10-Mb intervals were used in fluorescence in situ hybridization analysis to construct integrated physical genome maps of these three species. Conserved evolutionary breakpoint regions (EBRs) shared between their karyotypes were refined across these and eight additional wild canid species using targeted BAC panels spaced at ∼1-Mb intervals. Our findings suggest that the EBRs associated with speciation in the Canidae are compatible with recent phylogenetic groupings and provide evidence that these breakpoints are also recurrently associated with spontaneous canine cancers. We identified several regions of domestic dog sequence that share homology with canid B chromosomes, including additional cancer-associated genes, suggesting that these supernumerary elements may represent more than inert passengers within the cell. We propose that the complex karyotype rearrangements associated with speciation of the Canidae reflect unstable chromosome regions described by the fragile breakage model.
Keywords
B chromosomes fragile breakage model breakpoint reuse theory fluorescence in situ hybridization phylogenetic CanidaeAbbreviations
- BAC
Bacterial artificial chromosome
- BLAST
Basic local alignment search tool
- CBR
Chrysocyon brachyurus (maned wolf)
- CFA
Canis familiaris (domestic dog)
- CHORI
Children’s Hospital Oakland Research Institute
- cKIT
Cellular homolog for feline sarcoma viral oncogene vKIT
- CTH
Cerdocyon thous (crab-eating fox)
- DNA
Deoxyribonucleic acid
- DVE
Dusicyon vetulus (hoarey fox)
- EBR
Evolutionary breakpoint region
- ECCS
Evolutionarily conserved chromosomal segment
- FBM
Fragile breakage model
- FISH
Fluorescence in situ hybridization
- FZE
Fennecus zerda (fennec fox)
- LRIG1
Leucine-rich repeats and immunoglobulin-like domain protein 1
- NPRp
Nyctereutes procynoides procynoides (Chinese raccoon dog)
- NPRv
Nyctereutes procynoides viverrinus (Japanese raccoon dog)
- OME
Otocyon megalotis (bat-eared fox)
- RET
Rearranged during transfection
- SA
South American
- SVE
Speothus venaticus (bush dog)
- UCI
Urocyon cinereogenteus (gray fox)
- VMA
Vulpes macrotis (kit fox)
- VVU
Vulpes vulpes (red fox)
Notes
Acknowledgments
This study was supported by a grant from the Morris Animal Foundation awarded to MB (D08ZO-022). SEDB was funded in part by the Comparative Biomedical Sciences Graduate Program at NCSU. RW was supported by funds from the National Science Foundation (DEB0614585), and ASG and VAT were supported by funds from the Program on Molecular and Cellular Biology (MCB) and Russian Foundation of Basic Research (RFBR).
Supplementary material
a Thirteen BAC probes spaced ∼10 Mb apart along the length of CFA1 were hybridized together onto CFA chromosome spreads. The location and orientation of the panel represents the CFA1 ECCS. b The CFA1 probe panel was hybridized to VVU5 and VVU1, revealing a breakpoint between probes representing CFA1;22.3 Mb (yellow) and CFA1;32. 3Mb (purple). Regions of CFA1 ECCSs on either side of the breakpoint are indicated with a suffix (i.e., CFA1a and CFA1b). Through application of the multicolor labeling strategy, the location and orientation of each CFA1 ECCS was evident (inset). Scale bar, 10 μm (JPEG 2026 kb)
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