Building Bridges from Genome to Physiology Using Machine Learning and Experimental Evolution.

experimental evolution, with its well-defined selection protocols, has long supplied useful genetic material for the analysis of functional physiology. While there is a long tradition of interpreting the effects of large-effect mutants physiologically, identifying and interpreting gene-to-phenotype relationships has been challenging in the genomic era, with many labs not resolving how physiological traits are affected by multiple genes throughout the genome. experimental evolution has demonstrated that multiple phenotypes change because of the evolution of many loci across the genome, creating the scientific challenge of sifting out differentiated but noncausal loci for individual characters.

The effects of adaptation to urea on feeding rates and growth in larvae.

A collection of forty populations were used to study the phenotypic adaptation of larvae to urea-laced food. A long-term goal of this research is to map genes responsible for these phenotypes. This mapping requires large numbers of populations.

Patient-specific genomics and cross-species functional analysis implicate LRP2 in hypoplastic left heart syndrome.

Congenital heart diseases (CHDs), including hypoplastic left heart syndrome (HLHS), are genetically complex and poorly understood. Here, a multidisciplinary platform was established to functionally evaluate novel CHD gene candidates, based on whole-genome and iPSC RNA sequencing of a HLHS family-trio. Filtering for rare variants and altered expression in proband iPSCs prioritized 10 candidates.

Genomics of Early Cardiac Dysfunction and Mortality in Obese .

In experimental evolution, we impose functional demands on laboratory populations of model organisms using selection. After enough generations of such selection, the resulting populations constitute excellent material for physiological research. An intense selection regime for increased starvation resistance was imposed on 10 large outbred populations.

Effects of evolutionary history on genome wide and phenotypic convergence in Drosophila populations.

Background: Studies combining experimental evolution and next-generation sequencing have found that adaptation in sexually reproducing populations is primarily fueled by standing genetic variation. Consequently, the response to selection is rapid and highly repeatable across replicate populations. Some studies suggest that the response to selection is highly repeatable at both the phenotypic and genomic levels, and that evolutionary history has little impact.

Starvation but not locomotion enhances heart robustness in Drosophila.

Insects and vertebrates have multiple major physiological systems, each species having a circulatory system, a metabolic system, and a respiratory system that enable locomotion and survival in stressful environments, among other functions. Broadening our understanding of the physiology of Drosophila melanogaster requires the parsing of interrelationships among such major component physiological systems. By combining electrical pacing and flight exhaustion assays with manipulative conditioning, we have started to unpack the interrelationships between cardiac function, locomotor performance, and other functional characters such as starvation and desiccation resistance.

Experimental Evolution and Heart Function in Drosophila.

Drosophila melanogaster is a good model species for the study of heart function. However, most previous work on D. melanogaster heart function has focused on the effects of large-effect genetic variants.

Rapid divergence and convergence of life-history in experimentally evolved Drosophila melanogaster.

Laboratory selection experiments are alluring in their simplicity, power, and ability to inform us about how evolution works. A longstanding challenge facing evolution experiments with metazoans is that significant generational turnover takes a long time. In this work, we present data from a unique system of experimentally evolved laboratory populations of Drosophila melanogaster that have experienced three distinct life-history selection regimes.

Four steps toward the control of aging: following the example of infectious disease.

The biotechnological task of controlling human aging will evidently be complex, given the failure of all simple strategies for accomplishing this task to date. In view of this complexity, a multi-step approach will be necessary. One precedent for a multi-step biotechnological success is the burgeoning control of human infectious diseases from 1840 to 2000.