Project description:Sexual reproduction is nearly universal among multicellular animals, but sex can be determined by cues including sex chromosomes, temperature, social status, and photoperiod. DMRT transcription factors are key regulators of sex in animals that use diverse sex-determining strategies. These proteins are related to the sexual regulators Doublesex (Dsx) and Male abnormal-3 (MAB-3) of insects and nematodes, respectively. DMRT proteins share the DM DNA binding domain, comprised of a unique intertwined double zinc-binding module flanked by a C-terminal recognition helix that binds to a pseudopalindromic target DNA. Despite the central role of DMRT proteins in metazoan sexual development, how they recognize target DNA sequences is poorly understood. Here we find that DMRT proteins employ multiple DNA binding modes due to surprising versatility in how specific base contacts are made. Human DMRT1 can bind as a dimer, trimer or tetramer, in each case using paired antiparallel recognition helices that together insert into a widened DNA major groove to make base-specific contacts. Insertion of two helices in a single major groove is, to our knowledge, a DNA binding interaction unique to DMRT proteins. High resolution in vivo DNA binding analysis (ChIP-Exo) indicates that multiple DNA binding modes also are used in the mouse testis. Finally, we show that mutations affecting amino acid residues crucial for DNA recognition are associated with sex reversal in flies and also, for the first time, with male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction that underlies much of metazoan sexual development.
Project description:This study tests the application of an innovative new method of sex determination utilizing enamel peptides on a sample of incompletely developed deciduous teeth, including those of perinates.
Project description:For many decades Indigenous people, including Native Americans and Aboriginal Australians, have fought for their return of their ancient people. By sequencing ten ancient nuclear genomes of Aboriginal Australians and 27 mitogenomes from ancient pre-European Aboriginal Australians (up to 1,540 yr BP) of known provenance we demonstrate the feasibility of successfully identifying the geographic origins of unprovenanced ancestral remains using genomic methods.
Project description:The assignment of biological sex to archaeological human skeletons is a fundamental requirement for the reconstruction of the human past. It is conventionally and routinely performed on adults using metric analysis and morphological traits arising from postpubertal sexual dimorphism. A maximum accuracy of ?95% is possible if both the cranium and os coxae are present and intact, but this is seldom achievable for all skeletons. Furthermore, for infants and juveniles, there are no reliable morphological methods for sex determination without resorting to DNA analysis, which requires good DNA survival and is time-consuming. Consequently, sex determination of juvenile remains is rarely undertaken, and a dependable and expedient method that can correctly assign biological sex to human remains of any age is highly desirable. Here we present a method for sex determination of human remains by means of a minimally destructive surface acid etching of tooth enamel and subsequent identification of sex chromosome-linked isoforms of amelogenin, an enamel-forming protein, by nanoflow liquid chromatography mass spectrometry. Tooth enamel is the hardest tissue in the human body and survives burial exceptionally well, even when the rest of the skeleton or DNA in the organic fraction has decayed. Our method can reliably determine the biological sex of humans of any age using a body tissue that is difficult to cross-contaminate and is most likely to survive. The application of this method will make sex determination of adults and, for the first time, juveniles a reliable and routine activity in future bioarcheological and medico-legal science contexts.
Project description:Morphological identification of ancient bone is often problematic due to heavy fragmentation that generally influences zooarchaeological assemblages. Fish bones are more taphonomically sensitive than those of other vertebrates as they are typically smaller and less biomineralised. Thus, taxonomic identification based on the preservation of morphological features is often extremely limited and can reduce or eliminate the usefulness of an assemblage for inferring taxon information. Currently, one of the most time- and cost-efficient methods of achieving faunal identity from ancient bone is by the collagen fingerprinting technique known as ZooMS (Zooarchaeology by Mass Spectrometry). ZooMS harnesses the potential of preserved collagen, which is the most dominant and time-stable protein in bone. In this research, ZooMS is applied to ancient Baltic region fish assemblages that are between 500 and 6000 years old in order to define species identity and construct assemblage compositions. Alongside inferences into environmental and biological shifts from the Neolithic era to present day in the Baltic region, we demonstrate for the first time the ability to distinguish between recently diverged members of the Salmo (salmon) and Scophthalmus (turbot) genera. ZooMS analysis highlights 7% of the collagen-containing assemblage as having been morphologically identified incorrectly and has facilitated taxonomic refinement of a further 28% of samples, including some of the morphologically indeterminate bone fragments. This research emphasises the great potential of ZooMS in identifying ichthyoarchaeological bone remains to species-level, and provides a case for the use of collagen fingerprinting in contributing to baseline fisheries and ecological data, to inform modern management.
Project description:DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA-binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds a pseudopalindromic target DNA. Here we show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to use multiple DNA binding modes (tetramer, trimer and dimer). Chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) indicates that multiple DNA binding modes also are used in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and with male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction underlying much of metazoan sexual development.