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Following the draft sequence of the first human genome over 20 years ago, we have achieved unprecedented insights into the rules governing its evolution, often with direct translational relevance to specific diseases. However, staggering sequence complexity has also challenged the development of a more comprehensive understanding of human genome biology. In this context, interspecific genomic studies between humans and other animals have played a critical role in our efforts to decode human gene families. In this review, we focus on how the rapid surge of genome sequencing of both model and non-model organisms now provides a broader comparative framework poised to empower novel discoveries. We begin with a general overview of how comparative approaches are essential for understanding gene family evolution in the human genome, followed by a discussion of analyses of gene expression. We show how homology can provide insights into the genes and gene families associated with immune response, cancer biology, vision, chemosensation, and metabolism, by revealing similarity in processes among distant species. We then explain methodological tools that provide critical advances and show the limitations of common approaches. We conclude with a discussion of how these investigations position us to gain fundamental insights into the evolution of gene families among living organisms in general. We hope that our review catalyzes additional excitement and research on the emerging field of comparative genomics, while aiding the placement of the human genome into its existentially evolutionary context.

 

The bowfin (Amia calva) is a ray-finned fish that possesses a unique suite of ancestral and derived phenotypes, which are key to understanding vertebrate evolution. The phylogenetic position of bowfin as a representative of neopterygian fishes, its archetypical body plan and its unduplicated and slowly evolving genome make bowfin a central species for the genomic exploration of ray-finned fishes. Here we present a chromosome-level genome assembly for bowfin that enables gene-order analyses, settling long-debated neopterygian phylogenetic relationships. We examine chromatin accessibility and gene expression through bowfin development to investigate the evolution of immune, scale, respiratory and fin skeletal systems and identify hundreds of gene-regulatory loci conserved across vertebrates. These resources connect developmental evolution among bony fishes, further highlighting the bowfin’s importance for illuminating vertebrate biology and diversity in the genomic era.

 

Briefly considered extinct in the wild, the future of the Wyoming toad (Anaxyrus baxteri) continues to rely on captive breeding to supplement the wild population. Given its small natural geographic range and history of rapid population decline at least partly due to fungal disease, investigation of the diversity of key receptor families involved in the host immune response represents an important conservation need. Population decline may have reduced immunogenetic diversity sufficiently to increase the vulnerability of the species to infectious diseases. Here we use comparative transcriptomics to examine the diversity of toll-like receptors and major histocompatibility complex (MHC) sequences across three individual Wyoming toads. We find reduced diversity at MHC genes compared to bufonid species with a similar history of bottleneck events. Our data provide a foundation for future studies that seek to evaluate the genetic diversity of Wyoming toads, identify biomarkers for infectious disease outcomes, and guide breeding strategies to increase genomic variability and wild release successes. 

The emergence of a new phylogeny of ray-finned fishes at the turn of the twenty-first century marked a paradigm shift in understanding the evolutionary history of half of living vertebrates. We review how the new ray-finned fish phylogeny radically departs from classical expectations based on morphology. We focus on evolutionary relationships that span the backbone of ray-finned fish phylogeny, from the earliest divergences among teleosts and nonteleosts to the resolution of major lineages of Percomorpha. Throughout, we feature advances gained by the new phylogeny toward a broader understanding of ray-finned fish evolutionary history and the implications for topics that span from the genetics of human health to reconsidering the concept of living fossils. Additionally, we discuss conceptual challenges that involve reconciling taxonomic classification with phylogenetic relationships and propose an alternate higher-level classification for Percomorpha. Our review highlights remaining areas of phylogenetic uncertainty and opportunities for comparative investigations empowered by this new phylogenetic perspective on ray-finned fishes. 

Comparative genomic analyses have enormous potential for identifying key genes central to human health phenotypes, including those that promote cancers. In particular, the successful development of novel therapeutics using model species requires phylogenetic analyses to determine molecular homology. Accordingly, we investigate the evolutionary histories of anaplastic lymphoma kinase (ALK)—which can underlie tumorigenesis in neuroblastoma, non-small cell lung cancer, and anaplastic large-cell lymphoma—its close relative leukocyte tyrosine kinase (LTK) and their candidate ligands. Homology of ligands identified in model organisms to those functioning in humans remains unclear. Therefore, we searched for homologs of the human genes across metazoan genomes, finding that the candidate ligands Jeb and Hen-1 were restricted to non-vertebrate species. In contrast, the ligand AUG was only identified in vertebrates. We found two ALK-like and four AUG-like protein-coding genes in lamprey. Of these six genes, only one ALK-like and two AUG-like genes exhibited early embryonic expression that parallels model mammal systems. Two copies of AUG are present in nearly all jawed vertebrates. Our phylogenetic analysis strongly supports the presence of previously unrecognized functional convergences of ALK and LTK between actinopterygians and sarcopterygians—despite contemporaneous, highly conserved synteny of ALK and LTK. These findings provide critical guidance regarding the propriety of fish and mammal models with regard to model-organism-based investigation of these medically important genes. In sum, our results provide the phylogenetic context necessary for effective investigations of the functional roles and biology of these critically important receptors.