John Postlethwait

Professor, Department of Biology
Member, ION

Ph.D. Case Western Reserve
B.S. Stanford Univeristy

 

Research Interests: Genetic regulation of animal development including development of the nervous system, the mechanisms of sex determination, the origin of novel morphologies in evolution and the evolution of the vertebrate genome.

Overview: Our laboratory is interested in the genetic, genomic, and evolutionary principles that guide animal development. We investigate several aspects of this main problem: 

Genome Duplication: The evolution of gene functions in development after genome duplication, focusing on skeletal development.

Fanconi anemia: A small molecule screen for compounds to rescue zebrafish Fanconi Anemia mutants as a way to identify potential therapeutics for human FA patients and to understand disease mechanisms.

MicroRNAs: The roles of microRNAs in embryonic (especially skeletal) development, including evolving miRNA functions after genome duplication.

Icefish: The genetic basis for the evolution of osteopenia or osteoporosis in Antarctic icefish.

Sex determinaion:The developmental genetic basis for sex determination in zebrafish.

Speciation: The roles of genome duplication in lineage divergence, focusing on the evolution of cis and trans acting regulation in the radiation of the danio lineage, including zebrafish, and on variation among populations of stickleback.

Oikopleura: Retaining a chordate body plan as an adult, the larvacean urochordate Oikopleura dioica represents the sister lineage to the vertebrates, diverging before the R1 and R2 rounds of genome duplication that led to the origin of vertebrate innovations.

Perchlorate toxicity and sex determination: Perchlorate is a pervasive environmental contaminant that can cause partial sex reversal in stickleback. We are investigating the hypotheses that perchlorate alters sex development through the thyroid or a non-thyroidal mechanism.

Drosophila developmental genetics: Work on Drosophila homeotic mutants, pattern formation, and ovary development.

RECENT PUBLICATIONS

Endocrine disruption and differential gene expression in sentinel fish on St. Lawrence Island, Alaska: Health implications for indigenous residents.

Environ Pollut. 2017 Nov 25;234:279-287

Authors: von Hippel FA, Miller PK, Carpenter DO, Dillon D, Smayda L, Katsiadaki I, Titus TA, Batzel P, Postlethwait JH, Buck CL

Abstract
People living a subsistence lifestyle in the Arctic are highly exposed to persistent organic pollutants, including polychlorinated biphenyls (PCBs). Formerly Used Defense (FUD) sites are point sources of PCB pollution; the Arctic contains thousands of FUD sites, many co-located with indigenous villages. We investigated PCB profiles and biological effects in freshwater fish (Alaska blackfish [Dallia pectoralis] and ninespine stickleback [Pungitius pungitius]) living upstream and downstream of the Northeast Cape FUD site on St. Lawrence Island in the Bering Sea. Despite extensive site remediation, fish remained contaminated with PCBs. Vitellogenin concentrations in males indicated exposure to estrogenic contaminants, and some fish were hypothyroid. Downstream fish showed altered DNA methylation in gonads and altered gene expression related to DNA replication, response to DNA damage, and cell signaling. This study demonstrates that, even after site remediation, contaminants from Cold War FUD sites in remote regions of the Arctic remain a potential health threat to local residents - in this case, Yupik people who had no influence over site selection and use by the United States military.

PMID: 29182972 [PubMed - as supplied by publisher]

The Spotted Gar: Genomic Journeys into a Lost World.

J Exp Zool B Mol Dev Evol. 2017 Nov;328(7):593-595

Authors: Braasch I, Postlethwait JH

PMID: 29059506 [PubMed - in process]

Evolution of gene expression after whole-genome duplication: New insights from the spotted gar genome.

J Exp Zool B Mol Dev Evol. 2017 Sep 25;:

Authors: Pasquier J, Braasch I, Batzel P, Cabau C, Montfort J, Nguyen T, Jouanno E, Berthelot C, Klopp C, Journot L, Postlethwait JH, Guiguen Y, Bobe J

Abstract
Whole-genome duplications (WGDs) are important evolutionary events. Our understanding of underlying mechanisms, including the evolution of duplicated genes after WGD, however, remains incomplete. Teleost fish experienced a common WGD (teleost-specific genome duplication, or TGD) followed by a dramatic adaptive radiation leading to more than half of all vertebrate species. The analysis of gene expression patterns following TGD at the genome level has been limited by the lack of suitable genomic resources. The recent concomitant release of the genome sequence of spotted gar (a representative of holosteans, the closest-related lineage of teleosts that lacks the TGD) and the tissue-specific gene expression repertoires of over 20 holostean and teleostean fish species, including spotted gar, zebrafish, and medaka (the PhyloFish project), offers a unique opportunity to study the evolution of gene expression following TGD in teleosts. We show that most TGD duplicates gained their current status (loss of one duplicate gene or retention of both duplicates) relatively rapidly after TGD (i.e., prior to the divergence of medaka and zebrafish lineages). The loss of one duplicate is the most common fate after TGD with a probability of approximately 80%. In addition, the fate of duplicate genes after TGD, including subfunctionalization, neofunctionalization, or retention of two "similar" copies occurred not only before but also after the divergence of species tested, in consistency with a role of the TGD in speciation and/or evolution of gene function. Finally, we report novel cases of TGD ohnolog subfunctionalization and neofunctionalization that further illustrate the importance of these processes.

PMID: 28944589 [PubMed - as supplied by publisher]