Distorter genes of the mouse t-complex impair male fertility when heterozygous

SummaryMale mice heterozygous for two distorter genes, Tcd-1 and Tcd-2, of the mouse t-complex but homozygous wild type for the responder, were generated by crossing animals carrying the partial t-haplotypes th51 and th18 to inbred strains. The fertility of these males was then compared with that of their brothers carrying normal chromosome 17s. On three of the inbred backgrounds used, C3H/HeH, C57BL/6J and TFH/H, the th51th18 + / + + + males were significantly less fertile than their normal sibs. With the fourth inbred strain used, SM/JH, both types of male were nonnally fertile. This confirmed earlier preliminary findings that when both homologues of chromosome 17 carry wild-type alleles of the responder, heterozygosity for the distorter genes is sufficient to impair fertility, but the effect varies with genetic background. These results are consistent with the concept that both the transmission ratio distortion and the male sterility caused by the t-complex are due to harmful effects of the distorter genes on wild-type alleles of the responder.

Download Full-text

Genetic exchange across a paracentric inversion of the mouse t complex.

Genetics ◽

10.1093/genetics/128.4.799 ◽

1991 ◽

Vol 128 (4) ◽

pp. 799-812 ◽

Cited By ~ 1

Author(s):

M F Hammer ◽

S Bliss ◽

L M Silver

Keyword(s):

Inbred Strains ◽

Genetic Exchange ◽

Transmission Ratio Distortion ◽

Chromosome 17 ◽

Wild Type ◽

T Complex ◽

Haplotype Allele ◽

Hybrid Allele ◽

Paracentric Inversions ◽

T Haplotype

Abstract Mouse t haplotypes are distinguished from wild-type forms of chromosome 17 by four nonoverlapping paracentric inversions which span a genetic distance of 20 cM. These inversion polymorphisms are responsible for a 100-200-fold suppression of recombination which maintains the integrity of complete t haplotypes and has led to their divergence from the wild-type chromosomes of four species of house mice within which t haplotypes reside. As evidence for the long period of recombinational isolation, alleles that distinguish all t haplotypes from all wild-type chromosomes have been established at a number of loci spread across the 20-cM variant region. However, a more complex picture emerges upon analysis of other t-associated loci. In particular, "mosaic haplotypes" have been identified that carry a mixture of wild-type and t-specific alleles. To investigate the genetic basis for mosaic chromosomes, we conducted a comprehensive analysis of eight t complex loci within 76 animals representing 10 taxa in the genus Mus, and including 23 previously characterized t haplotypes. Higher resolution restriction mapping and sequence analysis was also performed for alleles at the Hba-ps4 locus. The results indicate that a short tract of DNA was transferred relatively recently across an inversion from a t haplotype allele of Hba-ps4 to the corresponding locus on a wild-type homolog leading to the creation of a new hybrid allele. Several classes of wild-type Hba-ps4 alleles, including the most common form in inbred strains, appear to be derived from this hybrid allele. The accumulated data suggest that a common form of genetic exchange across one of the four t-associated inversions is gene conversion at isolated loci that do not play a role in the transmission ratio distortion phenotype required for t haplotype propagation. The implications of the results pose questions concerning the evolutionary stability of gene complexes within large paracentric inversions and suggest that recombinational isolation may be best established for loci residing within a short distance from inversion breakpoints.

Download Full-text

Search for differences among t haplotypes in distorter and responder genes

Genetics Research ◽

10.1017/s0016672300025143 ◽

1990 ◽

Vol 55 (1) ◽

pp. 13-19 ◽

Cited By ~ 14

Author(s):

Mary F. Lyon

Keyword(s):

Genetic Background ◽

Complex Form ◽

Transmission Ratio Distortion ◽

Transmission Ratio ◽

Naturally Occurring ◽

Harmful Action ◽

Ratio Distortion ◽

Harmful Effects

SummaryTransmission ratio distortion due to the mouse t complex is thought to be due to harmful effects of trans-acting distorter genes acting on a responder, with the t complex form of the responder being relatively resistant to this harmful action of the distorters. Previous work had indicated that naturally occurring t haplotypes differed in their responders or in distorters lying near the responder, with the result that animals doubly heterozygous for two responder-carrying haplotypes transmitted these haplotypes unequally. In the present work t haplotypes could be divided into three types on the basis of their transmission when doubly heterozygous with the responder-carrying partial haplotype tlowH. The majority, t0, t6, tw1, tw2 and tw73, were transmitted equally with tlowH, a second group, including tw5 and two haplotypes derived from it, were transmitted less frequently than tlowH, and the single member of a third group, t32, was transmitted in excess of tlowH This last result suggests that the underlying differences are in the responder itself, rather than in the distorters. Search for differences among t haplotypes in distorters produced some equivocal results possibly resulting from effects of genetic background. In particular, results of others suggesting presence of a fourth distorter, Tcd-4, were not confirmed.

Download Full-text

Recent evolution of mouse t haplotypes at polymorphic microsatellites associated with the t complex responder (Tcr) locus

Genetics Research ◽

10.1017/s0016672300033425 ◽

1996 ◽

Vol 67 (1) ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Kristin G. Ardlie ◽

Lee M. Silver

Keyword(s):

Field Studies ◽

Complementation Group ◽

Transmission Ratio Distortion ◽

Chromosome 17 ◽

Recent Common Ancestor ◽

Central Component ◽

Wild Mice ◽

T Complex ◽

Founding Population ◽

Ratio Distortion

SummaryMicrosatellites closely associated with each member of the Tcp1O gene family were amplified simultaneously from t haplotype and wild-type forms of mouse chromosome 17, by PCR. The t complex responder (Tcr) locus, which plays a central role in transmission ratio distortion, maps within the Tcp10 cluster on the t haplotype. Thus the amplified set of microsatellite loci (referred to collectively as Tcp10ms) provides a direct marker for this central component of the meiotic drive system associated with all naturally occurring t haplotypes. A unique Tcp10ms pattern of microsatellite alleles was obtained for a number of independent, laboratory-maintained complete and partial t haplotypes. Independent t chromosomes found in wild mice from US populations also had unique patterns, even when they were classified within the same lethal complementation group. Wild and laboratory chromosomes in the tw5 group showed similarly-sized but non-identical Tcp10ms patterns, suggesting they share a recent common ancestor. These chromosomes are likely to have derived from an ancestral chromosome within the founding population of North American house mice. The Tcp10ms pattern was also shown to be useful in field studies for distinguishing among independentt haplotypes, when more than one is present within a single population.

Download Full-text

Differences in or near the responder region of complete and partial mouse t-haplotypes

Genetics Research ◽

10.1017/s0016672300023302 ◽

1987 ◽

Vol 50 (1) ◽

pp. 29-34 ◽

Cited By ~ 15

Author(s):

Mary F. Lyon ◽

Joanna Zenthon

Keyword(s):

Harmful Effect ◽

Complex Form ◽

Transmission Ratio Distortion ◽

Wild Type ◽

Homologous Chromosomes ◽

Cis Acting ◽

Ratio Distortion ◽

Lower Transmission ◽

In Cis ◽

Harmful Effects

SummaryThe transmission ratio distortion seen in males heterozygous for a mouse t-complex has been explained on the basis of trans-acting distorter genes, having a harmful effect on a responder gene. The t-complex form of the responder is relatively resistant to these harmful effects and hence is preferentially transmitted. Animals homozygous for the t-complex responder would be expected to show equal transmission of the two homologous chromosomes, but this is not always so. Studies described in this paper have shown differences among complete t's in their transmission when opposite a constant responder carrying partial t-haplotype. In addition, the proximal partial haplotypes th49 and tw18, both derived from tw5 but of different lengths, behave differently when opposite a responder. The three central partial haplotypes, tlowH, tlow2H and tlow3H, also differ, in that tlow3H shows lower transmission than tlowH or tloW2H when opposite either wild-type, or another responder, or distorter genes. These results can be explained either on the basis of differences in the responder region of various haplotypes, including the possibility of varying numbers of copies of the relevant sequences, or on the basis of differences in cis-acting (as opposed to trans-acting) distorter genes.

Download Full-text

Deletion analysis of male sterility effects of t–haplotypes in the mouse

Genetics Research ◽

10.1017/s0016672300035278 ◽

1990 ◽

Vol 56 (2-3) ◽

pp. 179-183 ◽

Cited By ~ 4

Author(s):

Dorothea Bennett ◽

Karen Artzt

Keyword(s):

Male Sterility ◽

Deletion Analysis ◽

Transmission Ratio Distortion ◽

Chromosome 17 ◽

Transmission Ratio ◽

Wild Type ◽

Ratio Distortion ◽

Very High

SummaryWe present data on the effects of three chromosome 17 deletions on transmission ratio distortion (TRD) and sterility of several t-haplotypes. All three deletions have similar effects on male TRD: that is, Tdel/tcomplete genotypes all transmit their t–haplotype in very high proportion. However, each deletion has different effects on sterility of heterozygous males, with Tor/t being fertile, Thp/t less fertile, and Torl/t still less fertile. These data suggest that wild-type genes on chromosomes homologous to f-haplotypes can be important regulators of both TRD and fertility in males, and that the wild-type genes concerned with TRD and fertility are at least to some extent different. The data also provide a rough map of the positions of these genes.

Download Full-text

THE INFLUENCE OF GENETIC BACKGROUND AND THE HOMOLOGOUS CHROMOSOME 17 ON t-HAPLOTYPE TRANSMISSION RATIO DISTORTION IN MICE

Genetics ◽

10.1093/genetics/114.1.235 ◽

1986 ◽

Vol 114 (1) ◽

pp. 235-245

Author(s):

Gregory R Gummere ◽

Paulette J McCormick ◽

Dorothea Bennett

Keyword(s):

Genetic Background ◽

Homologous Chromosome ◽

Intrinsic Property ◽

Transmission Ratio Distortion ◽

Chromosome 17 ◽

Transmission Ratio ◽

Quantitative Character ◽

Congenic Lines ◽

Ratio Distortion ◽

T Haplotype

ABSTRACT Transmission ratio distortion is a characteristic of complete t-haplotypes, such that heterozygous males preferentially transmit the t-haplotype bearing chromosome 17 to the majority of their progeny. At least two genes contained within the t-haplotype have been identified as being required for such high transmission ratios. In this study we examine the effects of the genetic background and the chromosome homologous to the t-haplotype on transmission ratio distortion. We use two different congenic lines: (1) BTBRTF/Nev.Ttf/t12, in which the t12 haplotype has a transmission ratio of 52%, and (2) C3H/DiSn.Ttf/t12, in which the t12 haplotype has a transmission ratio of 99%. By intercrossing these two strains to produce reciprocal F1 and F2 generations, we have isolated the effects of the homologous chromosome 17 from the effects of the genetic background. We demonstrate that both the homologous chromosome and the genetic background have profound effects on t-haplotype transmission ratio distortion. Furthermore, it is evident that the t-haplotype transmission ratio behaves as a quantitative character rather than an intrinsic property of t-haplotypes.

Download Full-text

The Putative Oncogene Pim-1 in the Mouse: Its Linkage and Variation Among t Haplotypes

Genetics ◽

10.1093/genetics/117.3.533 ◽

1987 ◽

Vol 117 (3) ◽

pp. 533-541

Author(s):

Joseph H Nadeau ◽

Sandra J Phillips

Keyword(s):

Restriction Fragment ◽

Inbred Mice ◽

Globin Gene ◽

Inbred Strains ◽

Chromosome 17 ◽

Wild Type ◽

Alpha Crystallin ◽

T Complex ◽

Variant Alleles ◽

Apparent Association

ABSTRACT Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudoalpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.

Download Full-text

A Chlamydomonas Homologue of the Putative Murine t Complex Distorter Tctex-2 Is an Outer Arm Dynein Light Chain

The Journal of Cell Biology ◽

10.1083/jcb.137.5.1081 ◽

1997 ◽

Vol 137 (5) ◽

pp. 1081-1090 ◽

Cited By ~ 48

Author(s):

Ramila S. Patel-King ◽

Sharon E. Benashski ◽

Alistair Harrison ◽

Stephen M. King

Keyword(s):

Molecular Analysis ◽

Light Chain ◽

Meiotic Drive ◽

Cytoplasmic Dynein ◽

Transmission Ratio Distortion ◽

Dynein Light Chain ◽

Wild Type ◽

Biochemical Model ◽

T Complex ◽

Ratio Distortion

Molecular analysis of a 19,000-Mr protein from the Chlamydomonas flagellum reveals that it is homologous to the t complex–encoded protein Tctex-2, which is a candidate for one of the distorter products that cause the extreme transmission ratio distortion (meiotic drive) of the murine t complex. The 19,000-Mr protein is extracted from the axoneme with 0.6 M NaCl and comigrates with the outer dynein arm in sucrose density gradients. This protein also is specifically missing in axonemes prepared from a mutant that does not assemble the outer arm. These data raise the possibility that Tctex-2 is a sperm flagellar dynein component. Combined with the recent identification of Tctex-1 (another distorter candidate) as a light chain of cytoplasmic dynein, these results lead to a biochemical model for how differential defects in spermiogenesis that result in the phenomenon of meiotic drive might be generated in wild-type vs t-bearing sperm.

Download Full-text

A structural gene (Tcp-1) within the mouse t complex is separable from effects on tail length and lethality but may be associated with effects on spermatogenesis

Genetics Research ◽

10.1017/s0016672300020474 ◽

1981 ◽

Vol 38 (2) ◽

pp. 115-123 ◽

Cited By ~ 22

Author(s):

Lee M. Silver

Keyword(s):

Genetic Basis ◽

Genetic Factors ◽

Tail Length ◽

Transmission Ratio Distortion ◽

Transmission Ratio ◽

Cell Protein ◽

Wild Type ◽

T Complex ◽

Interaction Factor ◽

Ratio Distortion

SUMMARYThe Tcp-1 gene is located within the t complex and codes for a major testicular cell protein called p63/6.9. All wild-type chromosomes carry the Tcp-1b allele which codes for a basic form of this protein, while all complete t haplotypes carry the Tcp-1a allele which codes for an acidic form of this protein. It is not clear whether the Tcp-1 gene is associated with phenotypic effects of t haplotypes on embryogenesis and/or spermatogenesis, since the genetic basis for these effects is extremely complex. The elegant analysis of Lyon & Mason (1977) has allowed the identification and separation of a family of genetic factors which interact to produce the observed phenotypes associated with various combinations of t haplotypes. The data summarized in this report indicate that the Tcp-1a locus is separable from all of the identified t haplotype factors except for one; a complete correlation has been obtained between Tcp-1a and a proximal t haplotype factor which is involved in effects on transmission ratio distortion. Two other novel points emerge from this analysis. First, it appears that the tail interaction factor and the proximal sperm factors represent distinct genetic loci. Second, the accumulated data lead to the proposal that the TOrl chromosome carries a short segment of t haplotype chromatin containing Tcp-1a and proximal sperm factors involved in transmission ratio distortion and sterility.

Download Full-text

Deletion of mouse t-complex distorter-1 produces an effect like that of the t-form of the distorter

Genetics Research ◽

10.1017/s0016672300030147 ◽

1992 ◽

Vol 59 (1) ◽

pp. 27-33 ◽

Cited By ~ 18

Author(s):

Mary F. Lyon

Keyword(s):

Male Sterility ◽

Differential Susceptibility ◽

Proximal Part ◽

Transmission Ratio Distortion ◽

Chromosome 17 ◽

Transmission Ratio ◽

T Complex ◽

Severe Impairment ◽

Ratio Distortion ◽

Distorter Gene

SummaryAn allele of the mouse brachyury locus, T22H, had been shown previously to involve a deletion of several markers in the proximal part of chromosome 17, and almost certainly includes deletion of the t-complex distorter gene Tcd-1. The effects of T22H on transmission ratio distortion and male sterility caused by the t-complex were compared with those of a partial t-haplotype th51, which carries the t-form of the distorter Tcd-1t. In combination with the complete haplotypetf32, T22H caused severe impairment of male fertility, but males of genotype T22H/t6 or T22H/thSl were normally fertile. These results were very similar to those obtained when th51 was in combination with the same haplotypes. In effect on transmission ratio T22H was again similar to thSI, in that it produced a marked increase in the transmission of the haplotype t6. To test whether the effects of T22H were due to deletion of elements other than Tcd-1, the effect of T22H on transmission of the partial haplotype th2 was compared with that of the deletion Thv. Again T22H markedly increased transmission of the t-haplotype and the effect was significantly greater than the small effect produced by Thp.It is concluded that deletion of the distorter Tcd-1 has an effect like that of the t-form of this distorter, Tcd-1t, and hence that Ted-11 must be an amorph or hypomorph. It is speculated that other t-complex distorters, Tcd-2t and Tcd-3t may also be amorphs or hypomorphs. Thus, the phenomena of transmission ratio distortion and male sterility due to the t-complex appear to be brought about by differential susceptibility of wild-type and t-responder alleles, Tcr+ and Tcrt, to a shortage of distorter gene product.

Download Full-text