scholarly journals Evolutionary genetic integration of behavioural and endocrine components of the stress response

2019 ◽  
Author(s):  
T.M. Houslay ◽  
R.L. Earley ◽  
S.J. White ◽  
W. Lammers ◽  
A.J. Grimmer ◽  
...  

AbstractThe vertebrate stress response comprises a suite of behavioural and physiological traits that must be functionally integrated to ensure organisms cope adaptively with acute stressors. The expectation that natural selection has favoured functional integration leads to a prediction of genetic integration: genetic variation in the stress response should include covariation between its component behavioural and physiological traits. Despite the implications of such genetic integration for our understanding of human and animal health, as well as evolutionary responses to natural and anthropogenic stressors, formal quantitative genetic tests of this prediction are lacking. Here we demonstrate that Trinidadian guppies (Poecilia reticulata) show genetic variation in a suite of behavioural and physiological components of the acute stress response, and that these are indeed integrated into a single major axis of genetic variation. This axis appears to reflect continuous variation in the magnitude of integrated stress responsiveness, rather than variation in ‘coping style’ (a verbal model that postulates equal levels of stress responsiveness will manifest differently across individuals). The genetic integration we find here could either facilitate or constrain evolutionary responses to selection, depending upon the extent to which the direction of selection aligns with this single major axis of genetic covariation among stress response traits. Such integration also suggests that, while stress-related disease typically arises from physiological components of the stress response, selection on the genetically correlated behavioural responses to stress could offer a viable non-invasive route to the genetic improvement of health and welfare in captive animal populations.

2021 ◽  
Author(s):  
◽  
Mariah Taylor ◽  

Two RNA virus families that pose a threat to human and animal health are Hantaviridae and Coronaviridae. These RNA viruses which originate in wildlife continue and will continue to cause disease, and hence, it is critical that scientific research define the mechanisms as to how these viruses spillover and adapt to new hosts to become endemic. One gap in our ability to define these mechanisms is the lack of whole genome sequences for many of these viruses. To address this specific gap, I developed a versatile amplicon-based whole-genome sequencing (WGS) approach to identify viral genomes of hantaviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within reservoir and spillover hosts. In my research studies, I used the amplicon-based WGS approach to define the genetic plasticity of viral RNA within pathogenic and nonpathogenic hantavirus species. The standing genetic variation of Andes orthohantavirus and Prospect Hill orthohantavirus was mapped out and amino acid changes occurring outside of functional domains were identified within the nucleocapsid and glycoprotein. I observed several amino acid changes in functional domains of the RNA-dependent RNA polymerase, as well as single nucleotide polymorphisms (SNPs) within the 3’ non-coding region (NCR) of the S-segment. To identify whether virus adaptation would occur within the S- and L-segments we attempted to adapt hantaviruses in vitro in a spillover host model through passaging experiments. In early passages we identified few mutations in the M-segment with the majority being identified in the S-segment 3’ NCR and the L-segment. This work suggests that hantavirus adaptation occurs in the S- and L-segments although the effect of these mutants on pathology is yet to be determined. While sequencing laboratory isolates is easily accomplished, sequencing low concentrations of virus within the reservoir is a formidable task. I further translated our amplicon-based WGS approach into a pan-oligonucleotide amplicon-based WGS approach to sequence hantavirus vRNA and mRNA from reservoir and spillover hosts in Ukraine. This approach successfully identified a novel Puumala orthohantavirus (PUUV) strain in Ukraine and using Bayesian phylogenetics we found this strain to be associated with the PUUV Latvian lineage. Early during the SARS-CoV-2 pandemic, I applied the knowledge gained in the hantavirus WGS efforts to sequencing of SARS-CoV-2 from nasopharyngeal swabs collected in April 2020. The genetic diversity of 45 SARS-CoV-2 isolates was evaluated with the methods I developed. We identified D614G, a notable mutation known for increasing transmission, in over 90% of our isolates. Two major lineages distinguish SARS-CoV-2 variants worldwide, lineages A and B. While most of our isolates were found within B lineage, we also identified one isolate within lineage A. We performed in vitro work which confirmed A lineage isolates as having poor replication in the trachea as compared to the nasal cavity. Five of these isolates presented a unique array of mutations which were assessed in the keratin 18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model for its response immunologically and pathogenically. We identified a distinction of pathogenesis between the A and B lineages with emphysema being common amongst A lineage isolates. Additionally, we discovered a small cohort of likely SNPs that defined the late induction of eosinophils during infection. In summary, this work will further define the dynamics of genetic variation and plasticity within virus populations that cause disease outbreaks and will allow a deeper understanding of the virus-host relationship.


2018 ◽  
Vol 46 (2) ◽  
pp. 2597-2597
Author(s):  
Ahmed Sallam ◽  
Ahmed Amro ◽  
Ammar Elakhdar ◽  
Mona F. A. Dawood ◽  
Toshihiro Kumamaru ◽  
...  

2021 ◽  
Author(s):  
Nikki D. Russell ◽  
Clement Y. Chow

AbstractGenotype x Environment (GxE) interactions occur when environmental conditions drastically change the effect of a genetic variant. In order to truly understand the effect of genetic variation, we need to incorporate multiple environments into our analyses. Many variants, under steady state conditions, may be silent or even have the opposite effect under stress conditions. This study uses an in vivo mouse model to investigate how the effect of genetic variation changes with tissue type and cellular stress. Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. This triggers the unfolded protein response (UPR), a large transcriptional response which attempts to return the cell to homeostasis. This transcriptional response, despite being a well conserved, basic cellular process, is highly variable across different genetic backgrounds, making it an ideal system to study GxE effects. In this study, we sought to better understand how genetic variation alters expression across tissues, in the presence and absence of ER stress. The use of different mouse strains and their F1s allow us to also identify context specific cis- and trans-regulatory mechanisms underlying variable transcriptional responses. We found hundreds of genes that respond to ER stress in a tissue- and/or genotype-dependent manner. Genotype-dependent ER stress-responsive genes are enriched for processes such as protein folding, apoptosis, and protein transport, indicating that some of the variability occurs in canonical ER stress factors. The majority of regulatory mechanisms underlying these variable transcriptional responses derive from cis-regulatory variation and are unique to a given tissue or ER stress state. This study demonstrates the need for incorporating multiple environments in future studies to better elucidate the effect of any particular genetic factor in basic biological pathways, like the ER stress response.Author SummaryThe effect of genetic variation is dependent on environmental context. Here we use genetically diverse mouse strains to understand how genetic variation interacts with stress state to produce variable transcriptional profiles. In this study, we take advantage of the endoplasmic reticulum (ER) stress response which is a large transcriptional response to misfolded proteins. Using this system, we uncovered tissue- and ER stress-specific effects of genetic variation on gene expression. Genes with genotype-dependent variable expression levels in response to ER stress were enriched for canonical ER stress functions, such as protein folding and transport. These variable effects of genetic variation are driven by unique sets of regulatory variation that are only active under context-specific circumstances. The results of this study highlight the importance of including multiple environments and genetic backgrounds when studying the ER stress response and other cellular pathways.


2016 ◽  
Vol 15 (6) ◽  
pp. 539-547 ◽  
Author(s):  
P. Sharma ◽  
S. Sareen ◽  
M. Saini ◽  
Shefali

AbstractHeat stress greatly limits the productivity of wheat in many regions. Knowledge on the degree of genetic diversity of wheat varieties along with their selective traits will facilitate the development of high yielding, stress-tolerant wheat cultivar. The objective of this study were to determine genetic variation in morpho-physiological traits associated with heat tolerance in 30 diverse wheat genotypes and to examine genetic diversity and relationship among the genotypes varying heat tolerance using molecular markers. Phenotypic data of 15 traits were evaluated for heat tolerance under non-stress and stress conditions for two consecutive years. A positive and significant correlation among cell membrane stability, canopy temperature depression, biomass, susceptibility index and grain yield was shown. Genetic diversity assessed by 41 polymorphic simple sequence repeat (SSR) markers was compared with diversity evaluated for 15 phenotypic traits averaged over stress and non-stress field conditions. The mean polymorphic information content for SSR value was 0.38 with range of 0.12–0.75. Based on morpho-physiological traits and genotypic data, three groups were obtained based on their tolerance (HHT, MHT and LHT) levels. Analysis of molecular variance explained 91.7% of the total variation could be due to variance within the heat tolerance genotypes. Genetic diversity among HHT was higher than LHT genotypes and HHT genotypes were distributed among all cluster implied that genetic basis of heat tolerance in these genotypes was different thereby enabling the wheat breeders to combine these diverse sources of genetic variation to improve heat tolerance in wheat breeding programme.


Parasitology ◽  
2014 ◽  
Vol 141 (9) ◽  
pp. 1148-1155 ◽  
Author(s):  
ANKIT K. ROCHANI ◽  
CHANDAN MITHRA ◽  
MEETALI SINGH ◽  
UTPAL TATU

SUMMARYTrypanosomiasis is caused by Trypanosoma species which affect both human and animal populations and pose a major threat to developing countries. The incidence of animal trypanosomiasis is on the rise. Surra is a type of animal trypanosomiasis, caused by Trypanosoma evansi, and has been included in priority list B of significant diseases by the World Organization of Animal Health (OIE). Control of surra has been a challenge due to the lack of effective drugs and vaccines and emergence of resistance towards existing drugs. Our laboratory has previously implicated Heat shock protein 90 (Hsp90) from protozoan parasites as a potential drug target and successfully demonstrated efficacy of an Hsp90 inhibitor in cell culture as well as a pre-clinical mouse model of trypanosomiasis. This article explores the role of Hsp90 in the Trypanosoma life cycle and its potential as a drug target. It appears plausible that the repertoire of Hsp90 inhibitors available in academia and industry may have value for treatment of surra and other animal trypanosomiasis.


2008 ◽  
Vol 42 ◽  
pp. 49-65 ◽  
Author(s):  
C. Nimbkar ◽  
J. Gibson ◽  
M. Okeyo ◽  
P. Boettcher ◽  
J. Soelkner

SummarySustainable use of animal genetic resources for agriculture and food production is proposed as the best strategy for maintaining their diversity. Achievement of sustainable use would continue to support livelihoods and minimize the long-term risk for survival of animal populations. The concept of sustainable use has economic, environmental and socio-cultural dimensions. Sustainable use of animal genetic resources also contributes to food security, rural development, increasing employment opportunities and improving standards of living of keepers of breeds. Supporting the rearing of breeds through better infrastructure, services, animal health care, marketing opportunities and other interventions would make a significant contribution to the sustainable use of animal genetic resources.Sustainable use envisages the use and improvement of breeds that possess high levels of adaptive fitness to the prevailing environment. It also encompasses the deployment of sound genetic principles for sustainable development of the breeds and the sustainable intensification of the production systems themselves. Sustainable use and genetic improvement rely on access to a wide pool of genetic resources.Genetic improvement programmes need to be considered in terms of national agriculture and livestock development objectives, suitability to local conditions and livelihood security as well as environmental sustainability. Genetic improvement can involve choice of appropriate breeds, choice of a suitable pure breeding or crossbreeding system and application of within-breed genetic improvement. The choice of appropriate breeds and crossbreeding systems in developed countries has been a major contributor to the large increases in productivity, and has benefited greatly from the fact that developed country animal genetic resources are well characterized and relatively freely exchanged. Where proper steps have been followed by careful assessment of demand, execution, delivery, impact and cost-benefit analyses, successful within-breed improvement has been realized within indigenous populations in developing countries. Breeding objectives and programmes for subsistence oriented and pastoralist systems are likely to be entirely different from conventional programmes. Crossbreeding has been most successful where it is followed by a rigorous selection programme involving livestock owners' participation and substantial public sector investment in the form of technical support. In any genetic improvement programme, inbreeding needs to be monitored and controlled.Within-breed genetic improvement is normal practice in the developed world, and has become a highly technical enterprise, involving a range of reproduction, recording, computing and genomic technologies. Emerging genomic technologies promise the ability to identify better, use and improve developing world animal genetic resources in the foreseeable future. Useful systems can, however, be established without the need for application of advanced technology or processes.


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