Priscilla K. Tucker

Subspecific origin and haplotype diversity in the laboratory mouse

Here we provide a genome-wide, high-resolution map of the phylogenetic origin of the genome of most extant laboratory mouse inbred strains. Our analysis is based on the genotypes of wild-caught mice from three subspecies of Mus musculus. We show that classical laboratory strains are derived from a few fancy mice with limited haplotype diversity. Their genomes are overwhelmingly Mus musculus domesticus in origin, and the remainder is mostly of Japanese origin. We generated genome-wide haplotype maps based on identity by descent from fancy mice and show that classical inbred strains have limited and non-randomly distributed genetic diversity. In contrast, wild-derived laboratory strains represent a broad sampling of diversity within M. musculus. Intersubspecific introgression is pervasive in these strains, and contamination by laboratory stocks has played a role in this process. The subspecific origin, haplotype diversity and identity by descent maps can be visualized using the Mouse Phylogeny Viewer (see URLs).

Abrupt cline for sex chromosomes in a hybrid zone between two species of mice.

We compared the patterns of movement of sex chromosomal and autosomal loci along a 160 km transect across a zone of hybridization between M. domesticus and M. musculus in southern Germany and western Austria using seven genetic markers. These included one Y‐specific DNA sequence (YB10), two X‐specific loci (DXWas68 and DXWas31), and four autosomal isozyme loci (Es‐10, Es‐1, Mpi‐1, and Np‐1). Random effects logistic regression analysis enabled us to examine the relationship between M. domesticus allele frequency and geographic distance from the western edge of the hybrid zone and allowed statistical evaluation of differences in cline midpoint and width among loci. More limited movement was observed for all three sex chromosomal markers across the zone compared with three of the four autosomal markers. If differential movement reflects fitness differences of specific alleles (or alleles at closely linked loci) on a hybrid background, then alleles that move to a limited extent across a hybrid zone may contribute to hybrid breakdown between two species. The limited flow of both X‐ and Y‐specific alleles suggest that sex chromosomes have played an important role in Mus speciation.

THE VARIABLE GENOMIC ARCHITECTURE OF ISOLATION BETWEEN HYBRIDIZING SPECIES OF HOUSE MICE

Studies of the genetics of hybrid zones can provide insight into the genomic architecture of species boundaries. By examining patterns of introgression of multiple loci across a hybrid zone, it may be possible to identify regions of the genome that have experienced selection. Here, we present a comparison of introgression in two replicate transects through the house mouse hybrid zone through central Europe, using data from 41 single nucleotide markers. Using both genomic and geographic clines, we found many differences in patterns of introgression between the two transects, as well as some similarities. We found that many loci may have experienced the effects of selection at linked sites, including selection against hybrid genotypes, as well as positive selection in the form of genotypes introgressed into a foreign genetic background. We also found many positive associations of conspecific alleles among unlinked markers, which could be caused by epistatic interactions. Different patterns of introgression in the two transects highlight the challenge of using hybrid zones to identify genes underlying isolation and raise the possibility that the genetic basis of isolation between these species may be dependent on the local population genetic make‐up or the local ecological setting.

Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states

Familial Mediterranean fever (FMF; MIM 249100) is an autosomal recessive disease characterized by recurrent attacks of fever with synovial, pleural or peritoneal inflammation. The disease is caused by mutations in the gene encoding the pyrin protein. Human population studies have revealed extremely high allele frequencies for several different pyrin mutations, leading to the conclusion that the mutant alleles confer a selective advantage. Here we examine the ret finger protein (rfp) domain (which contains most of the disease-causing mutations) of pyrin during primate evolution. Amino acids that cause human disease are often present as wild type in other species. This is true at positions 653 (a novel mutation), 680, 681, 726, 744 and 761. For several of these human mutations, the mutant represents the reappearance of an ancestral amino acid state. Examination of lineage-specific dN/dS ratios revealed a pattern consistent with the signature of episodic positive selection. Our data, together with previous human population studies, indicate that selective pressures may have caused functional evolution of pyrin in humans and other primates.

Male mating behaviour and patterns of sperm precedence in Arctic ground squirrels

Ground squirrels (genus Spermophilus) display considerable interspecific variation in male reproductive behaviour. Although male Arctic ground squirrels, S. parryii plesius, are territorial during the mating period, males in several other species ofSpermophilusare not. To begin exploring the reasons for this behavioural diVerence, patterns of mating behaviour and sperm precedence were characterized for a free-living population of S. parryii plesius. Twenty females that were monitored continuously throughout behavioural oestrus consorted and presumably copulated with a mean of 1.9&0.8 males during a single period of sexual receptivity. A combination of electrophoretic and DNA fingerprinting analyses revealed that more than 90% of pups in litters (N=11) reared by females that consorted with two or more males were sired by a females first mate. The percentage of young sired by each of a females consorts did not vary with either consortship duration or the interval between consortships by diVerent males. Instead, the only consistent correlate of paternity was consortship order. Both pre-consortship calling and post-consortship defence of females were significantly associated with first consortships, suggesting that males were able to distinguish unmated females from females that had already copulated. Because the probability of siring young should influence which females are preferred as mates and how males compete for access to those females, comparative studies of sperm precedence patterns may yield insights into the evolution of interspecific variation in male mating behaviour. ? 1997 The Association for the Study of Animal Behaviour

Genome-wide architecture of reproductive isolation in a naturally occurring hybrid zone between Mus musculus musculus and M. m. domesticus

Studies of a hybrid zone between two house mouse subspecies (Mus musculus musculus and M. m. domesticus) along with studies using laboratory crosses reveal a large role for the X chromosome and multiple autosomal regions in reproductive isolation as a consequence of disrupted epistasis in hybrids. One limitation of previous work has been that most of the identified genomic regions have been large. The goal here is to detect and characterize precise genomic regions underlying reproductive isolation. We surveyed 1401 markers evenly spaced across the genome in 679 mice collected from two different transects. Comparisons between transects provide a means for identifying common patterns that likely reflect intrinsic incompatibilities. We used a genomic cline approach to identify patterns that correspond to epistasis. From both transects, we identified contiguous regions on the X chromosome in which markers were inferred to be involved in epistatic interactions. We then searched for autosomal regions showing the same patterns and found they constitute about 5% of autosomal markers. We discovered substantial overlap between these candidate regions underlying reproductive isolation and QTL for hybrid sterility identified in laboratory crosses. Analysis of gene content in these regions suggests a key role for several mechanisms, including the regulation of transcription, sexual conflict and sexual selection operating at both the postmating prezygotic and postzygotic stages of reproductive isolation. Taken together, these results indicate that speciation in two recently diverged (c. 0.5 Ma) house mouse subspecies is complex, involving many genes dispersed throughout the genome and associated with distinct functions.

Geographic origin of the Y Chromosomes in "old" inbred strains of mice

Six distinct Y Chromosomes (Chr) were identified among 39 standard inbred strains of mice with five probes that identified Y Chr-specific restriction fragments on Southern blots. Three Y Chr types, distributed among 31 strains, were of Asian Mus musculus origin. The remaining three Y Chr types, distributed among eight strains, were of M. domesticus origin. The Asian source of the M. musculus Y Chr was confirmed by determining the DNA sequence of 221 bp from an open reading frame within the Sry (sex determining region Y) gene (Gubbay et al., Nature 346 245–250, 1990) in three inbred strains (C57BL/6J, AKR/J, and SWR/J) and comparing the sequence to the homologous sequences derived from wild caught European and Asian M. musculus males. These data indicate that a minimum of six male mice contributed to the formation of the old inbred strains.

Reinforcement selection acting on the European house mouse hybrid zone

Behavioural isolation may lead to complete speciation when partial postzygotic isolation acts in the presence of divergent‐specific mate‐recognition systems. These conditions exist where Mus musculus musculus and M. m. domesticus come into contact and hybridize. We studied two mate‐recognition signal systems, based on urinary and salivary proteins, across a Central European portion of the mouse hybrid zone. Introgression of the genomic regions responsible for these signals: the major urinary proteins (MUPs) and androgen binding proteins (ABPs), respectively, was compared to introgression at loci assumed to be nearly neutral and those under selection against hybridization. The preference of individuals taken from across the zone regarding these signals was measured in Y mazes, and we develop a model for the analysis of the transition of such traits under reinforcement selection. The strongest assortative preferences were found in males for urine and females for ABP. Clinal analyses confirm nearly neutral introgression of an Abp locus and two loci closely linked to the Abp gene cluster, whereas two markers flanking the Mup gene region reveal unexpected introgression. Geographic change in the preference traits matches our reinforcement selection model significantly better than standard cline models. Our study confirms that behavioural barriers are important components of reproductive isolation between the house mouse subspecies.

Tests for Positive Selection on Immune and Reproductive Genes in Closely Related Species of the Murine Genus Mus

We examine variation among species of Mus in four genes involved in reproduction and the immune response for evidence of positive selection: the sperm recognition gene Zp-3, the testis-determining locus Sry, the testicular cell surface matrix protein Tcp-1, and the immune system protein β2m. We use likelihood ratio tests in the context of a well-supported phylogeny to determine whether models that allow for positively selected sites fit the sequences better than models that assume purifying selection. We then apply a Bayesian approach to identify particular sites in each gene that have a high posterior probability of being under positive selection. We find no evidence of positive selection on the Tcp-1 gene, but for Zp-3, Sry, and β2m, models that allow for positively selected sites fit the sequences better than alternatives. For each of these genes, we identify sites that have a high (> 95%) posterior probability of being positively selected. For Zp-3, two of these sites occur near the sperm-binding region, while one occurs in a region whose functional role remains unstudied but where the pattern of change predicts functional importance. A single site in Sry shows an elevated rate of replacement substitution but occurs in a region of apparently little functional importance; therefore, relaxation of functional constraints may better explain the rapid evolution of this site. Three sites in β2m have a posterior probability > 50% of being under positive selection. While the functional role for two of these sites is unknown, the third is known to influence the ability of MHC class I molecules to present antigens to the immune system; therefore, the elevated rate of replacement substitutions at this site is consistent with selection acting to promote variability in immune system proteins.

Sperm-related phenotypes implicated in both maintenance and breakdown of a natural species barrier in the house mouse

The house mouse hybrid zone (HMHZ) is a species barrier thought to be maintained by a balance between dispersal and natural selection against hybrids. While the HMHZ is characterized by frequency discontinuities for some sex chromosome markers, there is an unexpected large-scale regional introgression of a Y chromosome across the barrier, in defiance of Haldanes rule. Recent work suggests that a major force maintaining the species barrier acts through sperm traits. Here, we test whether the Y chromosome penetration of the species barrier acts through sperm traits by assessing sperm characteristics of wild-caught males directly in a field laboratory set up in a Y introgression region of the HMHZ, later calculating the hybrid index of each male using 1401 diagnostic single nucleotide polymorphisms (SNPs). We found that both sperm count (SC) and sperm velocity were significantly reduced across the natural spectrum of hybrids. However, SC was more than rescued in the presence of the invading Y. Our results imply an asymmetric advantage for Y chromosome introgression consistent with the observed large-scale introgression. We suggest that selection on sperm-related traits probably explains a large component of patterns observed in the natural hybrid zone, including the Y chromosome penetration.