A Caenorhabditis elegans Wild Type Defies the Temperature–Size Rule Owing to a Single Nucleotide Polymorphism in tra-3

Ectotherms rely for their body heat on surrounding temperatures. A key question in biology is why most ectotherms mature at a larger size at lower temperatures, a phenomenon known as the temperature–size rule. Since temperature affects virtually all processes in a living organism, current theories to explain this phenomenon are diverse and complex and assert often from opposing assumptions. Although widely studied, the molecular genetic control of the temperature–size rule is unknown. We found that the Caenorhabditis elegans wild-type N2 complied with the temperature–size rule, whereas wild-type CB4856 defied it. Using a candidate gene approach based on an N2 × CB4856 recombinant inbred panel in combination with mutant analysis, complementation, and transgenic studies, we show that a single nucleotide polymorphism in tra-3 leads to mutation F96L in the encoded calpain-like protease. This mutation attenuates the ability of CB4856 to grow larger at low temperature. Homology modelling predicts that F96L reduces TRA-3 activity by destabilizing the DII-A domain. The data show that size adaptation of ectotherms to temperature changes may be less complex than previously thought because a subtle wild-type polymorphism modulates the temperature responsiveness of body size. These findings provide a novel step toward the molecular understanding of the temperature–size rule, which has puzzled biologists for decades

Genotype-dependent lifespan effects in peptone deprived Caenorhabditis elegans

Dietary restriction appears to act as a general non-genetic mechanism that can robustly prolong lifespan. There have however been reports in many systems of cases where restricted food intake either shortens, or does not affect, lifespan. Here we analyze lifespan and the effect of food restriction via deprived peptone levels on lifespan in wild isolates and introgression lines (ILs) of the nematode Caenorhabditis elegans. These analyses identify genetic variation in lifespan, in the effect of this variation in diet on lifespan and also in the likelihood of maternal, matricidal, hatching. Importantly, in the wild isolates and the ILs, we identify genotypes in which peptone deprivation mediated dietary restriction reduces lifespan. We also identify, in recombinant inbred lines, a locus that affects maternal hatching, a phenotype closely linked to dietary restriction in C. elegans. These results indicate that peptone deprivation mediated dietary restriction affects lifespan in C. elegans in a genotype-dependent manner, reducing lifespan in some genotypes. This may operate by a mechanism similar to dietary restriction

Caenorhabditis elegans behavioral genetics: where are the knobs?

Thousands of behavioral mutants of Caenorhabditis elegans have been studied. I suggest a set of criteria by which some genes important in the evolution of behavior might be recognized, and identify neuropeptide signaling pathways as candidates

Cancer risks associated with germline PALB2 pathogenic variants: An international study of 524 families

PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers

Populations under stress : analysis on the interface between ecology and evolutionary genetics in nematodes

Human activities increasingly affect the natural environment. Consequently, many organisms are confronted with environmental conditions different from the ones they evolved in and experience stress. Environmental stress affects various levels of biological organization (e.g. cell, life-histories, population, community, ecosystem) and concerns various time-spans. Therefore, to understand the mechanisms behind stress responses and the consequences for natural systems requires incorporation of multiple scientific disciplines.In this thesis I incorporate the frameworks of ecology and evolutionary genetics to investigate the effects of long-term stress on natural populations. In addition, I provide the resources to study genetic basis of stress-related traits within QTL approach. Nematodes were selected as the research subjects because of their wide distribution, importance for major ecological processes, such as decomposition, and the ease of laboratory handlings and genetic analysis.The major part of the presented research focused on the long-term effects of copper and pH stress on natural populations of the parthenogenetic nematode Acrobeloides nanus . Chapters 2, 3 and 4 present an extensive analysis of the populations from an experimental field where copper and pH treatments were applied in a factorial design approximately 20 years ago. At first, I considered effects of the combined stressors on population biomass and functional parameters such as secondary production and biomass turnover rate. Despite the fact that multiple anthropogenic stressors are common in human-dominated environment, the knowledge of their possible synergistic effects on population-level parameters is very limited. The investigation reported in chapter 2 is possibly the first study using a controlled experimental system in the field to disentangle the interactive effects of stressors on population parameters. The results indicated negative synergistic effects of high copper level and low pH on population secondary production and biomass turnover in A. nanus . Surprisingly, the biomass of A. nanus showed no negative effects under the same conditions. Overall, these findings demonstrated the impact of interactive stress effects and suggested that functional population parameters might be more sensitive to combination of stressors than the measures such as biomass or population abundance. Consequently, I concluded that realistic risk assessment would benefit from the analyses of combined stressors effects and incorporation of functional population measures. In chapter 3, I focused on the question whether the observed changes in life-history traits in A. nanus were the result of adaptation to local copper and pH conditions. Reciprocal transplant- and reaction norm experiments indicated that the populations from two extreme stress treatments underwent adaptive divergence within approximately 20 years of exposure. I interpreted these results from the perspective of evolutionary biology of asexual species and concluded that they contradict the general view of low adaptive potential of asexual eukaryotes. They also demonstrate that the population structure and distribution of asexual species might be shaped by local adaptation events. In chapter 4, I tested whether the adaptive changes in life-history traits of A. nanus were accompanied by underlying changes in genetic architecture represented by genetic variance-covariance matrix ( G ). Within evolutionary genetics, the concept of G matrix is central as it provides the framework for the analysis of phenotypic evolution under the assumption of G stability over time. It is acknowledged that genetic drift or strong selection such as stress might lead to evolution of G matrices, however the time-spans and conditions promoting these changes in natural populations remain unknown. The comparisons of G matrices for life-history traits of A. nanus indicated a profound divergence of G structure as a response to divergent selection imposed by field treatments and pointed to a less distinct divergence of G matrices within the treatments that are likely to be attributed to drift. Because all the detected changes took place within 20 years of the existence of the experimental field, I concluded that genetic architecture might evolve rapidly in natural populations. These results suggest also that strong stress might enhance this process and that the observed high dynamics of G structure is likely to represent a general feature of asexual species.The second part of the presented research concerned the genetic bases of stress-related and other complex traits in Caenorhabditis elegans . Although there is a growing interest for incorporating QTL methods to the mainstream genetic approaches in this model species, the lack of powerful resources hampers the advancements within this field. In chapter 5, I reported the construction of a permanent, genome-wide library of near-isogenic lines (NILs) from two parental lines, the Hawaiian line CB4856 and theBristolline N2. All of the 91 NILs have a single, short and homozygous segment of the CB4856 genome introgressed into N2 background and in total the introgressed segments cover at least 95% of the genome length. In the same chapter, I presented the analysis of one of the stress-related traits in C. elegans , clumping behaviour, using both recombinant inbred lines (RILs) and selected NILs which resulted in detection of a novel locus responsible for natural phenotypic variation in this trait. Overall, I concluded that the properties of this library allow for more efficient and accurate QTL localization and facilitate gene identification.In chapter 6, I discussed the most relevant findings reported in this thesis and considered them in the context of fundamental problems (evolution of sexual reproduction) and applied issues (the use of clonal organisms for toxicity testing). I devoted also one section of this chapter to discuss the role of QTL mapping in stress-related research. Finally, I made some suggestions regarding future research directions and risk assessment strategies

The effect of developmental nutrition on life span and fecundity depends on the adult reproductive environment in Drosophila melanogaster

Both developmental nutrition and adult nutrition affect life-history traits; however, little is known about whether the effect of developmental nutrition depends on the adult environment experienced. We used the fruit fly to determine whether life-history traits, particularly life span and fecundity, are affected by developmental nutrition, and whether this depends on the extent to which the adult environment allows females to realize their full reproductive potential. We raised flies on three different developmental food levels containing increasing amounts of yeast and sugar: poor, control, and rich. We found that development on poor or rich larval food resulted in several life-history phenotypes indicative of suboptimal conditions, including increased developmental time, and, for poor food, decreased adult weight. However, development on poor larval food actually increased adult virgin life span. In addition, we manipulated the reproductive potential of the adult environment by adding yeast or yeast and a male. This manipulation interacted with larval food to determine adult fecundity. Specifically, under two adult conditions, flies raised on poor larval food had higher reproduction at certain ages – when singly mated this occurred early in life and when continuously mated with yeast this occurred during midlife. We show that poor larval food is not necessarily detrimental to key adult life-history traits, but does exert an adult environment-dependent effect, especially by affecting virgin life span and altering adult patterns of reproductive investment. Our findings are relevant because (1) they may explain differences between published studies on nutritional effects on life-history traits; (2) they indicate that optimal nutritional conditions are likely to be different for larvae and adults, potentially reflecting evolutionary history; and (3) they urge for the incorporation of developmental nutritional conditions into the central life-history concept of resource acquisition and allocatio

Yielding and profitability of starchy potatoes cultivation in individual farm

Celem badań było zaprezentowanie plonowania i opłacalności uprawy ziemniaków skrobiowych w gospodarstwie indywidualnym w latach 2014-2015. Dane pochodziły z gospodarstwa rolnego położonego we wsi Nosów, gmina Leśna Podlaska specjalizującego się w produkcji ziemniaków skrobiowych współpracującego z PPS ”PEPEES” w Łomży. Większy plon ogólny bulw ziemniaków skrobiowych uzyskano w 2014 roku, a wartość produkcji z 1 ha w poszczególnych latach była zróżnicowana i wynosiła odpowiednio 10394 i 6717 zł. Duża zmienność przychodu w poszczególnych latach była podyktowana wysokością plonu i różną ceną uzyskaną za jednostkę produkcji. O opłacalności uprawy ziemniaków skrobiowych decydowały koszty bezpośrednie. Największe koszty bezpośrednie stanowiły koszty związane zakupem sadzeniaków. Wyższą opłacalność uprawy ziemniaków skrobiowych uzyskano w 2014 roku.The aim of the study was to present the yield and profitability of starch potato cultivation in an individual farm in 2014-2015. The data came from a farm located in the village of Nosow, the borough of Lesna Podlaska, specializing in the production of starch potato cooperating with PPS „PEPEES” in Lomza. Total yield of tubers of potato starch was higher in 2014, and the production value of 1 ha in different years was varied and amounted to 10394 and 6717 PLN, respectively. The fluctuations in revenue in particular years were caused by the crop yield and the price per unit of production. The profitability of starch potato cultivation depended on the direct costs, particularly the cost of purchasing seed potatoes. Higher profitability of starch potato was achieved in 2014

Beyond induced mutants: using worms to study natural variation in genetic pathways

Induced mutants in the nematode Caenorhabditis elegans are used to study genetic pathways of processes ranging from aging to behavior. The effects of such mutations are usually analyzed in a single wildtype background: N2. However, studies in other species demonstrate that the phenotype(s) of induced mutations can vary widely depending on the genetic background. Moreover, induced mutations in one genetic background do not reveal the allelic effects that segregate in natural populations and contribute to phenotypic variation. Because other wildtype Caenorhabditis spp., including C. elegans, are now available, we review how current mapping resources and methodologies within and between species support the use of Caenorhabditis spp. for studying genetic variation, with a focus on pathways associated with human disease

Beyond induced mutants: using worms to study natural variation in genetic pathways

Induced mutants in the nematode Caenorhabditis elegans are used to study genetic pathways of processes ranging from aging to behavior. The effects of such mutations are usually analyzed in a single wildtype background: N2. However, studies in other species demonstrate that the phenotype(s) of induced mutations can vary widely depending on the genetic background. Moreover, induced mutations in one genetic background do not reveal the allelic effects that segregate in natural populations and contribute to phenotypic variation. Because other wildtype Caenorhabditis spp., including C. elegans, are now available, we review how current mapping resources and methodologies within and between species support the use of Caenorhabditis spp. for studying genetic variation, with a focus on pathways associated with human disease