The effect of multiple simple Robertsonian heterozygosity on chromosome pairing and fertility of wild-stock house mice <i>(Mus musculus domesticus)</i>

Abstract

The influence of Robertsonian (Rb) heterozygosity on fertility has been the subject of much study in the house mouse. However, these studies have been largely directed at single simple heterozygotes (heterozygous for a single Rb metacentric) or complex heterozygotes (heterozygous for several to many metacentrics which share common chromosome arms). In this paper we describe studies on male multiple simple heterozygotes, specifically the F₁ products of crosses between wild-stock mice homozygous for four or seven metacentrics and wild-stock mice with a standard all-acrocentric karyotype; these F₁ products were characterized by four and seven trivalents at meiosis I, respectively. Mice with the same karyotype, but two different genetic backgrounds were examined. Although a range of meiotic and fertility studies were conducted, particular emphasis was paid to analysis of chromosome pairing, previously not well-described in multiple simple heterozygous mice. The progression of spermatocytes through prophase I was followed by electron microscopy of surface spread material. As previously shown for single simple Rb heterozygotes, the trivalents that characterize multiple simple heterozygotes initially showed delayed pairing of the centromeric region and later showed side arm formation, resulting from non-homologous pairing by the centromeric ends of the acrocentric chromosomes. In the four trivalent groups of mice, 15 and 32% of trivalents showed unpairing in the centromeric region at mid pachytene; equivalent values were 29 and 39% for the seven trivalent groups. Pairing abnormalities (largely attachments and interlocks between trivalents and between a trivalent and the XY configuration) were observed in 18 and 23% of mid pachytene cells in the four trivalent groups and 36 and 49% of cells in the seven trivalent groups. The greater level of pachytene irregularity (unpairing and pairing abnormalities) in seven versus four trivalent heterozygotes was mirrored in terms of higher anaphase I nondisjunction frequency and lower germ cell counts. However, while pachytene irregularities appear to contribute to germ cell death, examples of male sterility in our material undoubtedly also involve genic incompatibilities.

Origin of the chromosomal radiation of Madeiran house mice: a microsatellite analysis of metacentric chromosomes

“…It has been demonstrated that house mice heterozygous for metacentrics have impaired reproductive fitness (for example, Wallace et al, 1992Wallace et al, , 2002Saïd et al, 1993;Hauffe and Searle, 1998), and that there are recombination effects in the vicinity of the centromere in such heterozygotes (for example, Davisson and Akeson, 1993;Bidau et al, 2001;Merico et al, 2003). Thus, one or both of these processes could affect gene flow in the centromeric region of the metacentric chromosomes investigated by us.…”

Independent fusions and recent origins of sex chromosomes in the evolution and diversification of glass knife fishes (Eigenmannia)

“…The fact that one of the chromosomes homologous to the Y chromosome is fused to two different chromosomes in this species pair may have interesting evolutionary implications (Figure 5b). This is likely to result in a significant level of infertility in potential F 1 hybrids because of abnormal meiotic segregation (Wallace et al, 2002). This effect would likely be compounded if the chromosome happened to harbor sex-determining genes, given the disproportionate importance of sex chromosomes in the evolution of post-mating isolation mechanisms (Presgraves, 2008;Kitano et al, 2009).…”

Fertility assessment in hybrids between monobrachially homologous Rb races of the house mouse from the island of Madeira: implications for modes of chromosomal evolution

“…Heterozygous disadvantage for chromosomal rearrangements results from the incorrect segregation of chromosomes during meiosis, leading to the formation of fertile aneuploid gametes and embryonic mortality (King, 1993;Marchetti et al, 1999). Premeiotic perturbations have been also observed in some cases causing a reduction in germ cell number (Garagna et al, 1990;Hauffe and Searle, 1998;Banaszek et al, 2000;Wallace et al, 2002). Data from different mammalian species (including human) have shown that values of underdominance vary according to the nature of the rearrangement, the chromosomes concerned, the breakpoint site, the gender and also the genetic context and age (King, 1993;Searle, 1993;Djelati et al, 1997;Hauffe and Searle, 1998;Castiglia and Capanna, 2000;Wallace et al, 2002;Pellestor et al, 2005;Anton et al, 2006).…”

“…Heterozygotes for fusions produce trivalents at meiosis, formed by the pairing of each metacentric and its two acrocentric homologs. These meiotic configurations usually result in very low nondisjunction (NDJ) rates when few in number, but the degree of gametogenetic impairment increases when many are present (Garagna et al, 1990;Hauffe and Searle, 1998;Castiglia and Capanna, 2000;Wallace et al, 2002). In some instances, however, parapatric Rb races carry monobrachially homologous fusions; that is, Rb metacentrics that have one chromosome arm in common.…”

“…These data were measured in laboratory-bred heterozygotes carrying wild Rb metacentrics introgressed into house mouse strains. As the interaction between the strain and wild genomes is known to affect fertility scores, the reproductive fitness of such heterozygotes needs to be reassessed in wild genomes (Wallace et al, 2002). However, natural situations in which hybrids between related races carry a single chain of four chromosomes are scarce (Piálek et al, 2005).…”