Clinical, genetic, epidemiologic, evolutionary, and functional delineation of TSPEAR-related autosomal recessive ectodermal dysplasia 14.

TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the ß-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara -/-;tspearb -/- double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.

Episodes of gene flow and selection during the evolutionary history of domesticated barley.

BACKGROUND: Barley is one of the founder crops of Neolithic agriculture and is among the most-grown cereals today. The only trait that universally differentiates the cultivated and wild subspecies is 'non-brittleness' of the rachis (the stem of the inflorescence), which facilitates harvesting of the crop. Other phenotypic differences appear to result from facultative or regional selective pressures. The population structure resulting from these regional events has been interpreted as evidence for multiple domestications or a mosaic ancestry involving genetic interaction between multiple wild or proto-domesticated lineages. However, each of the three mutations that confer non-brittleness originated in the western Fertile Crescent, arguing against multiregional origins for the crop. RESULTS: We examined exome data for 310 wild, cultivated and hybrid/feral barley accessions and showed that cultivated barley is structured into six genetically-defined groups that display admixture, resulting at least in part from two or more significant passages of gene flow with distinct wild populations. The six groups are descended from a single founding population that emerged in the western Fertile Crescent. Only a few loci were universally targeted by selection, the identity of these suggesting that changes in seedling emergence and pathogen resistance could represent crucial domestication switches. Subsequent selection operated on a regional basis and strongly contributed to differentiation of the genetic groups. CONCLUSIONS: Identification of genetically-defined groups provides clarity to our understanding of the population history of cultivated barley. Inference of population splits and mixtures together with analysis of selection sweeps indicate descent from a single founding population, which emerged in the western Fertile Crescent. This founding population underwent relatively little genetic selection, those changes that did occur affecting traits involved in seedling emergence and pathogen resistance, indicating that these phenotypes should be considered as 'domestication traits'. During its expansion out of the western Fertile Crescent, the crop underwent regional episodes of gene flow and selection, giving rise to a modern genetic signature that has been interpreted as evidence for multiple domestications, but which we show can be rationalized with a single origin.

The first reported case of the rare mitochondrial haplotype H4a1 in ancient Egypt.

Takabuti, was a female who lived in ancient Egypt during the 25th Dynasty, c.660 BCE. Her mummified remains were brought to Belfast, Northern Ireland, in 1834 and are currently displayed in the Ulster Museum. To gain insight into Takabuti's ancestry, we used deep sampling of vertebral bone, under X-ray control, to obtain non-contaminated bone tissue from which we extracted ancient DNA (aDNA) using established protocols. We targeted the maternally inherited mitochondrial DNA (mtDNA), known to be highly informative for human ancestry, and identified 38 single nucleotide variants using next generation sequencing. The specific combination of these SNVs suggests that Takabuti belonged to mitochondrial haplogroup H4a1. Neither H4 nor H4a1 have been reported in ancient Egyptian samples, prior to this study. The modern distribution of H4a1 is rare and sporadic and has been identified in areas including the Canary Islands, southern Iberia and the Lebanon. H4a1 has also been reported in ancient samples from Bell Beaker and Unetice contexts in Germany, as well as Bronze Age Bulgaria. We believe that this is an important finding because first, it adds to the depth of knowledge about the distribution of the H4a1 haplogroup in existing mtDNA, thus creating a baseline for future occurrences of this haplogroup in ancient Egyptian remains. Second, it is of great importance for archaeological sciences, since a predominantly European haplogroup has been identified in an Egyptian individual in Southern Egypt, prior to the Roman and Greek influx (332BCE).

Preserved collagen reveals species identity in archaeological marine turtle bones from Caribbean and Florida sites.

Advancements in molecular science are continually improving our knowledge of marine turtle biology and evolution. However, there are still considerable gaps in our understanding, such as past marine turtle distributions, which can benefit from advanced zooarchaeological analyses. Here, we apply collagen fingerprinting to 130 archaeological marine turtle bone samples up to approximately 2500 years old from the Caribbean and Florida's Gulf Coast for faunal identification, finding the vast majority of samples (88%) to contain preserved collagen despite deposition in the tropics. All samples can be identified to species-level with the exception of the Kemp's ridley (Lepidochelys kempii) and olive ridley (L. olivacea) turtles, which can be separated to genus level, having diverged from one another only approximately 5 Ma. Additionally, we identify a single homologous peptide that allows the separation of archaeological green turtle samples, Chelonia spp., into two distinct groups, which potentially signifies a difference in genetic stock. The majority of the archaeological samples are identified as green turtle (Chelonia spp.; 63%), with hawksbill (Eretmochelys imbricata; 17%) and ridley turtles (Lepidochelys spp.; 3%) making up smaller proportions of the assemblage. There were no molecular identifications of the loggerhead turtle (Caretta caretta) in the assemblage despite 9% of the samples being morphologically identified as such, highlighting the difficulties in relying on morphological identifications alone in archaeological remains. Finally, we present the first marine turtle molecular phylogeny using collagen (I) amino acid sequences and find our analyses match recent phylogenies based on nuclear and mitochondrial DNA. Our results highlight the advantage of using collagen fingerprinting to supplement morphological analyses of turtle bones and support the usefulness of this technique for assessing their past distributions across the Caribbean and Florida's Gulf Coast, especially in these tropical environments where DNA preservation may be poor.

Origin of the Aromatic Group of Cultivated Rice (Oryza sativa L.) Traced to the Indian Subcontinent.

The aromatic group of Asian cultivated rice is a distinct population with considerable genetic diversity on the Indian subcontinent and includes the popular Basmati types characterized by pleasant fragrance. Genetic and phenotypic associations with other cultivated groups are ambiguous, obscuring the origin of the aromatic population. From analysis of genome-wide diversity among over 1,000 wild and cultivated rice accessions, we show that aromatic rice originated in the Indian subcontinent from hybridization between a local wild population and examples of domesticated japonica that had spread to the region from their own center of origin in East Asia. Most present-day aromatic accessions have inherited their cytoplasm along with 29-47% of their nuclear genome from the local Indian rice. We infer that the admixture occurred 4,000-2,400 years ago, soon after japonica rice reached the region. We identify aus as the original crop of the Indian subcontinent, indica and japonica as later arrivals, and aromatic a specific product of local agriculture. These results prompt a reappraisal of our understanding of the emergence and development of rice agriculture in the Indian subcontinent.