Doris Bachtrog



Bachtrog Lab

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Research Overview

My main research interest is in the evolutionary significance of sex and recombination and its implications for the mode and tempo of genome evolution. Questions of interest to me include: Why is recombination so prevalent in eukaryotes? Why do non-recombining parts of the genome in sexual species, like the Y chromosome, degenerate? How do patterns of genome evolution and genome-wide expression-levels respond to changes in genome architecture and recombination rate? How does dosage compensation evolve?

Most of my work involves using Drosophila as a model. With the forthcoming completion of the entire genome sequence of 12 different Drosophila species, combined with the wealth of genetic tools available, Drosophila provides an ideal system to answer evolutionary genomics questions using a comparative framework. I use several different approaches in my research, combining molecular and computational genomics techniques, comparative and functional genomics approaches, theoretical modeling and experimental tests. Current research focuses on the following areas:

The causes of Y chromosome degeneration.
It is generally believed that the advantage of sex lies in the associated process of genetic recombination during meiosis, which constitutes the main difference between sexual and asexual reproduction. Asexual species of eukaryotes seem to go extinct at a higher rate than their sexual relatives. Likewise, non-recombining parts of the genome in sexual species are prone to degeneration: X and Y chromosomes are derived from a pair of ordinary autosomes, and the lack of recombination on the Y chromosome has resulted in its degeneration. The non-recombining portion of Y chromosomes is characterized by a paucity of active genes and an abundance of repetitive sequences. I am using comparative genomics approaches, population genetics and molecular genetic approaches to study the forces responsible for Y chromosome degeneration in Drosophila, using three model species: D. miranda, D. albomicans and D. athabasca. These species all have Y chromosomes that were formed very recently on an evolutionary time scale, allowing us to study the process of Y chromosome degeneration in action.

The evolution of gene expression and dosage compensation.
The degeneration of the Y chromosome creates the problem of reduced gene-dosage of X-linked genes in males, resulting in the evolution of dosage-compensation mechanisms. Dramatically different dosage-compensation mechanisms have evolved in different organisms: Mammals inactivate one of their two X chromosomes in females, XX hermaphrodite C. elegans effectively halve the expression from each X, and male Drosophila increase the transcription of their single X approximately twofold. Large parts of the neo-Y chromosome in D. miranda show various signs of degeneration, and some parts of the neo-X already recruit the molecular machinery necessary for dosage compensation. Using a library of tools from comparative genomics, population genetics to gene expression studies, I investigate how gene expression patterns evolve on these newly formed sex chromosomes, and, in particular, the evolution of dosage compensation.

Adaptation in asexual genomes.
All natural populations have to adapt to new environments. Despite its importance, the process of adaptation is far from being understood. I am carrying out theoretical and experimental evolution studies, to investigate the process of adaptation in asexuals. On a non-recombining genome, like in asexuals or the Y chromosome, deleterious mutations can considerably reduce the rate of fixation of advantageous alleles. In collaboration with Dr. I. Gordo (Institute Gulbenkian of Science, Portugal), I am performing theoretical investigations and simulation studies of the population genetics of adaptation in asexual populations. I am testing predictions of these models using an experimental evolution approach.

Mammals with clonal chromosomes.
In most mammals, females have two X chromosomes, and males have an X and a Y chromosome (XX vs. XY). However, some rodents have very unusual sex chromosome systems. In the creeping vole, Microtus oregoni, males are XY and females are X0 while in the mole vole, Ellobius lutescens, both males and females are X0. Thus, the X chromosome in these species is completely sheltered from recombination. Using population genetics and molecular evolution approaches, I am investigating the evolutionary origin of these bizarre sex chromosome systems.

Y chromosome degeneration; Mammals with bizarre sex chromosomes; Evolution of
				dosage compensation

Selected publications

Bachtrog, D. (2004). Evidence that positive selection drives Y-chromosome degeneration in Drosophila miranda. Nature Genetics 36(5): 518-522.

Bachtrog, D. & I. Gordo. (2004). Adaptive evolution of asexual populations under Muller's ratchet. Evolution 58(7):, 1403-1413.

Bachtrog, D. (2003). Protein evolution and codon usage bias on the neo-sex chromosomes of Drosophila miranda. Genetics, 165: 1221-1232.

Bachtrog, D. (2003). Adaptation shapes patterns of genome evolution on sexual and asexual chromosomes in Drosophila. Nature Genetics, 34 (2): 215-219.

Bachtrog, D. (2003). Accumulation of spock and worf, two novel retrotransposons, on the neo-Y chromosome of Drosophila miranda. Molecular Biology and Evolution, 20 (2): 173-181.

Bachtrog, D. & B. Charlesworth (2002). Reduced adaptation on a non-recombining neo-Y chromosome. Nature, 416 (6878): 323-326.

Bachtrog, D. & B. Charlesworth (2001). Towards a complete sequence of the human Y chromosome. Genome Biology, 2 (5):1016.1-1016.5.

Bachtrog, D. & B. Charlesworth (2000). Reduced levels of microsatellite variability on the neo-Y chromosome of Drosophila miranda. Current Biology, 10 (17): 1025-1031.