Biology subjects

McCann, J.

Publications and source records attributed to McCann, J..

5 recordsLinked to original sources

bioRxiv2025

A Y-linked duplication of anti-Mullerian hormone is the sex determination gene in threespine stickleback

Many taxa have independently evolved genetic sex determination where a single gene located on a sex chromosome controls gonadal differentiation. The gene anti-Mullerian hormone (amh) has convergently evolved as a sex determination gene in numerous vertebrate species, but how this gene has repeatedly evolved this novel function is not well understood. In the threespine stickleback (Gasterosteus aculeatus), amh was duplicated onto the Y chromosome (amhy) [~]22 million years ago. To determine whether amhy is the primary sex determination gene, we used CRISPR/Cas9 and transgenesis to show that amhy is necessary and sufficient for male sex determination, consistent with the function of a primary sex determination gene. We find that amhy contributes to a higher total dosage of amh early in development and likely contributes to differential germ cell proliferation key to sex determination. The creation of sex reversed lines also allowed us to investigate the genetic basis of secondary sex characteristics. Threespine stickleback have striking differences in behavior and morphology between sexes. Here we show one of the classic traits important for reproductive success, blue male nuptial coloration, is controlled by both sex-linked genetic factors as well as hormonal factors independent of sex chromosome genotype. This research establishes stickleback as a model to investigate how amh regulates gonadal development and how this gene repeatedly evolves novel function in sex determination. Analogous to the "four core genotypes" model in house mice, sex-reversed threespine stickleback offer a new vertebrate model for investigating the separate contributions of gonadal sex and sex chromosomes to sexual dimorphism. Author SummaryMany species have evolved sex chromosomes like the XY system found in humans and other mammals. While sex chromosomes can contain hundreds of genes, a single sex determination gene found on the sex chromosomes controls whether the gonad develops into an ovary or testis. Many different sex determination genes have been identified across species, but we still have much to learn about how different sex determination genes control the same process of sex determination. Here, we show that an extra copy of the gene anti-Mullerian hormone on the Y chromosome of threespine stickleback fish is the sex determination gene responsible for initiating testis development. By manipulating this sex determination gene, we are now able to generate male and female stickleback with either XX or XY sex chromosome genotypes. This allows us to investigate the role of sex chromosomes in fitness and development outside of sex determination which is not possible in many models. Surprisingly, we find that the Y chromosome is not necessary for male fertility in stickleback. We also show that a key secondary sex characteristic, male mating color, is controlled both by hormones produced by the gonad as well as independent genetic factors on the sex chromosomes.

genetics↗

bioRxiv2023

CNC Knitting Micro-Resolution Mosquito Bite Blocking Textiles

Mosquitoes and other biting arthropods transmit diseases worldwide, causing over 700,000 deaths each year, and costing about 3 billion annually for Aedes species alone. These insects also pose a significant threat to agricultural animals. While clothing could provide a simple solution to vector-borne diseases, modern textiles do not effectively block mosquito bites. To address this issue, we have designed three micro-resolution knitted structures, with five adjustable parameters, that can block bites. These designs were integrated into a computer numerical control knitting robot for mass production of bite-blocking garments with minimal human labor. We then quantified the comfort of blocking garments. Our knits enable individuals to protect themselves from insects amidst their day-to-day activities without impacting the environment. One Sentence SummaryWe create micro-resolution mosquito bite blocking knits produced by robotic manufacturing to protect humans against vector-borne disease.

bioengineering↗

bioRxiv2021

R-loop homeostasis and cancer mutagenesis promoted by the DNA cytosine deaminase APOBEC3B

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here, APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in human cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts overexpressed genes and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B mediates R-loop homeostasis and contributes to R-loop mutagenesis in cancer. HighlightsO_LIUnbiased proteomics link antiviral APOBEC3B to R-loop regulation C_LIO_LISystematic alterations of APOBEC3B levels trigger corresponding changes in R-loops C_LIO_LIAPOBEC3B binds R-loops in living cells and in vitro C_LIO_LIBioinformatics analyses support an R-loop deamination and mutation model C_LI

cancer biology↗

bioRxiv2018

Polyomavirus T-Antigen Induces APOBEC3B Expression using a LXCXE-Dependent and TP53-Independent Mechanism

APOBEC3B is a single-stranded DNA cytosine deaminase with beneficial innate antiviral functions. However, misregulated APOBEC3B can also be detrimental by inflicting APOBEC signature C-to-T and C-to-G mutations in genomic DNA of multiple cancer types. Polyomaviruses and papillomaviruses use dominant oncoproteins to induce APOBEC3B overexpression, perhaps to their own benefit, but little is known about the cellular mechanisms hijacked by these viruses to do so. Here we investigate the molecular mechanism of APOBEC3B upregulation by the polyomavirus large T-antigen. First, truncated T-antigen (truncT) is sufficient for APOBEC3B upregulation and the RB interacting motif (LXCXE), but not the TP53 inhibition domain, is required. Second, upregulated APOBEC3B is strongly nuclear and partially localized to virus replication centers. Third, genetic knockdown of RB1 alone or in combination with RBL1 and/or RBL2 is insufficient to suppress truncT-mediated induction of APOBEC3B. Fourth, CDK4/6 inhibition by palbociclib is also insufficient to suppress truncT-mediated induction of APOBEC3B. Fifth, global gene expression analyses in a wide range of human cancers show significant associations between expression of APOBEC3B and other genes known to be regulated by the RB/E2F axis. These experiments combine to implicate the RB/E2F axis in promoting APOBEC3B transcription, yet they also suggest that the polyomavirus RB binding motif has in addition to RB inactivation at least one additional function for triggering APOBEC3B upregulation in virus-infected cells.\n\nIMPORTANCEThe APOBEC3B DNA cytosine deaminase is overexpresssed in many different cancers and correlated with elevated frequencies of C-to-T and C-to-G mutations in 5-TC motifs, oncogene activation, acquired drug resistance, and poor clinical outcomes. The mechanisms responsible for APOBEC3B overexpression are not fully understood. Here, we show that the polyomavirus truncated T-antigen (truncT) triggers APOBEC3B overexpression through its RB-interacting motif, LXCXE, which in turn likely enables one or more E2F family transcription factors to promote APOBEC3B expression. This work strengthens the mechanistic linkage between active cell cycling, APOBEC3B overexpression, and cancer mutagenesis. Although this mechanism damages cellular genomes, viruses may leverage it to promote evolution, immune escape, and pathogenesis. The cellular portion of the mechanism may also be relevant to non-viral cancers, where genetic mechanisms often activate the RB/E2F axis and APOBEC3B mutagenesis contributes to tumor evolution.

microbiology↗

bioRxiv2017

Bird interactions with drones, from individuals to large colonies

Drones are rapidly becoming a key part of the toolkit for a range of scientific disciplines, as well as a range of management and commercial applications. This presents a number of challenges in context of how drone use might impact nearby wildlife. Interactions between birds and drones naturally come to mind, since they share the airspace. This paper details initial findings on the interactions between drones and birds for a range of waterbird, passerine and raptor species, across of a range of scientific applications and natural environments. The primary aims of this paper are to provide guidance for those planning or undertaking drone monitoring exercises, as well as provide direction for future research into safe and effective monitoring with drones. Our study sites we all located within Australia and spanned a range of arid, semi-arid, dunefield, floodplain, wetland, woodland, forest, coastal heath and urban environments. We particularly focus on behavioral changes towards drones during breeding season, interactions with raptors, and effects on nesting birds in large colonies - three areas yet to be explored in published literature. In over 70 hours of flight, there were no incidents with birds. Although some aggressive behavior was encountered from solitary breeding birds. Several large breeding bird colonies were surveyed, and included in our observations is monitoring and counting of nests in a colony of over 200,000 Straw-necked Ibis, the largest drone-based bird monitoring exercise to date. In addition to providing observations of interactions with specific bird species, we recommend procedures for flight planning, safe flying and avoidance. This paper also provides a basis for a number of critical and emerging areas of research into bird-drone interactions, most notably, territorial breeding birds, safety around large raptors, and the effect of drones on the behaviour of birds in large breeding colonies.

ecology↗