Bite force performance from wild derived mice has undetectable heritability despite having heritable morphological components

Fitness-related traits tend to have low heritabilities. Conversely, morphology tends to be highly heritable. Yet, many fitness-related performance traits such as running speed or bite force depend critically on morphology. Craniofacial morphology correlates with bite performance in several groups including rodents. However, within species, this relationship is less clear, and the genetics of performance, morphology and function are rarely analyzed in combination. Here, we use a half-sib design in outbred wild-derived Mus musculus to study the morphology-bite force relationship and determine whether there is additive genetic (co-)variance for these traits. Results suggest that bite force has undetectable additive genetic variance and heritability in this sample, while morphological traits related mechanically to bite force exhibit varying levels of heritability. The most heritable traits include the length of the mandible which relates to bite force. Despite its correlation with morphology, realized bite force was not heritable, which suggests it is less responsive to selection in comparison to its morphological determinants. We explain this paradox with a non-additive, many-to-one mapping hypothesis of heritable change in complex traits. We furthermore propose that performance traits could evolve if pleiotropic relationships among the determining traits are modified.

Potential of Mutation Breeding to Sustain Food Security

Mutation is a sudden heritable change in the genetic material of living organism. Spontaneous mutation, the natural process that develops new allele copies of a gene was the only source of genetic diversity until the 20th century. Besides, mutations can also be induced artificially using physical or chemical mutagens. Chemical mutations received popularity due to its efficiency in creating gene mutations contrary to chromosomal changes. Mutation has played a vital role in the improvement of crop productivity and quality, resultantly > 3,000 varieties of 175 plant species have been developed either through direct or indirect induced mutation breeding approaches worldwide. The advances in plant breeding also achieved through molecular marker technology. The in vitro mutagenesis, heavy-ion beam, and space mutation breeding are being efficiently used to create genetic variability to improve various complicated traits in crop plants. In mutation breeding, TILLING (Targeting Induced Local Lesions in Genomes), a more advanced molecular technique is being used to identify specific sequential genomic changes in mutant plants. Therefore, the mutation breeding in combination with molecular techniques could be an efficient tool in plant breeding programs. This chapter will discuss and review the mutation breeding application for the improvement of crop productivity and environmental stresses.

The genetics of morphological and behavioural island traits in deer mice

Animals on islands often exhibit dramatic differences in morphology and behaviour compared with mainland individuals, a phenomenon known as the ‘island syndrome’. These differences are thought to be adaptations to island environments, but the extent to which they have a genetic basis or instead represent plastic responses to environmental extremes is often unknown. Here, we revisit a classic case of island syndrome in deer mice ( Peromyscus maniculatus ) from British Columbia. We first show that Saturna Island mice and those from neighbouring islands are approximately 35% (approx. 5 g) heavier than mainland mice and diverged approximately 10 000 years ago. We then establish laboratory colonies and find that Saturna Island mice are heavier both because they are longer and have disproportionately more lean mass. These trait differences are maintained in second-generation captive-born mice raised in a common environment. In addition, island–mainland hybrids reveal a maternal genetic effect on body weight. Using behavioural testing in the laboratory, we also find that wild-caught island mice are less aggressive than mainland mice; however, laboratory-raised mice born to these founders do not differ in aggression. Together, our results reveal that these mice have different responses to the environmental conditions on islands—a heritable change in a morphological trait and a plastic response in a behavioural trait.

The Development of Epigenetics and Related Inhibitors for Targeted Drug Design in Cancer Therapy

Epigenetics process is the heritable change in gene function that does not involve changes in the DNA sequence. Until now, several types of epigenetic mechanisms have been characterized, including DNA methylation, histone modification (acetylation, methylation, etc.), nucleosome remodeling, and noncoding RNAs. With the biological investigations of these modifiers, some of them are identified as promoters in the process of various diseases, such as cancer, cardiovascular disease and virus infection. Epigenetic changes may serve as potential “first hits” for tumorigenesis. Hence, targeting epigenetic modifiers is being considered as a promising way for disease treatment. To date, six agents in two epigenetic target classes (DNMT and HDAC) have been approved by the US Food and Drug Administration (FDA). Most of these drugs are applied in leukemia, lymphoma therapy, or are combined with other drugs for the treatment of solid tumor. Due to the rapid development of epigenetics and epigenetics targeted drugs, it is becoming an emerging area in targeted drug design.

Patients Suffer While the Science Establishment Resists Innovative Therapies

Human gene therapy has been up to now of a type that affects only the patient being treated; it has not modified sperm or eggs cells or embryos in a way that would constitute “germ line gene therapy” (GLGT) by creating a heritable change and affecting future generations. Preclinical research has progressed almost to the point where GLGT interventions will be possible with a reasonable likelihood of success, but such clinical trials are currently prohibited: NIH's Recombinant DNA Advisory Committee is not permitted even to consider such proposals, and the FDA cannot use appropriated funds to review such trials. Such absolute prohibitions are bad for patients and bad public policy.

Transient Hsp90 suppression promotes a heritable change in protein translation

The heat shock protein 90 (Hsp90) chaperone functions as a protein-folding buffer and plays a unique role promoting the evolution of new heritable traits. To investigate the role of Hsp90 in modulating protein synthesis, we screened more than 1200 proteins involved in mRNA regulation for physical interactions with Hsp90 in human cells. Among the top hits was CPEB2, which strongly binds Hsp90 via its prion domain, reminiscent of the prion-like regulation of translation of Aplysia CPEB. In a yeast model of CPEB prion-dependent translation regulation, transient inhibition of Hsp90 amplified CPEB2 prion activity and resulted in persistent translation of the CPEB reporter. Remarkably, inhibition of Hsp90 was sufficient to induce a heritable change in protein translation that persisted for 30 generations, even in the absence of exogenous CPEB. Although we identified a variety of perturbations that enhanced translation of the reporter, only Hsp90 inhibition led to persistent activation. Thus, transient loss of Hsp90 function leads to the non-genetic inheritance of a novel translational state. We propose that, in addition to sculpting the conformational landscape of the proteome, Hsp90 promotes phenotypic variation by modulating protein synthesis.

Adaptive Significance of ERα Splice Variants in Killifish (Fundulus heteroclitus) Resident in an Estrogenic Environment

The possibility that chronic, multigenerational exposure to environmental estrogens selects for adaptive hormone-response phenotypes is a critical unanswered question. Embryos/larvae of killifish from an estrogenic-polluted environment (New Bedford Harbor, MA [NBH]) compared with those from a reference site overexpress estrogen receptor alpha (ERα) mRNA but are hyporesponsive to estradiol. Analysis of ERα mRNAs in the two populations revealed differences in splicing of the gene encoding ERα (esr1). Here we tested the transactivation functions of four differentially expressed ERα mRNAs and tracked their association with the hyporesponsive phenotype for three generations after transfer of NBH parents to a clean environment. Deletion variants ERαΔ6 and ERαΔ6–8 were specific to NBH killifish, had dominant negative functions in an in vitro reporter assay, and were heritable. Morpholino-mediated induction of ERαΔ6 mRNA in zebrafish embryos verified its role as a dominant negative ER on natural estrogen-responsive promoters. Alternate long (ERαL) and short (ERαS) 5′-variants were similar transcriptionally but differed in estrogen responsiveness (ERαS ≫ ERαL). ERαS accounted for high total ERα expression in first generation (F1) NBH embryos/larvae but this trait was abolished by transfer to clean water. By contrast, the hyporesponsive phenotype of F1 NBH embryos/larvae persisted after long-term laboratory holding but reverted to a normal or hyper-responsive phenotype after two or three generations, suggesting the acquisition of physiological or biochemical traits that compensate for ongoing expression of negative-acting ERαΔ6 and ERαΔ6–8 isoforms. We conclude that a heritable change in the pattern of alternative splicing of ERα pre-mRNA is part of a genetic adaptive response to estrogens in a polluted environment.