Species-wide distribution of highly polymorphic minisatellite markers suggests past and present genetic exchanges among house mouse subspecies

Abstract

Background: Four hypervariable minisatellite loci were scored on a panel of 116 individuals of various geographical origins representing a large part of the diversity present in house mouse subspecies. Internal structures of alleles were determined by minisatellite variant repeat mapping PCR to produce maps of intermingled patterns of variant repeats along the repeat array. To reconstruct the genealogy of these arrays of variable length, the specifically designed software MS_Align was used to estimate molecular divergences, graphically represented as neighbor-joining trees.

Results: Given the high haplotypic diversity detected (mean He = 0.962), these minisatellite trees proved to be highly informative for tracing past and present genetic exchanges. Examples of identical or nearly identical alleles were found across subspecies and in geographically very distant locations, together with poor lineage sorting among subspecies except for the X-chromosome locus MMS30 in Mus mus musculus. Given the high mutation rate of mouse minisatellite loci, this picture cannot be interpreted only with simple splitting events followed by retention of polymorphism, but implies recurrent gene flow between already differentiated entities.

Conclusion: This strongly suggests that, at least for the chromosomal regions under scrutiny, wild house mouse subspecies constitute a set of interrelated gene pools still connected through long range gene flow or genetic exchanges occurring in the various contact zones existing nowadays or that have existed in the past. Identifying genomic regions that do not follow this pattern will be a challenging task for pinpointing genes important for speciation.

Figure 1

Geographical location of the localities sampled. 1, Lake Casitas, CA, USA; 2, Azzemour, Morocco; 3, Ouarzazate, Morocco; 4, Azrou, Morocco; 5, Leo'n prov., Spain; 6, Granada, Spain; 7, Oran, Algeria; 8, Ardèche, France; 9, Montpellier, France 10, Monastir, Bembla, M'saken, Tunisia; 11, Sfax, Tunisia; 12, Cascina Orcetto, Italy; 13, Ödis, Denmark; 14, Hov, Denmark; 15, Bohemia reg., Czech Republic; 16, Bialowieza, Poland; 17, Kranevo, Sokolovo, Bulgaria; 18, Vlas, Bulgaria; 19, Moscow, Russia; 20, Abkhasia prov., Georgia; 21, Adjaria prov., Georgia; 22, Van Lake, Turkey; 23, KefarGalim, Israel; 24, Cairo, Egypt; 25, Megri, Armenia; 26, Alazani, Chirackskaya, DidichChiraki, Gardabani, Lissi, Vachlavan, Tbilissi, Georgia; 27, Daghestan, Russia; 28, Antananarivo, Manakasina, Madagascar; 29, Mashhad, Kahkh, Birdjand, Iran; 30, Turkmenistan; 31, Gujarkhan, Islamabad, Tamapasabad, Rawalpindi, Pakistan; 32, Jalandhar, Bikaner, Delhi, India; 33, Pachmarhi, India; 34, Masinagudi, India; 35, Varanasi, India; 36, Gauhati, India; 37, PathumThani, Thailand; 38, Gansu prov., China; 39, Fuhai, China; 40, Taiwan; 41, Mishima, Japan; 42, Tahiti, French Polynesia.

Figure 2

Maps of the internal structure of variant repeats for mouse minisatellite MMS24. Groups of similar haplotypes were chosen arbitrarily for the purpose of illustrating the maps' complexity. The groups correspond to clades in the trees of Figure 7. Their maps were aligned with the multiple alignment procedure MS_Alimul (E Rivals, unpublished) and the alignments edited manually. Under an alignment column, an asterisk indicates a complete conservation, while a period means that 60% of the variants in the column are identical. The alignments show which type of mutations occur between alleles, and where corresponding differences are located in the maps. For comparison, we also display for each locus one of the shortest and one of the longest or most complex alleles. Color code: spretus, orange; domesticus, blue; castaneus/cen, red; musculus, green.

Figure 3

Maps of the internal structure of variant repeats for mouse minisatellite MMS26. Groups of similar haplotypes were chosen arbitrarily for the purpose of illustrating the maps' complexity. The groups correspond to clades in the trees of Figure 7. Their maps were aligned with the multiple alignment procedure MS_Alimul (E Rivals, unpublished) and the alignments edited manually. Under an alignment column, an asterisk indicates a complete conservation, while a period means that 60% of the variants in the column are identical. The alignments show which type of mutations occur between alleles, and where corresponding differences are located in the maps. For comparison, we also display for each locus one of the shortest and one of the longest or most complex alleles. Color code: spretus, orange; domesticus, blue; castaneus/cen, red; musculus, green.

Figure 4

Maps of the internal structure of variant repeats for mouse minisatellite MMS30. For this locus, the alignments of domesticus haplotypes also comprise 4 CAS/CEN haplotypes. These castaneus and central haplotypes are clearly more similar to the domesticus alleles than to the group of CAS/CEN alleles in the top multiple alignment. The sequence motifs shared between these introgressed CAS/CEN haplotypes and the domesticus and/or the musculus haplotypes are shown in bold in a few maps. Groups of similar haplotypes were chosen arbitrarily for the purpose of illustrating the maps' complexity. The groups correspond to clades in the trees of Figure 7. Their maps were aligned with the multiple alignment procedure MS_Alimul (E Rivals, unpublished) and the alignments edited manually. Under an alignment column, an asterisk indicates a complete conservation, while a period means that 60% of the variants in the column are identical. The alignments show which type of mutations occur between alleles, and where corresponding differences are located in the maps. For comparison, we also display for each locus one of the shortest and one of the longest or most complex alleles. Color code: spretus, orange; domesticus, blue; castaneus/cen, red; musculus, green.

Figure 5

Maps of the internal structure of variant repeats for mouse minisatellite MMS80. Groups of similar haplotypes were chosen arbitrarily for the purpose of illustrating the maps' complexity. The groups correspond to clades in the trees of Figure 7. Their maps were aligned with the multiple alignment procedure MS_Alimul (E Rivals, unpublished) and the alignments edited manually. Under an alignment column, an asterisk indicates a complete conservation, while a period means that 60% of the variants in the column are identical. The alignments show which type of mutations occur between alleles, and where corresponding differences are located in the maps. For comparison, we also display for each locus one of the shortest and one of the longest or most complex alleles. Color code: spretus, orange; domesticus, blue; castaneus/cen, red; musculus, green.

Figure 6

Most reliable coalescence obtained at locus MMS24. Neighbor-joining trees obtained from the matrices of allele alignment distances computed with the MS_Align pairwise alignment program [9]. For each internal edge, the corresponding confidence value Re (in the range [0,100]) is shown. The clades referred to by roman letters in parentheses in the text are indicated.

Figure 7

Most reliable coalescence obtained at locus MMS26. Neighbor-joining trees obtained from the matrices of allele alignment distances computed with the MS_Align pairwise alignment program [9]. For each internal edge, the corresponding confidence value Re (in the range [0,100]) is shown. The clades referred to by roman letters in parentheses in the text are indicated.

Figure 8

Most reliable coalescence obtained at locus MMS30. Neighbor-joining trees obtained from the matrices of allele alignment distances computed with the MS_Align pairwise alignment program [9]. For each internal edge, the corresponding confidence value Re (in the range [0,100]) is shown. The clades referred to by roman letters in parentheses in the text are indicated.

Figure 9

Most reliable coalescence obtained at locus MMS80. Neighbor-joining trees obtained from the matrices of allele alignment distances computed with the MS_Align pairwise alignment program [9]. For each internal edge, the corresponding confidence value Re (in the range [0,100]) is shown. The clades referred to by roman letters in parentheses in the text are indicated.