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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.

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Abbreviations

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)

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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).

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Correspondence to Matthew Breen.

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Responsible Editor: Herbert Macgregor

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Supplemental Fig. 1

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)

High Resolution Image (EPS 6343 kb)

Supplemental Table 1–4

CFA regions corresponding to ECCSs are listed with the corresponding regions of red fox (VVU), Chinese raccoon dog (NPRp), and gray fox (UCI) indicated. Table 1 is sorted by dog region, Table 2 by red fox chromosome locations, Table 3 by Chinese raccoon dog chromosome locations, and Table 4 by gray fox chromosome locations. Regions with additional hybridization to B chromosomes of red fox and Chinese raccoon dog are noted with asterisks. While we used the nomenclature of Wayne et al. (1987a) for gray fox chromosomes, the final column lists the nomenclature used in Graphodatsky et al. (2008). The gray fox cells described in Graphodatsky et al. (2008) contain a translocation relative to the cells described in this text. The regions involved (CFA7, 28, 37 ECCSs on UCI12, 15) are noted with double asterisks here, shown in Fig. 4 and discussed in the text (XLS 47 kb)

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Duke Becker, S.E., Thomas, R., Trifonov, V.A. et al. 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. Chromosome Res 19, 685–708 (2011). https://doi.org/10.1007/s10577-011-9233-4

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