Biology subjects

Muhl, V.

Publications and source records attributed to Muhl, V..

4 recordsLinked to original sources

bioRxiv2026

Long-term small effective population size, inbreeding, and a recessive lethal haplotype drive premature death in the endangered Devils Hole pupfish (Cyprinodon diabolis)

As anthropogenic habitat fragmentation and population decline accelerate globally, growing numbers of species face compounding demographic and genetic threats to long-term survival. Many populations are already forced to persist at chronically small sizes, yet the genomic and fitness consequences of this fate remain poorly understood. Here we leverage the demographic history of the Devils Hole pupfish to investigate how long-term small population size and recent bottlenecks have shaped genetic diversity, genetic load, inbreeding, and fitness through comparative population genomics, historical sequencing, and sampling embryos that died prematurely during development. We find that genetic diversity in Devils Hole pupfish is among the lowest recorded in the wild and that fixed load is high, consistent with thousands of generations of isolation at small population size. Even in the face of this low diversity and high fixed load, we show that inbreeding is still strongly associated with premature embryonic death, which affects up to 25% of offspring in the captive refuge and can be identified in advance based on a characteristic elongated heart tube and reduced heart rate. We discovered a recessive lethal haplotype segregating at [~]20% frequency that accounts for 50% of embryonic deaths and contains mutations in MIB1 and MMP16, genes associated with cardiomyopathy and atrial fibrillation. Our findings link genotype, phenotype, and fitness in an iconic endangered species to provide a rare comprehensive view into the evolutionary dynamics and consequences of long-term small effective population size, demonstrating that endangered species remain vulnerable to inbreeding depression despite extremely low genetic diversity.

evolutionary biology↗

bioRxiv2026

Diurnality reconfigures circadian network dynamics in the suprachiasmatic nucleus

Diurnal and nocturnal mammals occupy opposite temporal niches, but whether the suprachiasmatic nucleus (SCN), the central circadian pacemaker, follows the same intrinsic rules for timing adjustment and network coordination across species is unknown. Because SCN clock gene rhythms and population-level activity measurements look broadly similar across species, the prevailing interpretation in comparative studies has been that temporal niche differences are implemented upstream or downstream of the SCN. However, these coarse readouts do not test how clock resetting depends on circadian phase or how neuronal timing is coordinated across SCN space. Here, we combined long-duration ex vivo SCN recordings with optogenetic stimulation to compare SCN network dynamics in the nocturnal mouse (Mus musculus) and the diurnal four-striped grass mouse (Rhabdomys pumilio). Rhabdomys SCN molecular clock rhythms exhibited a longer intrinsic period and, under the same daily stimulation protocol, converged on a larger absolute phase angle relative to the stimulus. Molecular clock phase response curves differed in overall structure across circadian time between species, including pronounced early subjective day delays in Rhabdomys when Mus responses were minimal. Phase mapping of single-cell SCN calcium rhythms revealed species-specific spatial timing organization, with a graded dorsomedial-to-ventrolateral phase progression in Rhabdomys and a sharper transition in Mus. The Mus and Rhabdomys SCN can thus appear similar by coarse readouts yet diverge in phase-dependent molecular clock resetting and network timing organization. These results indicate that models placing temporal niche divergence solely outside the SCN are mechanistically incomplete.

neuroscience↗

bioRxiv2024

Tissue-specific transcriptomics uncovers novel craniofacial genes underlying jaw divergence in specialist pupfishes

The regulation of gene expression is one of the key evolutionary processes driving phenotypic divergence among species. Here, we investigate the tissue-specific gene expression of a non-model adaptive radiation of Cyprinodon pupfishes, characterized by their divergent dietary niches and exceptionally fast rates of craniofacial evolution. By comparing tissue-specific gene expression in the most morphologically divergent skeletal structure, the oral jaws, with the relatively morphologically conserved caudal tail region, we identified genes that were differentially expressed exclusively in the developing jaws of each of the three trophic specialists at hatching (8 dpf) and not in any other species. We then assessed their overlap (as transcriptionally-regulated genes) with adaptive regulatory variants identified in previous genomic studies. Our analysis identified pycr3 and atp8a1 as the most promising for craniofacial evolution in the scale-eaters, both genes with no known previous craniofacial function. We functionally confirmed the craniofacial expression of these genes by in situ mRNA hybridization chain reaction and demonstrated their species-specific expression in branchial and muscle tissues between sister species of this young radiation. Our work underscores the power of integrating tissue-specific transcriptomics with speciation genomics to identify novel craniofacial candidate genes controlling divergent morphogenesis in a natural evolutionary mutant system.

developmental biology↗

bioRxiv2023

Discovery of a new craniofacial gene influencing adaptive phenotypes in a non-model pupfish radiation

Understanding the genetic basis of novel adaptations in new species is a fundamental question in biology that also provides an opportunity to uncover new genes and regulatory networks with potential clinical relevance. Here we demonstrate a new role for galr2 in vertebrate craniofacial development using an adaptive radiation of trophic specialist pupfishes endemic to San Salvador Island in the Bahamas. We confirmed the loss of a putative Sry transcription factor binding site in the upstream region of galr2 in scale-eating pupfish and found significant spatial differences in galr2 expression among pupfish species in Meckels cartilage and premaxilla using in situ hybridization chain reaction (HCR). We then experimentally demonstrated a novel function for Galr2 in craniofacial development and jaw elongation by exposing embryos to drugs that inhibit Galr2 activity. Galr2-inhibition reduced Meckels cartilage length and increased chondrocyte density in both trophic specialists but not in the generalist genetic background. We propose a mechanism for jaw elongation in scale-eaters based on the reduced expression of galr2 due to the loss of a putative Sry binding site. Fewer Galr2 receptors in the scale-eater Meckels cartilage may result in their enlarged jaw lengths as adults by limiting opportunities for a postulated Galr2 agonist to bind to these receptors during development. Our findings illustrate the growing utility of linking candidate adaptive SNPs in non-model systems with highly divergent phenotypes to novel vertebrate gene functions.

developmental biology↗