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Evolution of Mouse Major Histocompatibility Complex Genes Borne by T Chromosomes (Class II Genes/T Complex/Restriction Fragments/Polymorphism)

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Evolution of Mouse Major Histocompatibility Complex Genes Borne by T Chromosomes (Class II Genes/T Complex/Restriction Fragments/Polymorphism) Proc. Natl. Acad. Sci. USA Vol. 82, pp. 2819-2823, May 1985 Evolution Evolution of mouse major histocompatibility complex genes borne by t chromosomes (class II genes/t complex/restriction fragments/polymorphism) FELIPE FIGUEROA, MLADEN GOLUBI(*, DEAN NIETI(*, AND JAN KLEIN Max-Planck-Institut fur Biologie, Abteilung Immungenetik, Corrensstrasse 42, 7400 Tubingen, Federal Republic of Germany Communicated by Ray D. Owen, December 26, 1984 ABSTRACT Virtually all wild mouse populations carry t H-2 genes are highly polymorphic and hence can be used to haplotypes that cause embryonic lethality or semilethality, differentiate chromosomes (8). On the t chromosomes, the distortion of segregation ratios, suppression of crossing-over, H-2 complex is included in the region of suppressed cross- and male sterility. The t complex of genes is located on ing-over and it is therefore ideally suited for tracing the origin chromosome 17, closely linked to the H-2, the major histocom- of t haplotypes. In a previous study, we used serology of the patibility complex of the mouse. The t haplotypes differ from H-2 antigens as a tool to determine the degree of relatedness each other not only in lethal genes they carry but also in their among the different t haplotypes (9, 10). In this report, we linked H-2 haplotypes. In this study, we compared the class II applied the genomic Southern blot hybridization technique to H-2 genes present on 31 t chromosomes extracted from wild the class II genes of the H-2 complex carried by the different populations in different parts ofthe world. The comparison was t chromosomes. The combination of these two approaches based on the analysis of DNA fragments obtained after diges- provides a glimpse into the t complex genealogy. tion with restriction endonucleases. The results reveal the existence of three major groups of class II alleles representing MATERIALS AND METHODS main branches on the evolutionary tree of the t chromosomes. Alleles within each group are similar if not identical, although Materials. Proteinase K, DNA molecular weight markers, they are borne by chromosomes that have been separated in ribonucleases, and restriction endonucleases were purchased time and space. The presence of similar alleles in Mus musculus from Boehringer (Mannheim, F.R.G.), blotting materials and Mus domesticus suggests that some of them may have been were from Bethesda Research Laboratories (Neu Isenburg, separated for more than 1 million years. This must also be the F.R.G.), the nick-translation kit was from Amersham Inter- minimal age of the t chromosomes but, because at least two of national (Braunschweig, F.R.G.), and [a-32P]dCTP was from the three main branches appear to be related in their origin, the New England Nuclear (Dreieich, F.R.G.). actual age of t chromosomes could be much greater. The Mice. All mice came from our animal colony at the Max observations support the proposal that H-2 genes evolve slowly. Planck Institute for Biology. The strains carrying new t haplotypes were established in our laboratory from wild mice Some matings between wild mice and laboratory strains trapped at the locations listed in Table 1 (6, 9, 10). carrying the dominant mutation short tail, T, invariably DNA Isolation. DNA was isolated from kidney cells. Six to produce tailless progeny. The absence of the tail is attributed eight kidneys were cut into small pieces, which were then to the interaction between T and another mutation, t, which pressed through a sieve (no. 1985-00050, Technorame, occurs in some wild mouse populations with a frequency of Zurich, Switzerland). The cells were washed twice, resus- up to 40% (1). The t mutation affects, in addition to tail length, pended in Tris/saline, pH 8.0, containing proteinase K and several other characteristics (2-5). The t/t embryos may all NaDodSO4, and the suspension was incubated overnight at die (lethal t) or some may die while others survive (semilethal 450C. The incubation was followed by phenol/chloroform t). Only rarely does one find fully viable t haplotypes among extraction, RNase treatment, and ethanol precipitation. wild mice (6), although in the laboratory they can arise from Digestion with Restriction Endonucleases. The high molecu- the lethal haplotypes by recombination. In the +/It mice the lar weight DNA was diluted in the appropriate buffer and lethal or semilethal t haplotypes suppress crossing-over over incubated overnight with the selected restriction endonucle- a distance of at least 15 centimorgans, cause male sterility, ase at the required temperature. A proportion of 6 units of and skew segregation ofthe t chromosome transmitted by the enzyme per 1 ,g of DNA was used. male. At least some of these characteristics are controlled by Southern Blot Hybridization. Electrophoresis of the di- different genes that are locked together into a single unit, the gested DNA was done in a 0.8% agarose gel at 30 mA for t the The about 30 hr. The DNA was then transferred to nitrocellulose complex, by crossing-over suppressor. different t filters (11). The blots were baked, prehybridized for 4-5 hr at haplotypes are distinguished mainly by the type of lethal 42°C, and hybridized with 32P-labeled probes in a solution genes they carry. containing 50% formamide, 0.6 M NaCl/0.06 M sodium Among the many unanswered questions about the t com- citrate, lx concentrated Denhardt's solution, sodium phos- plex, the most fascinating is how did the t haplotypes arise. phate buffer (pH 6.5), 10% dextran sulfate, and salmon sperm As the products of most of the t genes have not been DNA. The filters were washed three times (two times for 20 identified, it is not possible to answer this question by the min in 0.3 M NaCl/0.03 M sodium citrate/0.1% NaDodSO4 at direct study of the t haplotypes. However, linked to the t 48°C and one time for 20 min in 15 mM NaCl/1.5 mM sodium complex on chromosome 17 is the H-2 complex, which codes citrate/0.1% NaDodSO4 at 52°C). Autoradiographs of the for plasma membrane glycoproteins involved in the recogni- blots were prepared by using Kodak XS1 film with a Lanex tion of foreign antigens by T lymphocytes (7). Some of the intensifier screen. The films were exposed for 16-48 hr. The publication costs of this article were defrayed in part by page charge Abbreviation: kb, kilobase(s). payment. This article must therefore be hereby marked "advertisement" *On leave from the Department of Physiology, University of Zagreb in accordance with 18 U.S.C. §1734 solely to indicate this fact. Medical Faculty, Zagreb, Yugoslavia. 2819 Downloaded by guest on September 25, 2021 2820 Evolution: Figueroa et al. Proc. Natl. Acad. Sci. USA 82 (1985) Table 1. Strains carrying t haplotypes tested in the present study each experiment. The DNA was then digested with restric- t H-2 tion nucleases and the fragments were hybridized with Ap- haplo- t haplo- and Ep-specific probes. Six restriction enzymes were used type Strain Origin group type (EcoRI, HindIII, Xba I, Sac I, BamHI, BstEII, Alu I, Hae IIIB, and Taq I) but not all of the samples were digested with t6 Laboratory 0 all of these enzymes. tw1 - New York or Phila- wI The patterns obtained are shown in Figs. 1 and 2. We have delphia, U.S.A. designated them by letters a, b, c, and so on (see Tables 2 and tuwll GPC882 Buin, Chile Tuwll w30 3). An asterisk indicates that an additional band is contrib- tTuw15 MOY336 Moya, Spain Tuwl2 w65 Alpic Drobic, Italy uted by the non-t chromosome and that we could not decide tLubl Lubi w33 whether a similar band is also contributed by the t chromo- tTuwl2 LRA410 La Roca, Spain Tuwl2 w66 some. Based on the different patterns, the t strains can be tLub4 - Cremona, Italy Lubi, Lub4 w64 Calcinato, Italy divided into four groups, which we designate I through IV. tLub9 Lub4 w64 The Ap3 group I (Table 2) consists of 13 strains, 8 of which tTuw32 ISL33 Haifa, Israel V w56 yielded identical restriction patterns, while 5 (tw73, KPB68, tTuw30 B10.KPB68 Ann Arbor, MI, SL w2 EDY589, ISL37, and ISL33) produced variants of the basic U.S.A. pattern. We designate the basic allele Ad30 and differentiate tTuw18 ISL37 Haifa, Israel SL w2 the variants by additional numbers following the decimal tTuwlO EDY589 Eday, Orkney Is- SL w2 point. The An group II consists of 8 strains, of which all, lands except CR0435 (one difference), yielded identical restriction tw73 S. Jutland, Den- w73 w32 patterns (allele Aw36). The Ag3 group III consists of 5 strains, mark 4 of which yielded identical patterns (allele A 31), although tTuw26 PLD826 Bialowieza, Poland w73 w59 the CR0437 and the Lub7 strains could be distinguished tTuw2 BNK266 Wendelsheim, Tuw2, Tuw25 w36 serologically by their loci (10). The BRU382 strain produced F.R.G. a variant of the basic pattern. The An group IV contains 5 tTuw2l BNK761 Wendelsheim, Tuw2, Tuw25 w36 strains that do not fit into any of the previous groups and F.R.G. whose relationships to one another are not obvious. How- tTuw25 OBL984 Oberer Lindenhof, Tuw25 w36 ever, serological analysis suggests that their Aq3 genes (with F.R.G. the exception of BRW942) are related to the A430 allele (10). tTuw27 ROD1455 Dudelhof, F.R.G. Tuw27 w36 The En group I contains the same strains as the Ad group tTuw24 LGN925 Langenargen, Tuw24 w36 I (Table 3). All of these strains, with the exception of ISL33, F.R.G.
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