Recombination between the mouse Y chromosome short arm and an additional Y short arm-derived chromosomal segment attached distal to the X chromosome PAR

Abstract

In a male mouse, meiosis markers of processed DNA double strand breaks (DSBs) such as DMC1 and RAD51 are regularly seen in the non-PAR region of the X chromosome; these disappear late in prophase prior to entry into the first meiotic metaphase. Marker evidence for DSBs occurring in the non-PAR region of the Y chromosome is limited. Nevertheless, historically it has been documented that recombination can occur within the mouse Y short arm (Yp) when an additional Yp segment is attached distal to the X and/or the Y pseudoautosomal region (PAR). A number of recombinants identified among offsprings involved unequal exchanges involving repeated DNA segments; however, equal exchanges will have frequently been missed because of the paucity of markers to differentiate between the two Yp segments. Here, we discuss this historical data and present extensive additional data obtained for two mouse models with Yp additions to the X PAR. PCR genotyping enabled identification of a wider range of potential recombinants; the proportions of Yp exchanges identified among the recombinants were 9.7 and 22.4 %. The frequency of these exchanges suggests that the Yp segment attached to the X PAR is subject to the elevated level of recombinational DSBs that characterizes the PAR.

Keywords: Meiosis; Mouse; Recombination; Short arm (Yp); Spo11; Y-chromosome.

Fig. 1

Origin of Sxr variants. (a) Wild type XY. (b) Duplication and translocation of Yp created Sxr ^a. (c) PAR-PAR recombination in XYSxr ^a males generates the XSxr ^a chromosome. (d) An unequal crossover in an XSxr ^aYSxr ^a male created the Sxr ^b deletion variant. (Color codes: Red = PAR; Blue = non-PAR X; Dark green = non-PAR Y except Sxr ^b; Light green = Sxr ^b; Yellow = Zfy1; Orange = Zfy2; Orange/Yellow = Zfy2/1 fusion gene.) ^* Rbmy copy number estimates based on information provided by Soh et al. (2014) and Mahadevaiah et al. (1998)

Fig. 2

Recombination in XSxr ^bY males. (a) PAR-PAR recombination. (b) Yp-Sxr ^b recombination with expanded views showing the Y gene content of the paired segments and of the two types of recombinant from crossover 1 (black cross); (c) Bar chart of non-recombinant (No) and recombinant (Yp-Sxr ^b, PAR-PAR) frequencies

Fig. 3

Recombination in XSxr ^bY* males. (a) The sex chromosomes of XSxr ^bY* males showing the complex Y*PAR and associated X-derived centromere, note that the original Y centromere is inactive. (b) PAR-PAR recombination arising from parasynapsed and staggered associations—note that the dicentric X and YSxr ^b (with inactive Y centromere) recombinant chromosomes are prone to loss at MI thus generating “O” gametes and are not present in the offspring. (c) Yp-Sxr ^b recombination with expanded views showing the Y gene content of the paired segments and potential crossovers—no recombinants were obtained from crossover 2, and recombinants from crossover 4 could not be detected due to a lack of markers. (d) The four types of recombinant from crossovers 1 and 3. (e) Bar chart of non-recombinant and recombinant frequencies. “Other n = 4” comprises one animal from an XΔSxr ^b gamete and three from Y*^ΔΔSxra gametes (generated by crossover 3)

Fig. 4

X-Y bivalent configurations at pachytene in XSxr ^bY and XSxr ^bY* males. Each panel has a diagram of the predicted crossover event, a low magnification view showing the X-Y bivalent in a γH2AX-stained (red) sex chromatin cloud together with near-by autosomes, a higher power view of the X-Y bivalent with the γH2AX staining removed, and a drawing of the deduced X-Y bivalent configuration highlighting the centromere positions. Note that the red CREST staining of active centromeres often appears as yellow where it overlaps the green chromosome axis. (a) XSxr ^bY with Yp-Sxr ^b synapsis. (b) XSxr ^bY with PAR-PAR synapsis. (c) XSxr ^bY* with centromere-centromere association—this is likely to be due to synapsis driven by homology of Sstx sequences adjacent to the X and Y*(X-derived) centromeres. (d) XSxr ^bY* with Yp-Sxr ^b synapsis. (e) XSxr ^bY* with centromere-centromere and Yp-Sxr ^b synapsis. (f) XSxr ^bY* with PAR-PAR synapsis—parasynapsis and staggered synapsis cannot be differentiated at this resolution. The staggered configuration is indicated in the black square