Biology subjects

Fiddes, I.

Publications and source records attributed to Fiddes, I..

3 recordsLinked to original sources

bioRxiv2018

Pseudogenes in the mouse lineage: transcriptional activity and strain-specific history

Pseudogenes are ideal markers of genome remodeling. In turn, the mouse is an ideal platform for studying them, particularly with the availability of developmental transcriptional data and the sequencing of 18 strains. Here, we present a comprehensive genome-wide annotation of the pseudogenes in the mouse reference genome and associated strains. We compiled this by combining manual curation of over 10,000 pseudogenes with results from automatic annotation pipelines. Also, by comparing the human and mouse, we annotated 165 unitary pseudogenes in mouse, and 303 unitaries in human. We make all our annotation available through mouse.pseudogene.org. The overall mouse pseudogene repertoire (in the reference and strains) is similar to human in terms of overall size, biotype distribution (~80% processed/~20% duplicated) and top family composition (with many GAPDH and ribosomal pseudogenes). However, notable differences arise in the pseudogene age distribution, with multiple retro-transpositional bursts in mouse evolutionary history and only one in human. Furthermore, in each strain about a fifth of the pseudogenes are unique, reflecting strain-specific functions and evolution. Additionally, we find that ~15% of the pseudogenes are transcribed, a fraction similar to that for human, and that pseudogene transcription exhibits greater tissue and strain specificity compared to protein-coding genes. Finally, we show that highly transcribed parent genes tend to give rise to processed pseudogenes.

genomics↗

bioRxiv2018

Genome assembly and gene expression in the American black bear provides new insights into the renal response to hibernation.

The prevalence of chronic kidney disease (CKD) is rising worldwide and 10-15% of the global population currently suffers from CKD and its complications. Given the increasing prevalence of CKD there is an urgent need to find novel treatment options. The American black bear (Ursus americanus) copes with months of lowered kidney function and metabolism during hibernation without the devastating effects on metabolism and other consequences observed in humans. In a biomimetic approach to better understand kidney adaptations and physiology in hibernating black bears, we established a high-quality genome assembly. Subsequent RNA-Seq analysis of kidneys comparing gene expression profiles in black bears entering (late fall) and emerging (early spring) from hibernation identified 169 protein-coding genes that were differentially expressed. Of these, 101 genes were downregulated and 68 genes were upregulated after hibernation. Fold changes ranged from 1.8-fold downregulation (RTN4RL2) to 2.4-fold upregulation (CISH). Most notable was the upregulation of cytokine suppression genes (SOCS2, CISH, and SERPINC1) and the lack of increased expression of cytokines and genes involved in inflammation. The identification of these differences in gene expression in the black bear kidney may provide new insights in the prevention and treatment of CKD.

genomics↗

bioRxiv2017

Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes

Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 to 6 MYA, but that are absent in the Hominidae. In fact, Hominidae show between four-and seven-fold lower rates of nucleotide change and feature turnover in both neutral and functional sequences suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. For example, recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli. This process resulted in thousands of novel, species-specific CTCF binding sites. Our results demonstrate that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology.

genomics↗