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Abstract Evolutionary perspectives on the deployment of immune factors following infection have been shaped by studies on a limited number of biomedical model systems with a heavy emphasis on vertebrate species. Although their contributions to contemporary immunology cannot be understated, a broader phylogenetic perspective is needed to understand the evolution of immune systems across Metazoa. In our study, we leverage differential gene expression analyses to identify genes implicated in the antiviral immune response of the acorn worm hemichordate, Saccoglossus kowalevskii, and place them in the context of immunity evolution within deuterostomes—the animal clade composed of chordates, hemichordates, and echinoderms. Following acute exposure to the synthetic viral double-stranded RNA analog, poly(I:C), we show that S. kowalevskii responds by regulating the transcription of genes associated with canonical innate immunity signaling pathways (e.g., nuclear factor κB and interferon regulatory factor signaling) and metabolic processes (e.g., lipid metabolism), as well as many genes without clear evidence of orthology with those of model species. Aggregated across all experimental time point contrasts, we identify 423 genes that are differentially expressed in response to poly(I:C). We also identify 147 genes with altered temporal patterns of expression in response to immune challenge. By characterizing the molecular toolkit involved in hemichordate antiviral immunity, our findings provide vital evolutionary context for understanding the origins of immune systems within Deuterostomia. 

Abstract Sequence annotation is fundamental for studying the evolution of protein families, particularly when working with nonmodel species. Given the rapid, ever-increasing number of species receiving high-quality genome sequencing, accurate domain modeling that is representative of species diversity is crucial for understanding protein family sequence evolution and their inferred function(s). Here, we describe a bioinformatic tool called Taxon-Informed Adjustment of Markov Model Attributes (TIAMMAt) which revises domain profile hidden Markov models (HMMs) by incorporating homologous domain sequences from underrepresented and nonmodel species. Using innate immunity pathways as a case study, we show that revising profile HMM parameters to directly account for variation in homologs among underrepresented species provides valuable insight into the evolution of protein families. Following adjustment by TIAMMAt, domain profile HMMs exhibit changes in their per-site amino acid state emission probabilities and insertion/deletion probabilities while maintaining the overall structure of the consensus sequence. Our results show that domain revision can heavily impact evolutionary interpretations for some families (i.e., NLR’s NACHT domain), whereas impact on other domains (e.g., rel homology domain and interferon regulatory factor domains) is minimal due to high levels of sequence conservation across the sampled phylogenetic depth (i.e., Metazoa). Importantly, TIAMMAt revises target domain models to reflect homologous sequence variation using the taxonomic distribution under consideration by the user. TIAMMAt’s flexibility to revise any subset of the Pfam database using a user-defined taxonomic pool will make it a valuable tool for future protein evolution studies, particularly when incorporating (or focusing) on nonmodel species. 

Apes possess two sex chromosomes—the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility¹. The X chromosome is vital for reproduction and cognition². Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements—owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species. 

ABSTRACT We present haplotype-resolved reference genomes and comparative analyses of six ape species, namely: chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. We achieve chromosome-level contiguity with unparalleled sequence accuracy (<1 error in 500,000 base pairs), completely sequencing 215 gapless chromosomes telomere-to-telomere. We resolve challenging regions, such as the major histocompatibility complex and immunoglobulin loci, providing more in-depth evolutionary insights. Comparative analyses, including human, allow us to investigate the evolution and diversity of regions previously uncharacterized or incompletely studied without bias from mapping to the human reference. This includes newly minted gene families within lineage-specific segmental duplications, centromeric DNA, acrocentric chromosomes, and subterminal heterochromatin. This resource should serve as a definitive baseline for all future evolutionary studies of humans and our closest living ape relatives.