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.


Related Articles

RADSex: a computational workflow to study sex determination using Restriction Site-Associated DNA Sequencing data.

Mol Ecol Resour. 2021 Feb 16;:

Authors: Feron R, Pan Q, Wen M, Imarazene B, Jouanno E, Anderson J, Herpin A, Journot L, Parrinello H, Klopp C, Kottler VA, Roco AS, Du K, Kneitz S, Adolfi M, Wilson CA, McCluskey B, Amores A, Desvignes T, Goetz FW, Takanashi A, Kawaguchi M, Detrich HW, Oliveira M, Nobrega R, Sakamoto T, Nakamoto M, Wargelius A, Karlsen Ø, Wang Z, Stöck M, Waterhouse RM, Braasch I, Postlethwait JH, Schartl M, Guiguen Y

The study of sex determination and sex chromosome organisation in non-model species has long been technically challenging, but new sequencing methodologies now enable precise and high-throughput identification of sex-specific genomic sequences. In particular, Restriction Site-Associated DNA Sequencing (RAD-Seq) is being extensively applied to explore sex determination systems in many plant and animal species. However, software specifically designed to search for and visualize sex-biased markers using RAD-Seq data is lacking. Here, we present RADSex, a computational analysis workflow designed to study the genetic basis of sex determination using RAD-Seq data. RADSex is simple to use, requires few computational resources, makes no prior assumptions about the type of sex-determination system or structure of the sex locus, and offers convenient visualization through a dedicated R package. To demonstrate the functionality of RADSex, we re-analyzed a published dataset of Japanese medaka, Oryzias latipes, where we uncovered a previously unknown Y chromosome polymorphism. We then used RADSex to analyze new RAD-Seq datasets from 15 fish species spanning multiple taxonomic orders. We identified the sex determination system and sex-specific markers in six of these species, five of which had no known sex-markers prior to this study. We show that RADSex greatly facilitates the study of sex determination systems in non-model species thanks to its speed of analyses, low resource usage, ease of application, and visualization options. Furthermore, our analysis of new datasets from 15 species provides new insights on sex determination in fish.

PMID: 33590960 [PubMed - as supplied by publisher]

Related Articles

The rise and fall of the ancient northern pike master sex determining gene.

Elife. 2021 Jan 28;10:

Authors: Pan Q, Feron R, Jouanno E, Darras H, Herpin A, Koop B, Rondeau E, Goetz FW, Larson WA, Bernatchez L, Tringali M, Curran SS, Saillant E, Denys GP, von Hippel FA, Chen S, López JA, Verreycken H, Ocalewicz K, Guyomard R, Eche C, Lluch J, Roques C, Hu H, Tabor R, DeHaan P, Nichols KM, Journot L, Parrinello H, Klopp C, Interesova EA, Trifonov V, Schartl M, Postlethwait JH, Guiguen Y

The understanding of the evolution of variable sex determination mechanisms across taxa requires comparative studies among closely related species. Following the fate of a known master sex-determining gene, we traced the evolution of sex determination in an entire teleost order (Esociformes). We discovered that the northern pike (Esox lucius) master sex-determining gene originated from a 65 to 90 million-year-old gene duplication event and that it remained sex-linked on undifferentiated sex chromosomes for at least 56 million years in multiple species. We identified several independent species- or population-specific sex determination transitions, including a recent loss of a Y-chromosome. These findings highlight the diversity of evolutionary fates of master sex-determining genes and the importance of population demographic history in sex determination studies. We hypothesize that occasional sex reversals and genetic bottlenecks provide a non-adaptive explanation for sex determination transitions.

PMID: 33506762 [PubMed - as supplied by publisher]

Related Articles

The Developmental and Genetic Architecture of the Sexually Selected Male Ornament of Swordtails.

Curr Biol. 2020 Dec 02;:

Authors: Schartl M, Kneitz S, Ormanns J, Schmidt C, Anderson JL, Amores A, Catchen J, Wilson C, Geiger D, Du K, Garcia-Olazábal M, Sudaram S, Winkler C, Hedrich R, Warren WC, Walter R, Meyer A, Postlethwait JH

Sexual selection results in sex-specific characters like the conspicuously pigmented extension of the ventral tip of the caudal fin-the "sword"-in males of several species of Xiphophorus fishes. To uncover the genetic architecture underlying sword formation and to identify genes that are associated with its development, we characterized the sword transcriptional profile and combined it with genetic mapping approaches. Results showed that the male ornament of swordtails develops from a sexually non-dimorphic prepattern of transcription factors in the caudal fin. Among genes that constitute the exclusive sword transcriptome and are located in the genomic region associated with this trait we identify the potassium channel, Kcnh8, as a sword development gene. In addition to its neural function kcnh8 performs a known role in fin growth. These findings indicate that during evolution of swordtails a brain gene has been co-opted for an additional novel function in establishing a male ornament.

PMID: 33275891 [PubMed - as supplied by publisher]