Investigating latitudinal clines for life history and stress resistance traits in Drosophila simulans from eastern Australia

Latitudinal clines have been demonstrated for many quantitative traits in Drosophila and are assumed to be due to climatic selection. However, clinal studies are often performed in species of Drosophila that contain common cosmopolitan inversion polymorphisms that also show clinal patterns. These inversion polymorphisms may be responsible for much of the observed clinal variation. Here, we consider latitudinal clines for quantitative traits in Drosophila simulans from eastern Australia. Drosophila simulans does not contain cosmopolitan inversion polymorphisms, so allows the study of clinal selection on quantitative traits that are not confounded by associations with inversions. Body size showed a strong linear cline for both females and males. Starvation resistance exhibited a weak linear cline in females, whereas chill-coma recovery exhibited a significant nonlinear cline in females only. No clinal pattern was evident for development time, male chill-coma recovery, desiccation or heat resistance. We discuss these results with reference to the role inversion polymorphisms play in generating clines in quantitative traits of Drosophila.     

A polymorphism within the equine CRISP3 gene is associated with stallion fertility in Hanoverian warmblood horses

Fertility of stallions is of high economic importance, especially for large breeding organisations and studs. Breeding schemes with respect to fertility traits and selection of stallions at an early stage may be improved by including molecular genetic markers associated with traits. The genes coding for equine cysteine-rich secretory proteins (CRISPs) are promising candidate genes because previous studies have shown that CRISPs play a role in the fertilising ability of male animals. We have previously characterised the three equine CRISP genes and identified a non-synonymous polymorphism in the CRISP1 gene. In this study, we report one non-synonymous polymorphism in the CRISP2 gene and four non-synonymous polymorphisms in the CRISP3 gene. All six CRISP polymorphisms were genotyped in 107 Hanoverian breeding stallions. Insemination records of stallions were used to analyse the association between CRISP polymorphisms and fertility traits. Three statistical models were used to evaluate the influence of single mutations, genotypes and haplotypes of the polymorphisms. The CRISP3 AJ459965:c.+622G>A SNP leading to the amino acid substitution E208K was significantly associated with the fertility of stallions. Stallions heterozygous for the CRISP3 c.+622G>A SNP had lower fertility than homozygous stallions (P = 0.0234). The pregnancy rate per cycle in these stallions was estimated to be approximately 7% lower than in stallions homozygous at this position.     

A Widespread Chromosomal Inversion Polymorphism Contributes to a Major Life-History Transition,Local Adaptation,and Reproductive Isolation

The role of chromosomal inversions in adaptation and speciation is controversial. Historically, inversions were thought to contribute to these processes either by directly causing hybrid sterility or by facilitating the maintenance of co-adapted gene complexes. Because inversions suppress recombination when heterozygous, a recently proposed local adaptation mechanism predicts that they will spread if they capture alleles at multiple loci involved in divergent adaptation to contrasting environments. Many empirical studies have found inversion polymorphisms linked to putatively adaptive phenotypes or distributed along environmental clines. However, direct involvement of an inversion in local adaptation and consequent ecological reproductive isolation has not to our knowledge been demonstrated in nature. In this study, we discovered that a chromosomal inversion polymorphism is geographically widespread, and we test the extent to which it contributes to adaptation and reproductive isolation under natural field conditions. Replicated crosses between the prezygotically reproductively isolated annual and perennial ecotypes of the yellow monkeyflower, Mimulus guttatus, revealed that alternative chromosomal inversion arrangements are associated with life-history divergence over thousands of kilometers across North America. The inversion polymorphism affected adaptive flowering time divergence and other morphological traits in all replicated crosses between four pairs of annual and perennial populations. To determine if the inversion contributes to adaptation and reproductive isolation in natural populations, we conducted a novel reciprocal transplant experiment involving outbred lines, where alternative arrangements of the inversion were reciprocally introgressed into the genetic backgrounds of each ecotype. Our results demonstrate for the first time in nature the contribution of an inversion to adaptation, an annual/perennial life-history shift, and multiple reproductive isolating barriers. These results are consistent with the local adaptation mechanism being responsible for the distribution of the two inversion arrangements across the geographic range of M. guttatus and that locally adaptive inversion effects contribute directly to reproductive isolation. Such a mechanism may be partially responsible for the observation that closely related species often differ by multiple chromosomal rearrangements.     

Epistasis in a quantitative trait captured by a molecular model of transcription factor interactions

With technological advances in genetic mapping studies more of the genes and polymorphisms that underlie Quantitative Trait Loci (QTL) are now being identified. As the identities of these genes become known there is a growing need for an analysis framework that incorporates the molecular interactions affected by natural polymorphisms. As a step towards such a framework we present a molecular model of genetic variation in sporulation efficiency between natural isolates of the yeast, Saccharomyces cerevisiae. The model is based on the structure of the regulatory pathway that controls sporulation. The model captures the phenotypic variation between strains carrying different combinations of alleles at known QTL. Compared to a standard linear model the molecular model requires fewer free parameters, and has the advantage of generating quantitative hypotheses about the affinity of specific molecular interactions in different genetic backgrounds. Our analyses provide a concrete example of how the thermodynamic properties of protein-protein and protein-DNA interactions naturally give rise to epistasis, the non-linear relationship between genotype and phenotype. As more causative genes and polymorphisms underlying QTL are identified, thermodynamic analyses of quantitative traits may provide a useful framework for unraveling the complex relationship between genotype and phenotype.     

Poor genetic differentiation but clear cytoform divergence among cryptic species in Simulium damnosum complex (Diptera: Simuliidae)

A complex cryptic species taxonomy has been developed for the flies that vector Onchocerca volvulus L euckart in A frica. This taxonomy names cytoforms of Simulium damnosum T heobald s.l. based on chromosomal inversion polymorphisms. Researchers have linked variation in cytoforms to variation in geographical distributions and biological traits, but have failed to demonstrate that many of these cytoforms are differentiated genetically or morphologically. This may be explained by recent divergence and incomplete lineage sorting of ancestral polymorphisms. Alternatively, it may be the outcome of ongoing gene flow, with inversions maintaining sets of co‐adapted alleles and selection driving inversion frequency differences across habitats. Here, our goals were to test species delimitations in the S. damnosum complex, and determine if the poor differentiation between these species is better explained by the ancestral polymorphisms or gene‐flow hypotheses. Geometric morphometric analysis and more intensive genetic sampling of populations in N igeria only reinforced the lack of clear divergence among S. damnosum complex cytoforms. By contrast, the first statistical estimates of evolutionary relationships based on chromosomal inversion polymorphism data revealed clear signs of divergence, which lends support to the ancestral polymorphisms hypothesis. But the latter analyses may be biased by non‐neutral evolution of inversion polymorphisms; more rigorous tests of cytoform‐based species hypothesis will require deeper sampling across populations and neutral genetic markers along with explicit modelling of genetic isolation and migration.     

The effect of developmental temperature on the genetic architecture underlying size and thermal clines in Drosophila melanogaster and D. simulans from the east coast of Australia

Body size and thermal tolerance clines in Drosophila melanogaster occur along the east coast of Australia. However the extent to which temperature affects the genetic architecture underlying the observed clinal divergence remains unknown. Clinal variation in these traits is associated with cosmopolitan chromosome inversions that cline in D. melanogaster. Whether this association influences the genetic architecture for these traits in D. melanogaster is unclear. Drosophila simulans shows linear clines in body size, but nonlinear clines in cold resistance. Clinally varying inversions are absent in D. simulans. Line-cross and clinal analyses were performed between tropical and temperate populations of D. melanogaster and D. simulans from the east coast of Australia to investigate whether clinal patterns and genetic effects contributing to clinal divergence in wing centroid size, thorax length, wing-to-thorax ratio, cold and heat resistance differed under different developmental temperatures (18 °C, 25 °C, and 29 °C). Developmental temperature influenced the genetic architecture in both species. Similarities between D. melanogaster and D. simulans suggest clinally varying inversion polymorphisms have little influence on the genetic architecture underlying clinal divergence in size in D. melanogaster. Differing genetic architectures across different temperatures highlight the need to consider different environments in future evolutionary and molecular studies of phenotypic divergence.     

Rapid parallel evolution of standing variation in a single,complex, genomic region is associated with life history in steelhead/rainbow trout

Rapid adaptation to novel environments may drive changes in genomic regions through natural selection. Such changes may be population-specific or, alternatively, may involve parallel evolution of the same genomic region in multiple populations, if that region contains genes or co-adapted gene complexes affecting the selected trait(s). Both quantitative and population genetic approaches have identified associations between specific genomic regions and the anadromous (steelhead) and resident (rainbow trout) life-history strategies of Oncorhynchus mykiss. Here, we use genotype data from 95 single nucleotide polymorphisms and show that the distribution of variation in a large region of one chromosome, Omy5, is strongly associated with life-history differentiation in multiple above-barrier populations of rainbow trout and their anadromous steelhead ancestors. The associated loci are in strong linkage disequilibrium, suggesting the presence of a chromosomal inversion or other rearrangement limiting recombination. These results provide the first evidence of a common genomic basis for life-history variation in O. mykiss in a geographically diverse set of populations and extend our knowledge of the heritable basis of rapid adaptation of complex traits in novel habitats.     

Climatic selection on genes and traits after a 100 year-old invasion: a critical look at the temperate-tropical clines in Drosophila melanogaster from eastern Australia

Drosophila melanogaster invaded Australia around 100 years ago, most likely through a northern invasion. The wide range of climatic conditions in eastern Australia across which D. melanogaster is now found provides an opportunity for researchers to identify traits and genes that are associated with climatic adaptation. Allozyme studies indicate clinal patterns for at least four loci including a strong linear cline in Adh and a non-linear cline in alpha-Gpdh. Inversion clines were initially established from cytological studies but have now been validated with larger sample sizes using molecular markers for breakpoints. Recent collections indicate that some genetic markers (Adh and In(3R)Payne) have changed over the last 20 years reflecting continuing evolution. Heritable clines have been established for quantitative traits including wing length/area, thorax length and cold and heat resistance. A cline in egg size independent of body size and a weak cline in competitive ability have also been established. Postulated clinal patterns for resistance to desiccation and starvation have not been supported by extensive sampling. Experiments under laboratory and semi-natural conditions have suggested selective factors generating clinal patterns, particularly for reproductive patterns over winter. Attempts are being made to link clinal variation in traits to specific genes using QTL analysis and the candidate locus approach, and to identify the genetic architecture of trait variation along the cline. This is proving difficult because of inversion polymorphisms that generate disequilibrium among genes. Substantial gaps still remain in linking clines to field selection and understanding the genetic and physiological basis of the adaptive shifts. However D. melanogaster populations in eastern Australia remain an excellent resource for understanding past and future evolutionary responses to climate change.     

The genetic architecture of quantitative traits: lessons from Drosophila

Understanding the genetic architecture of quantitative traits begins with identifying the genes regulating these traits, mapping the subset of genetically varying quantitative trait loci (QTLs) in natural populations, and pinpointing the molecular polymorphisms defining QTL alleles. Studies in Drosophila have revealed large numbers of pleiotropic genes that interact epistatically to regulate quantitative traits, and large numbers of QTLs with sex-, environment- and genotype-specific effects. Multiple molecular polymorphisms in regulatory regions of candidate genes are often associated with variation for complex traits. These observations offer valuable lessons for understanding the genetic basis of variation for complex traits in other organisms, including humans.     

Complex patterns of local adaptation in heat tolerance in Drosophila simulans from eastern Australia

Latitudinal clines are considered a powerful means of investigating evolutionary responses to climatic selection in nature. However, most clinal studies of climatic adaptation in Drosophila have involved species that contain cosmopolitan inversion polymorphisms that show clinal patterns themselves, making it difficult to determine whether the traits or inversions are under selection. Further, although climatic selection is unlikely to act on only one life stage in metamorphic organisms, a few studies have examined clinal patterns across life stages. Finally, clinal patterns of heat tolerance may also depend on the assay used. To unravel these potentially confounding effects on clinal patterns of thermal tolerance, we examined adult and larval heat tolerance traits in populations of Drosophila simulans from eastern Australia using static and dynamic (ramping 0.06 °C min^?1) assays. We also used microsatellites markers to clarify whether demographic factors or selection are responsible for population differentiation along clines. Significant cubic clinal patterns were observed for adult static basal, hardened and dynamic heat knockdown time and static basal heat survival in larvae. In contrast, static, hardened larval heat survival increased linearly with latitude whereas no clinal association was found for larval ramping survival. Significant associations between adult and larval traits and climatic variables, and low population differentiation at microsatellite loci, suggest a role for climatic selection, rather than demographic processes, in generating these clinal patterns. Our results suggest that adaptation to thermal stress may be species and life‐stage specific, complicating our efforts to understand the evolutionary responses to selection for increasing thermotolerance.     

Comparison between Pyrococcus horikoshii and Pyrococcus abyssi genome sequences reveals linkage of restriction-modification genes with large genome polymorphisms

Recent work suggests that restriction-modification gene complexes are mobile genetic elements that insert themselves into the genome and cause various genome rearrangements. In the present work, the complete genome sequences of Pyrococcus horikoshii and Pyrococcus abyssi, two species in a genus of hyperthermophilic archaeon (archaebacterium), were compared to detect large genome polymorphisms linked with restriction-modification gene homologs. Sequence alignments, GC content analysis, and codon usage analysis demonstrated the diversity of these homologs and revealed a possible case of relatively recent acquisition (horizontal transfer). In two cases out of the six large polymorphisms identified, there was insertion of a DNA segment with a modification gene homolog, accompanied by target deletion (simple substitution). In two other cases, homologous DNA segments carrying a modification gene homolog were present at different locations in the two genomes (transposition). In both cases, substitution (insertion/deletion) in one of the two loci was accompanied by inversion of adjacent chromosomal segment. In the fifth case, substitution by a DNA segment carrying type I restriction, modification, and specificity gene homologs was likewise accompanied by adjacent inversion. In the last case, two homologous DNA segments, were found at different loci in the two genomes (transposition), but only one of them had insertion of a modification homolog and an unknown ORF. The possible relationship of these polymorphisms to attack by restriction enzymes on the chromosome will be discussed.     

The gene encoding interleukin-13: a susceptibility locus for asthma and related traits

Asthma is a complex inflammatory disorder controlled by both genetic and environmental influences. Multiple genetic analyses have identified the T helper type 2 (Th2) cytokine gene cluster on chromosome 5q as a susceptibility locus for asthma. Recently, the Th2 cytokine interleukin-13 has been shown to be a critical mediator of the asthma phenotype in murine models. In this commentary we discuss several recent studies that have identified polymorphisms in the gene encoding interleukin-13. The consistent genetic associations of interleukin-13 with asthma and related traits across diverse ethnic populations in these studies provides strong support for the candidacy of this cytokine as a susceptibility locus for asthma and atopy on chromosome 5q31.     

Polymorphisms on SSC15q21-q26 Containing QTL for reproduction in Swine and its association with litter size

Several quantitative trait loci (QTL) for important reproductive traits (ovulation rate) have been identified on the porcine chromosome 15 (SSC15). To assist in the selection of positional candidate swine genes for these QTL on SSC15, twenty-one genes had already been assigned to SSC15 in a previous study in our lab, by using the radiation hybrid panel IMpRH. Further polymorphism studies were carried out on these positional candidate genes with four breeds of pigs (Duroc, Erhualian, Dahuabai and Landrace) harboring significant differences in reproduction traits. A total of nineteen polymorphisms were found in 21 genes. Among these, seven in six genes were used for association studies, whereby NRP2 polymorphism was found to be significantly (p < 0.05) associated with litter-size traits. NRP2 might be a candidate gene for pig-litter size based on its chromosome location (Du et al., 2006), significant association with litter-size traits and relationships with Sema and the VEGF super families.     

An update on molecular genetic studies of human personality traits

Personality is a complex phenotype and people differ considerably when they are evaluated by self-report questionnaires. There is convincing evidence from twin studies that basic personality dimensions in men and women have a considerable genetic component. However, only recently have common genetic polymorphisms been associated with particular personality traits, especially the dopamine D4 receptor with novelty seeking and the serotonin transporter with anxiety-related traits or neuroticism. The current review examines progress in the past few years in molecular personality genetics and focuses on the reasons for difficulties in replicating first findings as well as the prospects for future studies in this area. The molecular genetic structure of human personality is worth studying both for its intrinsic interest in helping us to understand individual differences in human behaviour and the light it will shed on more complex behavioural disorders that are likely to partially share some common genetic variants.     

The Quantitative Genetics of Phenotypic Robustness

Phenotypic robustness, or canalization, has been extensively investigated both experimentally and theoretically. However, it remains unknown to what extent robustness varies between individuals, and whether factors buffering environmental variation also buffer genetic variation. Here we introduce a quantitative genetic approach to these issues, and apply this approach to data from three species. In mice, we find suggestive evidence that for hundreds of gene expression traits, robustness is polymorphic and can be genetically mapped to discrete genomic loci. Moreover, we find that the polymorphisms buffering genetic variation are distinct from those buffering environmental variation. In fact, these two classes have quite distinct mechanistic bases: environmental buffers of gene expression are predominantly sex-specific and trans-acting, whereas genetic buffers are not sex-specific and often cis-acting. Data from studies of morphological and life-history traits in plants and yeast support the distinction between polymorphisms buffering genetic and environmental variation, and further suggest that loci buffering different types of environmental variation do overlap with one another. These preliminary results suggest that naturally occurring polymorphisms affecting phenotypic robustness could be abundant, and that these polymorphisms may generally buffer either genetic or environmental variation, but not both.     

A genetic perspective on coeliac disease

Coeliac disease is an inflammatory disorder of the small intestine with an autoimmune component and strong heritability. Genetic studies have confirmed strong association to HLA and identified 39 nonHLA risk genes, mostly immune-related. Over 50% of the disease-associated single nucleotide polymorphisms are correlated with gene expression. Most of the coeliac disease-associated regions are shared with other immune-related diseases, as well as with metabolic, haematological or neurological traits, or cancer. We review recent progress in the genetics of coeliac disease and describe the pathways these genes are in, the functional consequences of the associated markers on gene expression and the genes shared between coeliac disease and other traits.     

Mechanisms and control of meiotic recombination in the yeast Saccharomyces cerevisiae

Recent studies in Saccharomyces cerevisiae have provided new insights in our understanding of the molecular mechanisms of meiotic recombination. Meiosis-specific DNA double-strand breaks have been detected and have been shown to be the lesions that initiate recombination events. These are located mostly in promoter regions where the chromatin is in an open configuration, and cluster in domains along the chromosome. They are likely to be made by a topoisomerase II-like protein encoded by the SPO11 gene. Several DNA intermediates in the meiotic double strand-break repair pathway have been characterised and several multi-protein complexes have been identified and shown to be involved at different steps in the repair pathway. The conservation of these protein complexes in higher eukaryotes suggests that the meiotic recombination mechanism could be conserved. With the application of the well characterised genetical, molecular, cytological and biochemical techniques and the recently developed technology for genomic studies (biochips), we can expect a rapid increase in our comprehension of the meiotic recombination process.     

Gene polymorphisms and chronic obstructive pulmonary disease

The genetic component was suggested to contribute to the development of chronic obstructive pulmonary disease (COPD), a major and growing public health burden. The present review aims to characterize the evidence that gene polymorphisms contribute to the aetiology of COPD and related traits, and explore the potential relationship between certain gene polymorphisms and COPD susceptibility, severity, lung function, phenotypes, or drug effects, even though limited results from related studies lacked consistency. Most of these studies were association studies, rather than confirmatory studies. More large‐sized and strictly controlled studies are needed to prove the relationship between gene polymorphisms and the reviewed traits. More importantly, prospective confirmatory studies beyond initial association studies will be necessary to evaluate true relationships between gene polymorphisms and COPD and help individualized treatment for patients with COPD.