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

The sterlet sturgeon genome sequence and the mechanisms of segmental rediploidization.

Nat Ecol Evol. 2020 Mar 30;:

Authors: Du K, Stöck M, Kneitz S, Klopp C, Woltering JM, Adolfi MC, Feron R, Prokopov D, Makunin A, Kichigin I, Schmidt C, Fischer P, Kuhl H, Wuertz S, Gessner J, Kloas W, Cabau C, Iampietro C, Parrinello H, Tomlinson C, Journot L, Postlethwait JH, Braasch I, Trifonov V, Warren WC, Meyer A, Guiguen Y, Schartl M

Sturgeons seem to be frozen in time. The archaic characteristics of this ancient fish lineage place it in a key phylogenetic position at the base of the ~30,000 modern teleost fish species. Moreover, sturgeons are notoriously polyploid, providing unique opportunities to investigate the evolution of polyploid genomes. We assembled a high-quality chromosome-level reference genome for the sterlet, Acipenser ruthenus. Our analysis revealed a very low protein evolution rate that is at least as slow as in other deep branches of the vertebrate tree, such as that of the coelacanth. We uncovered a whole-genome duplication that occurred in the Jurassic, early in the evolution of the entire sturgeon lineage. Following this polyploidization, the rediploidization of the genome included the loss of whole chromosomes in a segmental deduplication process. While known adaptive processes helped conserve a high degree of structural and functional tetraploidy over more than 180 million years, the reduction of redundancy of the polyploid genome seems to have been remarkably random.

PMID: 32231327 [PubMed - as supplied by publisher]

Related Articles

Multiple independent chromosomal fusions accompanied the radiation of the Antarctic teleost genus Trematomus (Notothenioidei:Nototheniidae).

BMC Evol Biol. 2020 Mar 20;20(1):39

Authors: Auvinet J, Graça P, Dettai A, Amores A, Postlethwait JH, Detrich HW, Ozouf-Costaz C, Coriton O, Higuet D

BACKGROUND: Chromosomal rearrangements are thought to be an important driving force underlying lineage diversification, but their link to speciation continues to be debated. Antarctic teleost fish of the family Nototheniidae (Notothenioidei) diversified in a changing environmental context, which led to ecological, morphological, and genetic differentiation among populations. In addition, extensive chromosomal repatterning accompanied species divergence in several clades. The most striking karyotypic changes involved the recent species radiation (about 10 My) of the genus Trematomus, with chromosomal pair numbers ranging between 29 and 12. These dramatic reductions in chromosome number resulted mostly from large-scale chromosome fusions. Multiple centric and/or tandem fusions have been hypothesized in at least seven of the twelve recognized Trematomus species. To reconstruct their evolutionary history, we employed comparative cytogenomics (BAC-FISH and chromosome painting) to reveal patterns of interspecific chromosomal orthologies across several notothenioid clades.
RESULTS: We defined orthologous chromosomal segments of reference, termed Structural Units (SUs). SUs were identified in a total of 18 notothenioid species. We demonstrated for the first time that SUs were strongly conserved across every specimen examined, with chromosomal syntenies highlighting a paucity of intrachromosomal macro-rearrangements. Multiple independent fusions of these SUs were inferred in the Trematomus species, in contrast to the shared SU fusions in species of the sister lineage Notothenia.
CONCLUSIONS: The SU segments were defined units of chromosomal rearrangement in the entire family Nototheiidae, which diverged from the other notothenioid families 20 My ago. Some of the identified chromosomal syntenies within the SUs were even conserved in their closest relatives, the family Eleginopsidae. Comparing the timing of acquisition of the fusions in the closely related genera Notothenia and Trematomus of the nototheniid species family, we conclude that they exhibit distinct chromosomal evolutionary histories, which may be relevant to different speciation scenarios.

PMID: 32192426 [PubMed - in process]