Evolutionary Characterization of the Short Protein SPAAR

Microproteins (<100 amino acids) are receiving increasing recognition as important participants in numerous biological processes, but their evolutionary dynamics are poorly understood. SPAAR is a recently discovered microprotein that regulates muscle regeneration and angiogenesis through interactions with conserved signaling pathways. Interestingly, SPAAR does not belong to any known protein family and has known homologs exclusively among placental mammals. This lack of distant homology could be caused by challenges in homology detection of short sequences, or it could indicate a recent de novo emergence from a noncoding sequence. By integrating syntenic alignments and homology searches, we identify SPAAR orthologs in marsupials and monotremes, establishing that SPAAR has existed at least since the emergence of mammals. SPAAR shows substantial primary sequence divergence but retains a conserved protein structure. In primates, we infer two independent evolutionary events leading to the de novo origination of 5′ elongated isoforms of SPAAR from a noncoding sequence and find evidence of adaptive evolution in this extended region. Thus, SPAAR may be of ancient origin, but it appears to be experiencing continual evolutionary innovation in mammals.

A New Intronic Variant in ECEL1 in Two Patients with Distal Arthrogryposis Type 5D

Distal Arthrogryposis type 5D (DA5D) is characterized by congenital contractures involving the distal joints, short stature, scoliosis, ptosis, astigmatism, and dysmorphic features. It is inherited in an autosomal recessive manner, and it is a result of homozygous or compound heterozygous variants in the ECEL1 gene. Here, we report two patients of Sardinian origin harboring a new intronic homozygous variant in ECEL1 (c.1507-9G>A), which was predicted to affect mRNA splicing by activating a cryptic acceptor site. The frequency of the variant is very low in the general human population, and its presence in our families can be attributed to a founder effect. This study provides an updated review of the known causative mutations of the ECEL1 gene, enriching the allelic spectrum to include the noncoding sequence.

The mole genome reveals regulatory rearrangements associated with adaptive intersexuality

Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.

Complete Coding Sequence of Usutu Virus Strain Gracula religiosa/U1609393/Belgium/2016 Obtained from the Brain Tissue of an Infected Captive Common Hill Myna (Gracula religiosa)

ABSTRACT The complete and annotated coding sequence and partial noncoding sequence of an Usutu virus genome were sequenced from RNA extracted from a clinical brain tissue sample obtained from a common hill myna (Gracula religiosa), demonstrating close homology with Usutu viruses circulating in Europe.