Craniofacial shape transition across the house mouse hybrid zone: implications for the genetic architecture and evolution of between-species differences.
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ABSTRACT:
SUBMITTER: Pallares LF
PROVIDER: S-EPMC4896993 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prostate tumors arise primarily in the peripheral zone (PZ) of the prostate, but 20-30% arise in the transition zone (TZ). Zone of origin may have prognostic value or reflect distinct molecular subtypes; however, it can be difficult to determine in practice. Using whole-genome gene expression, we built a signature of zone using normal tissue from five individuals and found that it successfully classified nine tumors of known zone. Hypothesizing that this signature captures tumor zone of origin, we assessed its relationship with clinical factors among 369 tumors of unknown zone from radical prostatectomies (RPs) and found that tumors that molecularly resembled TZ tumors showed lower mortality (P = 0.09) that was explained by lower Gleason scores (P = 0.009). We further applied the signature to an earlier study of 88 RP and 333 transurethral resection of the prostate (TURP) tumor samples, also of unknown zone, with gene expression on ~6000 genes. We had observed previously substantial expression differences between RP and TURP specimens, and hypothesized that this might be because RPs capture primarily PZ tumors, whereas TURPs capture more TZ tumors. Our signature distinguished these two groups, with an area under the receiver operating characteristic curve of 87% (P < 0.0001). Our findings that zonal differences in normal tissue persist in tumor tissue and that these differences are associated with Gleason score and sample type suggest that subtypes potentially resulting from different etiologic pathways might arise in these zones. Zone of origin may be important to consider in prostate tumor biomarker research.
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Project description:Hybrid zones are unique biological interfaces that reveal both population level and species level evolutionary processes. A genome-scale approach to assess gene flow across hybrid zones is vital, and now possible. In Mexican towhees (genus Pipilo), several morphological hybrid gradients exist. We completed a genome survey across one such gradient (9 populations, 140 birds) using mitochondrial DNA, 28 isozyme, and 377 AFLP markers. To assess variation in introgression among loci, cline parameters (i.e., width, center) for the 61 clinally varying loci were estimated and compiled into genomic distributions for tests against three empirical models spanning the range of observed cline shape. No single model accounts for observed variation in cline shape among loci. Numerous backcross individuals near the gradient center confirm a hybrid origin for these populations, contrary to a previous hypothesis based on social mimicry and character displacement. In addition, the observed variation does not bin into well-defined categories of locus types (e.g., neutral vs. highly selected). Our multi-locus analysis reveals cross-genomic variation in selective constraints on gene flow and locus-specific flexibility in the permeability of the interspecies membrane.
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Project description:Resolving the mechanistic and genetic bases of reproductive barriers between species is essential to understanding the evolutionary forces that shape speciation. Intrinsic hybrid incompatibilities are often treated as fixed between species, yet there can be considerable variation in the strength of reproductive isolation between populations. The extent and causes of this variation remain poorly understood in most systems. We investigated the genetic basis of variable hybrid male sterility (HMS) between two recently diverged subspecies of house mice, Mus musculus domesticus and Mus musculus musculus We found that polymorphic HMS has a surprisingly complex genetic basis, with contributions from at least five autosomal loci segregating between two closely related wild-derived strains of M. m. musculus One of the HMS-linked regions on chromosome 4 also showed extensive introgression among inbred laboratory strains and transmission ratio distortion (TRD) in hybrid crosses. Using additional crosses and whole genome sequencing of sperm pools, we showed that TRD was limited to hybrid crosses and was not due to differences in sperm motility between M. m. musculus strains. Based on these results, we argue that TRD likely reflects additional incompatibilities that reduce hybrid embryonic viability. In some common inbred strains of mice, selection against deleterious interactions appears to have unexpectedly driven introgression at loci involved in epistatic hybrid incompatibilities. The highly variable genetic basis to F1 hybrid incompatibilities between closely related mouse lineages argues that a thorough dissection of reproductive isolation will require much more extensive sampling of natural variation than has been commonly utilized in mice and other model systems.
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Project description:Hybrids between species are often sterile or inviable. This form of reproductive isolation is thought to evolve via the accumulation of mutations that interact to reduce fitness when combined in hybrids. Mathematical formulations of this "Dobzhansky-Muller model" predict an accelerating buildup of hybrid incompatibilities with divergence time (the "snowball effect"). Although the Dobzhansky-Muller model is widely accepted, the snowball effect has only been tested in two species groups. We evaluated evidence for the snowball effect in the evolution of hybrid male sterility among subspecies of house mice, a recently diverged group that shows partial reproductive isolation. We compared the history of subspecies divergence with patterns of quantitative trait loci (QTL) detected in F2 intercrosses between two pairs of subspecies (Mus musculus domesticus with M. m. musculus and M. m. domesticus with M. m. castaneus). We used a recently developed phylogenetic comparative method to statistically measure the fit of these data to the snowball prediction. To apply this method, QTL were partitioned as either shared or unshared in the two crosses. A heuristic partitioning based on the overlap of QTL confidence intervals produced unambiguous support for the snowball effect. An alternative approach combining data among crosses favored the snowball effect for the autosomes, but a linear accumulation of incompatibilities for the X chromosome. Reasoning that the X chromosome analyses are complicated by low mapping resolution, we conclude that hybrid male sterility loci have snowballed in house mice. Our study illustrates the power of comparative genetic mapping for understanding mechanisms of speciation.
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Project description:Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone.
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Project description:Comparative genetic mapping provides insights into the evolution of the reproductive barriers that separate closely related species. This approach has been used to document the accumulation of reproductive incompatibilities over time, but has only been applied to a few taxa. House mice offer a powerful system to reconstruct the evolution of reproductive isolation between multiple subspecies pairs. However, studies of the primary reproductive barrier in house mice-hybrid male sterility-have been restricted to a single subspecies pair: Mus musculus musculus and Mus musculus domesticus. To provide a more complete characterization of reproductive isolation in house mice, we conducted an F(2) intercross between wild-derived inbred strains from Mus musculus castaneus and M. m. domesticus. We identified autosomal and X-linked QTL associated with a range of hybrid male sterility phenotypes, including testis weight, sperm density, and sperm morphology. The pseudoautosomal region (PAR) was strongly associated with hybrid sterility phenotypes when heterozygous. We compared QTL found in this cross with QTL identified in a previous F(2) intercross between M. m. musculus and M. m. domesticus and found three shared autosomal QTL. Most QTL were not shared, demonstrating that the genetic basis of hybrid male sterility largely differs between these closely related subspecies pairs. These results lay the groundwork for identifying genes responsible for the early stages of speciation in house mice.
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Project description:Host-parasite interaction studies across hybrid zones often focus on host genetic variation, treating parasites as homogeneous. 'Intimately' associated hosts and parasites might be expected to show similar patterns of genetic structure. In the literature, factors such as no intermediate host and no free-living stage have been proposed as 'intimacy' factors likely constraining parasites to closely follow the evolutionary history of their hosts. To test whether the whipworm, Trichuris muris, is intimately associated with its house mouse host, we studied its population genetics across the European house mouse hybrid zone (HMHZ) which has a strong central barrier to gene flow between mouse taxa. T. muris has a direct life cycle and nonmobile free stage: if these traits constrain the parasite to an intimate association with its host we expect a geographic break in the parasite genetic structure across the HMHZ. We genotyped 205 worms from 56 localities across the HMHZ and additionally T. muris collected from sympatric woodmice (Apodemus spp.) and allopatric murine species, using mt-COX1, ITS1-5.8S-ITS2 rDNA and 10 microsatellites. We show four haplogroups of mt-COX1 and three clear ITS1-5.8S-ITS2 clades in the HMHZ suggesting a complex demographic/phylogeographic history. Microsatellites show strong structure between groups of localities. However, no marker type shows a break across the HMHZ. Whipworms from Apodemus in the HMHZ cluster, and share mitochondrial haplotypes, with those from house mice. We conclude Trichuris should not be regarded as an 'intimate' parasite of the house mouse: while its life history might suggest intimacy, passage through alternate hosts is sufficiently common to erase signal of genetic structure associated with any particular host taxon.
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Project description:Prostate cancer arises in the transition zone (TZ) in approximately 20-25% of cases. Modern biopsy and surveillance protocols, and advances in prostate cancer imaging, have renewed interest in TZ prostate cancers. We compared TZ and PZ prostate cancer to determine if cancer location is independently associated with better outcomes.We evaluated an expanded cohort of 1354 men who underwent radical prostatectomy between 1983 and 2003 with updated long-term clinical follow-up. Regression models were used to compare the volume of high-grade (Gleason 4 or 5) cancer and total cancer volume by location. Uni- and multi-variable logistic regression models tested the associations between cancer location and adverse pathologic features. Multivariable proportional hazard models were fit to examine cancer recurrence.Patients with TZ cancer presented with higher pre-operative serum PSA values (11.07 vs. 7.86?ng/ml) and larger total cancer volume (7.1 vs. 3.8?cc). Patients with TZ cancer had decreased odds of seminal vesicle invasion (OR 0.08, 95% CI 0.03, 0.21), extra-capsular extension (OR 0.56, 95% CI 0.35, 0.92), and lymphovascular invasion (OR 0.48, 95% CI 0.27, 0.87) in multivariable models. TZ cancers were independently associated with decreased hazard of tumor recurrence (HR 0.62, 95% CI 0.43, 0.90).TZ cancer prostate is associated with favorable pathologic features and better recurrence-free survival despite being diagnosed with larger cancers and higher PSA values. Tumor location should be taken into account when stratifying patient risk before and after prostatectomy, particularly with the evolving role of imaging in prostate cancer management.
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Project description:Speciation occurs when populations diverge and become reproductively isolated from each other. Natural selection is commonly accepted to play a large role in this process, and it has been widely assumed that reproductive isolation often results as a by-product of divergence driven by adaptation in allopatry. When such populations come into secondary contact, reinforcement can act to strengthen reproductive isolation, but the frequency and importance of this process are still unknown. Here, we explored genomic signatures of selection in allopatry and sympatry for loci associated with reproductive isolation using a natural primate hybrid zone. By analysing reduced-representation sequencing data, we quantified admixture and population structure across a howler monkey hybrid zone and examined the relationship between locus-specific differentiation and introgression. We detected extensive admixture that was mostly limited to the narrow contact zone. Loci with reduced introgression into the heterospecific genomic background (the pattern expected for loci associated with reproductive isolation due to selection against hybrids) were significantly more differentiated between allopatric parental populations than loci with neutral and increased introgression, supporting the hypothesis that reproductive isolation is a by-product of divergence in allopatry. Further, loci with reduced introgression showed greater differentiation in sympatry than in allopatry, suggesting a role for reinforcement. Thus, our results reflect multiple forms of selection that have shaped reproductive isolation in this system. We conclude that reproductive isolation may have initially been driven by divergence in allopatry, but later reinforced by divergent selection in sympatry.
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Project description:BACKGROUND:Organismal fitness can be determined at early life-stages, but phenotypic variation at early life-stages is rarely considered in studies on evolutionary diversification. The trophic apparatus has been shown to contribute to sympatric resource-mediated divergence in several taxa. However, processes underlying diversification in trophic traits are poorly understood. Using phenotypically variable Icelandic Arctic charr (Salvelinus alpinus), we reared offspring from multiple families under standardized laboratory conditions and tested to what extent family (i.e. direct genetic and maternal effects) contributes to offspring morphology at hatching (H) and first feeding (FF). To understand the underlying mechanisms behind early life-stage variation in morphology, we examined how craniofacial shape varied according to family, offspring size, egg size and candidate gene expression. RESULTS:Craniofacial shape (i.e. the Meckel's cartilage and hyoid arch) was more variable between families than within families both across and within developmental stages. Differences in craniofacial morphology between developmental stages correlated with offspring size, whilst within developmental stages only shape at FF correlated with offspring size, as well as female mean egg size. Larger offspring and offspring from females with larger eggs consistently had a wider hyoid arch and contracted Meckel's cartilage in comparison to smaller offspring. CONCLUSIONS:This study provides evidence for family-level variation in early life-stage trophic morphology, indicating the potential for parental effects to facilitate resource polymorphism.
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