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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM071813-06
Application #
8187321
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2005-05-01
Project End
2015-04-30
Budget Start
2011-09-01
Budget End
2012-04-30
Support Year
6
Fiscal Year
2011
Total Cost
$167,127
Indirect Cost
Name
University of Texas Arlington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
064234610
City
Arlington
State
TX
Country
United States
Zip Code
76019
Casola, Claudio; Betrán, Esther (2017) The Genomic Impact of Gene Retrocopies: What Have We Learned from Comparative Genomics, Population Genomics, and Transcriptomic Analyses? Genome Biol Evol 9:1351-1373
Eslamieh, Mohammadmehdi; Williford, Anna; Betrán, Esther (2017) Few Nuclear-Encoded Mitochondrial Gene Duplicates Contribute to Male Germline-Specific Functions in Humans. Genome Biol Evol 9:2782-2790
Jangam, Diwash; Feschotte, Cédric; Betrán, Esther (2017) Transposable Element Domestication As an Adaptation to Evolutionary Conflicts. Trends Genet 33:817-831
Gallach, Miguel; Betrán, Esther (2016) Dosage Compensation and the Distribution of Sex-Biased Gene Expression in Drosophila: Considerations and Genomic Constraints. J Mol Evol 82:199-206
Betrán, Esther (2015) The ""life histories"" of genes. J Mol Evol 80:186-8
Guillén, Yolanda; Rius, Núria; Delprat, Alejandra et al. (2015) Genomics of ecological adaptation in cactophilic Drosophila. Genome Biol Evol 7:349-66
Sorourian, Mehran; Kunte, Mansi M; Domingues, Susana et al. (2014) Relocation facilitates the acquisition of short cis-regulatory regions that drive the expression of retrogenes during spermatogenesis in Drosophila. Mol Biol Evol 31:2170-80
Calvete, Oriol; González, Josefa; Betrán, Esther et al. (2012) Segmental duplication, microinversion, and gene loss associated with a complex inversion breakpoint region in Drosophila. Mol Biol Evol 29:1875-89
Gallach, Miguel; Domingues, Susana; Betrán, Esther (2011) Gene duplication and the genome distribution of sex-biased genes. Int J Evol Biol 2011:989438
Hosken, David J (2011) Gene duplication might not resolve intralocus sexual conflict. Trends Ecol Evol 26:556-7; author reply 558-9

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