Biology subjects

Kreitman, M.

Publications and source records attributed to Kreitman, M..

5 recordsLinked to original sources

bioRxiv2026

Outbred Drosophila populations reveal diet-dependent genetic effects on development time

Metabolic effects of genetic variation often depend on diet, yet the loci underlying diet-dependent developmental responses remain incompletely defined. Here we combine multi-trait phenotyping of Drosophila Genetic Reference Panel lines with genome-wide mapping in newly developed Drosophila Recombinant Populations. High sugar causes genotype- and life-stage-dependent changes in metabolic and life-history traits, with development time emerging as a highly heritable, sugar-sensitive phenotype. Mapping in 16 outbred advanced intercross populations reveals distinct association landscapes under low- and high-sugar diets, with a concentrated low-sugar signal, a more distributed high-sugar pattern, and identified genotype-by-diet loci including tap, Eip75B and Cerk. Functional perturbation supports diet-dependent effects for several prioritized candidates. Allele-frequency analyses identify operationally defined thrifty-like variants associated with delayed development under high sugar and relatively earlier development under low sugar; these variants are enriched for cell-adhesion, neurodevelopmental, and morphogenetic processes. Together, these results establish an outbred Drosophila framework for dissecting how dietary sugar remodels the genetic architecture of development time.

genetics↗

bioRxiv2021

Gap genes are involved in inviability in hybrids between Drosophila melanogaster and D. santomea

Evolved changes within species can lead to the loss of viability in hybrids. Inviability is also a convenient phenotype to genetically map and validate functionally divergent genes and pathways differentiating closely related species. Here, I identify the Drosophila melanogaster form of the highly conserved essential gap gene giant (gt) as a key genetic determinant of inviability in hybrids with D. santomea. The presence of this allele is sufficient and necessary to cause a prevalent abdominal ablation in the developing hybrid embryo. Further genetic analysis indicates that tailless (tll), another gap gene, is also involved in the hybrid defects. giant and tll are both members of the gap gene network of transcription factors that participate in establishing anterior-posterior specification of the dipteran embryo, a highly conserved developmental process. I found no evidence for positive selection in either of the two genes. Genes whose outputs in this process are functionally conserved nevertheless evolve over short timescales to cause inviability in hybrids. SIGNIFICANCE STATEMENTHybrid organisms--which have parents from different species--are usually less healthy than pure-species organisms. Hybrid inviability is an extreme example of this phenomenon. Defects result from incompatibilities between genes that have diverged in the parental species. In this piece, I dissect the genetic basis of hybrid inviability between two species of Drosophila: D. melanogaster and D. santomea. I identified two genes, gt and tll responsible for the inviability in these hybrids. The two genes belong to the gap gene network, a highly conserved pathway that is in charge of establishing embryonic polarity in insects. These results show that developmentally important genes might evolve sufficiently fast to cause hybrid inviability in species that still can interbreed.

evolutionary biology↗

bioRxiv2021

Rapid evolution of the functionally conserved gap gene giant in Drosophila

Developmental processes in multicellular organisms, and the outcomes they produce, are often evolutionarily conserved. Yet phylogenetic conservation of developmental outcomes is not reflected in functional preservation of the genes regulating these processes, a phenomenon referred to as developmental system drift (1, 2). Little is known about the evolutionary forces producing change in the molecular details of regulatory genes and their networks while preserving development outcomes. Here we address this void in knowledge by systematically swapping the Drosophila melanogaster coding and noncoding regions of the essential gap gene, giant, a key regulator of embryonic pattern formation, with orthologous sequences drawn from both closely and distantly related species within the genus. Employing sensitized genetic complementation assays, the loss of a transgenes ability to restore viability occurs across phylogeny at every interspecific level of comparison and includes both coding and noncoding changes. Epistasis is present as well -- both between coding and noncoding sequences and, in a dramatic example of change-of-sign epistasis, between the only two coding substitutions separating two very closely related species. A continuous process of functional divergence hidden under conserved phylotypic developmental outcomes requires reconsideration of the prevailing view that the essential genes in conserved regulatory networks are protected from the driving forces of evolutionary change.

evolutionary biology↗

bioRxiv2019

Population genetics of the highly polymorphic RPP8 gene family

Plant NLR resistance genes provide some of the most extreme examples of polymorphism in eukaryotic genomes, rivalling even the vertebrate major histocompatibility complex. Surprisingly, this is also true in Arabidopsis thaliana, a predominantly selfing species with low heterozygosity. Here, we investigate how gene duplication and intergenic exchange contribute to this extraordinary variation. RPP8 is a three-locus system that is configured chromosomally as either a direct-repeat tandem duplication or as a single copy locus, plus a locus 2 Mb distant. We sequenced 48 RPP8 alleles from 37 accessions of A. thaliana and 12 RPP8 alleles from A. lyrata to investigate the patterns of interlocus shared variation. The tandem duplicates display fixed differences and share less variation with each other than either shares with the distant paralog. A high level of shared polymorphism among alleles at one of the tandem duplicates, the single-copy locus and the distal locus, must involve both classical crossing over and intergenic gene conversion. Despite these polymorphism-enhancing mechanisms, the observed nucleotide diversity could not be replicated under neutral forward-in-time simulations. Only by adding balancing selection to the simulations do they approach level of polymorphism observed at RPP8. In this NLR gene triad, genetic architecture, gene function and selection all combine to generate diversity.

evolutionary biology↗

bioRxiv2018

The relationship between robustness and evolution

Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic mutations. Given the large divergence in phenotype across species, understanding the relationship between high robustness and evolvability has been of interest to both theorists and experimentalists. Although canalization was originally proposed in the context of multicellular organisms, the effect of multicellularity on evolvability has not been considered by theoreticians. We address this issue using a Boolean population model with explicit representation of an environment in which multicellular individuals with explicit genotype and phenotype evolve. Robustness is described by a single real number between zero and one. We find that high robustness is favored in constant environments, and lower robustness is favored after environmental change. Multicellularity severely constrains robustness: peak evolvability occurs at an absolute level of robustness of about 0.99 compared with values of about 0.5 in a classical neutral network model. Multicellularity results in a sharp peak of evolvability in which the maximum is set by the fact that the fixation of adaptive mutations becomes more improbable as robustness decreases. When robustness is put under genetic control, robustness levels leading to maximum evolvability are selected for, but maximal relative fitness appears to require recombination.

evolutionary biology↗