Darwinian genomics and diversity in the tree of life

Abstract

Genomics encompasses the entire tree of life, both extinct and extant, and the evolutionary processes that shape this diversity. To date, genomic research has focused on humans, a small number of agricultural species, and established laboratory models. Fewer than 18,000 of ∼2,000,000 eukaryotic species (<1%) have a representative genome sequence in GenBank, and only a fraction of these have ancillary information on genome structure, genetic variation, gene expression, epigenetic modifications, and population diversity. This imbalance reflects a perception that human studies are paramount in disease research. Yet understanding how genomes work, and how genetic variation shapes phenotypes, requires a broad view that embraces the vast diversity of life. We have the technology to collect massive and exquisitely detailed datasets about the world, but expertise is siloed into distinct fields. A new approach, integrating comparative genomics with cell and evolutionary biology, ecology, archaeology, anthropology, and conservation biology, is essential for understanding and protecting ourselves and our world. Here, we describe potential for scientific discovery when comparative genomics works in close collaboration with a broad range of fields as well as the technical, scientific, and social constraints that must be addressed.

Keywords: biodiversity; comparative genomics; evolution; genomics; natural models.

Fig. 1.

Species diversity in the Sequence Read Archive (SRA). The amount of human data exceeds that of the next top 10 species, measured as (A) terabases and (B) individuals sequenced. (C) The human proportion increased between 2010 and 2020, and (D) the proportion from species without known commercial/medical relevance (“other”) dropped. (E) A tiny proportion of IUCN-recognized (80) species have a reference genome (red) or are otherwise represented in the SRA (dark gray). Retrieved November 14, 2020.

Fig. 2.

Different types of study populations have different strengths. “Diversity”: genetic diversity in populations, ranging from inbred (e.g., laboratory mice) to outbred/highly diverse. Humans (midpoint) are outbred but less diverse than many species. “Complexity”: genetic complexity of traits; low in the laboratory mouse, with controlled genetic background and environment, and high in humans, where most traits are complex. “Phenotyping”: ease of collecting phenotype data, ranging from only noninvasive phenotyping in natural environments, to invasive laboratory phenotyping. In humans (midpoint), resources like electronic medical records make it possible, but not easy, to collect detailed phenotypes at scale. “Sampling”: ease of collecting samples, ranging from only minimally invasive sampling in wild-caught individuals, to populations where euthanasia and tissue collection are feasible. “Sample size”: number of individuals that can be sampled, ranging from <100 (endangered species or laboratory animals requiring costly care) to millions (humans). “Function”: potential for functional genomics (epigenomics, cellular and organoid models, genetic engineering, and so forth). In humans, cellular models are well developed, but organism-level experimentation is not possible.