Meiklejohn Lab

Research Interests

Current research in the Meiklejohn lab uses functional, evolutionary, and comparative genetics and genomics to understand the evolution and regulation of sex chromosomes and spermatogenesis, using the fruit fly Drosophila as a model.

Sex chromosomes are subject to distinct evolutionary forces, owing to their sex-linkage, hemizygosity, and the lack of genetic exchange. These unique features influence gene sequence evolution, gene regulation, and endow sex chromosomes with a special role in the formation of new species - sex chromosomes are hotspots for incompatibilities that cause sterility in interspecies hybrids. We use genetic, molecular, developmental, and comparative approaches to address the following questions:

  1. What is the genetic and molecular basis for X-linked factors that cause sterility in interspecific hybrid males?
  2. What is the genetic and molecular basis for X-chromosome regulation in the Drosophila male germline?
  3. What are the evolutionary forces that drive both X-chromosome specific regulatory phenomena and the enrichment of reproductive isolating factors on this chromosome?

X-linked hybrid male sterility factors

Speciation can result from the evolution of reproductive isolation in the form of postzygotic incompatibilities – interactions between alleles from two species that render hybrids inviable or sterile. In animal taxa with heteromorphic (XY or ZW) sex chromosomes, the earliest hybrid incompatibilities to accumulate cause sterility in the heterogametic sex (Haldane's Rule). At least in part, Haldane’s Rule results from an enrichment of sterility-causing incompatibilities on the X chromosome (the large X-effect). Thus, in XY taxa, both the X chromosome and the rapid evolution of spermatogenesis have been implicated as key components of the earliest postzygotic incompatibilities. However, why the X chromosome has a unique role in speciation, across a wide range of taxa, is unclear.

To identify and characterize hybrid male sterility factors we have generated a genetic map of X-linked hybrid male sterility between Drosophila simulans and D. mauritiana. At least seven distinct regions on the D. mauritiana X chromosome are sufficient forcomplete male sterility in combination with the Y and autosomes from D. simulans. We currently pursuing experiments to fine-map, clone and validate two X-linked HMS factors. We are also studying spermatogenesis in sterile hybrid males to determine the developmental mechanisms whereby these genes disrupt spermatogenesis to cause sterility.

X-chromosome regulation in the Drosophila male germline

We are currently studying regulation of the X chromosome in D. melanogaster testes. Our previous research has revealed that, unlike in male somatic cells, the X chromosome is not dosage compensated in the Drosophila male germline; and unlike mammals and nematodes, Drosophila shows no evidence of meiotic X chromosome inactivation. Despite the absence of meiotic sex chromosome inactivation, our previous work indicates that the D. melanogaster X chromosome is subject to a different form of regulatory suppression during spermatogenesis, and that it is largely compensated by the evolution of X-linked cis-regulatory sequences. We are currently pursuing experiments to further characterize spermatogenic X-suppression in Drosophila, using genetic, transgenic, and transcriptomic approaches to dissect the roles of the Y chromosome and heterochromatin in X-suppression.

Genomic parasites and the integrative biology of spermatogenesis

Across animals, the genetic control of spermatogenesis is characterized by rapid evolutionary turnover and unique genomic architecture and gene regulation. My hypothesis is that these unusual patterns associated with sex chromosomes and gametogenesis derive from a single source - genomic parasites acting in their selfish interests to increase in frequency at the expense of their host organism. Studying the genetic basis of germline and sex-chromosome specific regulation and hybrid male sterility provides a test of whether genes involved in these processes are part of this conflict between parasites and hosts.

Functional and evolutionary genetics and genomics

Additional research in the Meiklejohn lab includes investigations into a role for mitochondrial-nuclear interactions and temperature-dependent male sterility in Drosophila; characterization of genetic and molecular mechanisms of triplo-lethality associated with the Triplo-lethal locus in Drosophila; using Drosophila strains infected with common viruses to establish an empirical system to investigate epidemiological models; and generation of “platinum” high-quality genome assemblies and annotations for the Drosophila simulans species group. In all of these projects, we seek to uncover the evolutionary and genetic mechanisms that underlie important biological phenomenon and shape genome regulation and evolution.