Esther Betran - US grants

[unreadable] DESCRIPTION (provided by applicant): Heteromorphic sex chromosomes determine males and females in many species and their study is of general interest. Understanding the biases in the generation of genes and functions with respect to sex chromosomes is of primary significance to explaining sexual dimorphism and sex chromosome evolution. The sex chromosomes are found to differentiate from a pair of autosomes; most of the Y chromosome degenerates, and the X chromosome develops dosage compensation. Two main types of biases in the generation of duplicates in relation to sex chromosomes have been observed (in human, mouse and D. melanogaster): new genes are recruited by the Y chromosome and duplicates escape the X chromosome. In particular, retroposition has revealed the directionality of the duplication and has helped us to reveal duplicates that escape the X chromosome. Many of these new duplicate genes have male specific function. So the bias in their location and expression pattern reveals that significant positive selection takes place when those genes become fixed in the population and when they acquire a gender specific promoter. This project proposes two objectives: [1] to study the function and role of selection in retrogenes newly relocated from X to autosome in D. melanogaster, and [2] to study how the acquisition of male specific promoter regions takes place in these newly relocated retrogenes in Drosophila. Data of polymorphism and divergence at the nucleotide level, mRNA expression information, P element transformation technology, homologous recombination, direct mutagenesis and the most up to date bioinformatics tools and molecular evolution software will be exploited to achieve these two objectives. [unreadable] [unreadable]

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

This Major Research Instrumentation (MRI)award funds the acquisition of a Genome Sequencer FLX System from 454 Life Sciences and Roche Applied Science to help meet the needs of an expanding group of genomics researchers at University of Texas Arlington and the surrounding vicinity. Genetic and genome analyses have achieved a central role in modern biological research and are widely regarded as the key area for scientific discovery in the 21st century. UTA is making major advances in this field, through both strategic hires and investment in infrastructure. Specifically, UTA has renovated a 10,000+ sq.ft space in the Department of Biology to house the Genome Biology Group (GBG) Core Facility, hired 12 genomics faculty over the last five years, and considerable investment in major research equipment. The 454 sequencer, now part of the facility infrastructure, can produce 400,000 DNA sequences of 200-400 bases (equivalent to ~100 million bases of total sequence) in a single 6-8 hour run to support interdisciplinary and inter-institutional collaborative efforts spanning UTA's Department of Biology, Department of Computer Science and Engineering, and School of Nursing. Specific areas of research interest include: environmental transcriptomics, transcriptional profiling of developing systems (e.g., xenopus oocyte models), coral biology, entomology, plant stress physiology, and many others. Results from the research projects will be disseminated through student and faculty presentations at regional and national meetings, and through publication of peer-reviewed journal articles.

DESCRIPTION (provided by applicant): The long-term objective of our research is to investigate the patterns that arise as a result of gene duplication to better understand the evolutionary forces that drive genome architecture. Meiotic sex chromosome inactivation (MSCI), the level of gene expression and sexual antagonism have been proposed to explain the patterns of duplication of male-biased genes in flies. However, MSCI or the level of expression cannot account for several observations, including the abundance of autosome-to-autosome duplicates;the observation that certain genes are duplicated while others are not even though all X-linked housekeeping genes should be under strong selective pressure to duplicate;the continued occurrence of gene duplications or the recurrence of duplications of some genes in the same lineage;or the loss of duplicated genes that evolved under positive selection. Additionally, most models of sexual antagonism do not incorporate gene duplication and instead propose that the dominance of the mutations can explain the location of sex-biased genes. Models that incorporate gene duplication do not consider that the sexually antagonistic selection begins with the parental gene (i.e., for parental alleles) and in autosomes and that it will continue after heteromorphic sex chromosomes and MSCI have evolved. An innovative model based on our results from the previous funding period is introduced in which gene duplication is considered to be an important mechanism to generate male germline functions and is proposed to resolve intralocus sexually antagonistic conflicts for housekeeping genes (i.e., selection operating already on the parental gene) driven by tissue antagonism (i.e., testis antagonism). It is now clear that the testes are subject to strong selection due to male competition, segregation distortion and/or parasite-related conflicts, and this is driving rapid evolution at the protein level and likely in regulatory regions. Under this model, gene turnover is also expected to be high. This project has three aims to study the function and antagonistic effects of new genes and parental genes as well as the evolutionary rate and structure of testes-specific regulatory regions. Aim 1 focuses on the function and role of testes-specific nuclear transport genes and their parental genes with respect to male germline conflicts. Aim 2 will investigate the antagonistic effects of a subset of the new testes-specific genes and parental nuclearly encoded mitochondrial gene variations. Aim 3 addresses the study of the rate of evolution of testes-specific regulatory regions and their potential bidirectional nature. Knockouts, knockdowns and tagged proteins will be used to study effects, interactions, cellular localization and co-expression of the genes. New genes or variants of parental genes will be expressed ectopically and the effects on fertility and lifespan will be studied. Whole genome polymorphism data from D. melanogaster and comparative genomics will be exploited using the most current bioinformatics tools and molecular evolution software to achieve these objectives. PUBLIC HEALTH RELEVANCE: In this proposal, we provide an original perspective on topics under intense study, such as patterns of gene duplication, sex-biased expression and the genomic location of sexually antagonistic traits and sexually dimorphic traits. We propose a novel hypothesis describing a new, overlooked role for gene duplication in the resolution of the intralocus sexually antagonistic conflict. The conceptual framework of current thinking on this topic will change if our thesis is supported, as this will imply that new sex-biased duplicate genes are often created from antagonistic alleles of housekeeping genes to resolve sexual antagonism driven by specialization and conflicts in sex-specific tissues.

Roundworm infections cause several debilitating diseases in both animals and agricultural plants, yet relatively little is known about the factors that regulate either the population dynamics and/or infectivity of most parasitic or free-living nematode species. This proposal aims to uncover the mechanisms by which a specific set of closely related roundworm species regulate the ratio of males, females, and/or infective/dispersive larval forms amongst their offspring. A combination of cellular, chemical and genetic approaches will be used. Broader impacts of the proposal studies include establishing research and student training links between a primarily undergraduate institution (William & Mary) and an institution with a large proportion of minority students (UT-Arlington). In addition, these studies may ultimately lead to new avenues for controlling roundworm infections.

Transposable elements (TEs) are DNA sequences capable of self-replication and mobility that often account for a substantial fraction of eukaryotic genomes. Despite their parasitic nature, it is now well documented that on many occasions the genes encoded by TEs, which normally facilitate their own propagation, have been "domesticated" to serve host cellular functions. The proposed work will test the general hypothesis that transposases are an opportune source of regulatory protein domains coopted because of their ancestral cellular interactions to build new genetic systems underlying developmental innovation and fostering organismal evolution. The PI will provide undergraduates, including minorities and first generation college students, with their first exposure to STEM research. The research and collaborations will guarantee that this functional genomics project will train rising scientists (graduate students and a postdoc) in cutting edge functional genomics technologies and data analysis.

The majority of domesticated TE genes known in a variety of organisms are derived from the transposase encoded by DNA transposons. The power of Drosophila genetics and genomics will be harnessed to begin the elucidation of the biological function of four likely independent domesticated transposase genes (DPLG1-4) and a set of proteins (MADFs) that are hypothesize to derive from the same TE superfamily. These are highly conserved in the Drosophila genus and are derived from the same superfamily of DNA transposons (PIF/Harbinger) .

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.