Biology subjects

Damas, J.

Publications and source records attributed to Damas, J..

7 recordsLinked to original sources

bioRxiv2026

Side-necked turtle genomes reveal chromosomal dynamics, skeletal innovation and cancer resistance

Turtles exhibit a highly derived body plan, exceptional longevity, cancer resistance, and striking diversity in karyotypes and sex determination systems. However, the genomic basis of these innovations remains unresolved, largely because reference genomes were lacking for one of two extant turtle clades, the side-necked turtles (Pleurodira). As part of the Vertebrate Genomes Project, we generated seven reference-quality Pleurodira genomes and reconstructed the most comprehensive genome-wide turtle phylogeny. Combining demographic inference with historical climate and biome reconstructions indicates that ancient climate fluctuations shaped long-term population dynamics, while recent declines mainly reflect population structure. Ancestral genome reconstructions reveal that rare bursts of chromosome fusions and fissions, likely facilitated by repetitive elements, drove turtle karyotype diversity. By identifying sex chromosomes and tracing their evolutionary history, we resolve a long-standing debate and demonstrate a single origin of genetic sex determination in Chelidae on a microchromosome over 80 million years ago. Contrary to previous hypotheses, we find no evidence of coevolution between genetic sex determination and chromosome number in turtles. Comparative genomic analyses further identify gene losses and signatures of adaptive evolution associated with key turtle traits. Gene losses causing disproportionate dwarfism phenotypes may have contributed to skeletal adaptations underlying the compact turtle body plan. In addition, gene losses and adaptive changes in stress response and tumor suppressor pathways likely enhance oxidative stress tolerance and cancer resistance. Together, these findings illuminate turtle genome evolution, revealing chromosomal dynamics, sex chromosome evolution, molecular insights into skeletal innovation and cancer resistance, and implicate gene losses as a recurrent contributor to evolutionary novelty.

genomics↗

bioRxiv2023

FLAG: Find, Label Annotate Genomes, a fully automated tool for genome gene structural and functional annotation of highly fragmented non-model species

Recent advances in long-read sequencing technologies and the efforts of projects aimed at increasing the universe of sequenced reference genomes have led to a growth in the number of whole genomes sequenced for non-model organisms. Still, 81% of the over 36,000 unique publicly available eukaryotic genomes in the NCBI database lack gene structure annotations (1). While there are many open-source tools available for each step in the annotation process, many of these tools are designed for chromosomal assemblies with available transcript data from the same or very closely related organisms. Here we present "Find, Label, Annotate Genomes" (FLAG), a fully automated genome annotation workflow. FLAG (i) works on any computing environment, (ii) runs automatically without initial training data, (iii) generates structural and functional annotations, (iv) performs accurately with fragmented genomes, (v) does not require species-specific extrinsic evidence (transcript sequences) and (vi) includes quality control steps to evaluate annotation completeness. We compared the gene annotations generated by FLAG and publicly available annotations from 12 eukaryotic organisms, including 1 plant, 8 living animals, and 1 extinct animal. In fragmented genomes, FLAG annotations provided an average of 18% increase in complete BUSCO scores and 15x lower error rate for the predicted number of protein-coding genes when compared to published BRAKER2 annotations. With FLAG-Refiner further improved results by decreasing the error rate to 17x lower when compared to published BRAKER2 annotations. In high-quality model organisms, FLAG demonstrates comparable results to those of the NCBI EGAP pipeline, underscoring its robustness and accuracy in gene prediction across diverse taxa and assembly qualities.

bioinformatics↗

bioRxiv2023

Evolutionary constraint and innovation across hundreds of placental mammals

Evolutionary constraint and acceleration are powerful, cell-type agnostic measures of functional importance. Previous studies in mammals were limited by species number and reliance on human-referenced alignments. We explore the evolution of placental mammals, including humans, through reference-free whole-genome alignment of 240 species and protein-coding alignments for 428 species. We estimate 10.7% of the human genome is evolutionarily constrained. We resolve constraint to single nucleotides, pinpointing functional positions, and refine and expand by over seven-fold the catalog of ultraconserved elements. Overall, 48.5% of constrained bases are as yet unannotated, suggesting yet-to-be-discovered functional importance. Using species-level phenotypes and an updated phylogeny, we associate coding and regulatory variation with olfaction and hibernation. Focusing on biodiversity conservation, we identify genomic metrics that predict species at risk of extinction.

genomics↗

bioRxiv2022

A genomic timescale for placental mammal evolution

The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis of genetic variation across an alignment of 241 placental mammal genome assemblies, addressing prior concerns regarding limited genomic sampling across species. We compared neutral genome-wide phylogenomic signal using concatenation and coalescent-based approaches, interrogated phylogenetic variation across chromosomes and analyzed extensive catalogs of structural variants. Interordinal relationships exhibit relatively low rates of phylogenomic conflict across diverse datasets and analytical methods. Conversely, X-chromosome versus autosome conflicts characterize multiple independent clades that radiated during the Cenozoic. Genomic timetrees reveal an accumulation of cladogenic events before and immediately following the KPg boundary implying important roles for Cretaceous continental vicariance and the KPg extinction in the placental radiation. One-Sentence SummaryA comprehensive whole genome phylogeny of extant placental mammals reveals timing and patterns of ordinal diversification.

evolutionary biology↗

bioRxiv2021

A mitotic screen in Indian muntjac cells unveils how Augmin drives kinetochore fiber maturation

Chromosome segregation in mammals relies on the maturation of a thick bundle of kinetochore-attached microtubules known as k-fibers. How k-fibers mature from initial kinetochore-microtubule attachments remains a fundamental question. By combining functional perturbations in Indian muntjac, a placental mammal with the lowest known chromosome number (n=3) and distinctively large kinetochores, with fixed- and subsecond live-cell super-resolution CH-STED nanoscopy, we uncovered the mechanism by which Augmin mediates k-fiber maturation. Augmin promoted kinetochore microtubule turnover by sustaining microtubule formation from kinetochores and poleward flux, regardless of pioneer centrosomal microtubules. Tracking of microtubule growth events within individual k-fibers revealed a wide angular dispersion, consistent with Augmin-mediated branched microtubule nucleation. Augmin depletion reduced the frequency of microtubule growth events within k-fibers and hampered normal repair after acute k-fiber injury by laser microsurgery. Our work underscores the contribution of microtubule formation from kinetochores and Augmin-mediated microtubule amplification for k-fiber maturation and spindle assembly in mammals.

cell biology↗

bioRxiv2020

Towards complete and error-free genome assemblies of all vertebrate species

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are only available for a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling the most accurate and complete reference genomes to date. Here we summarize these developments, introduce a set of quality standards, and present lessons learned from sequencing and assembling 16 species representing major vertebrate lineages (mammals, birds, reptiles, amphibians, teleost fishes and cartilaginous fishes). We confirm that long-read sequencing technologies are essential for maximizing genome quality and that unresolved complex repeats and haplotype heterozygosity are major sources of error in assemblies. Our new assemblies identify and correct substantial errors in some of the best historical reference genomes. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an effort to generate high-quality, complete reference genomes for all ~70,000 extant vertebrate species and help enable a new era of discovery across the life sciences.

genomics↗

bioRxiv2020

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low. Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evidence of positive selection in ACE2 in multiple species, including bats. Utilized appropriately, our results may lead to the identification of intermediate host species for SARS-CoV-2, justify the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.

genomics↗