1. Evolutionary Biology
  2. Genetics and Genomics
Download icon

Immune genes are hotspots of shared positive selection across birds and mammals

  1. Allison J Shultz  Is a corresponding author
  2. Timothy Sackton  Is a corresponding author
  1. Harvard University, United States
Research Article
  • Cited 40
  • Views 5,301
  • Annotations
Cite this article as: eLife 2019;8:e41815 doi: 10.7554/eLife.41815

Abstract

Consistent patterns of positive selection in functionally similar genes can suggest a common selective pressure across a group of species. We use alignments of orthologous protein-coding genes from 39 species of birds to estimate parameters related to positive selection for 11,000 genes conserved across birds. We show that functional pathways related to the immune system, recombination, lipid metabolism, and phototransduction are enriched for positively selected genes. By comparing our results with mammalian data, we find a significant enrichment for positively selected genes shared between taxa, and that these shared selected genes are enriched for viral immune pathways. Using pathogen-challenge transcriptome data, we show that genes up-regulated in response to pathogens are also enriched for positively selected genes. Together, our results suggest that pathogens, particularly viruses, consistently target the same genes across divergent clades, and that these genes are hotspots of host-pathogen conflict over deep evolutionary time.

Data availability

All data generated and analyzed during this study, including all source data for all figures are included in the manuscript, supporting files, Dryad repository (doi:10.5061/dryad.kt24554). All alignments used to perform analyses of PAML and HyPhy results are also available in the Dryad repository. Computing scripts for all analyses are available here: https://github.com/ajshultz/avian-immunity.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Allison J Shultz

    FAS Informatics, Harvard University, Cambridge, United States
    For correspondence
    allisonjshultz@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2089-4086
  2. Timothy Sackton

    FAS Informatics, Harvard University, Cambridge, United States
    For correspondence
    tsackton@g.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1673-9216

Funding

The authors declare that there was no external funding received for this work.

Reviewing Editor

  1. Christian R Landry, Université Laval, Canada

Publication history

  1. Received: September 6, 2018
  2. Accepted: January 8, 2019
  3. Accepted Manuscript published: January 8, 2019 (version 1)
  4. Version of Record published: January 18, 2019 (version 2)

Copyright

© 2019, Shultz & Sackton

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 5,301
    Page views
  • 711
    Downloads
  • 40
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Evolutionary Biology
    2. Genetics and Genomics
    Milton Tan et al.
    Research Article Updated

    Chondrichthyes (cartilaginous fishes) are fundamental for understanding vertebrate evolution, yet their genomes are understudied. We report long-read sequencing of the whale shark genome to generate the best gapless chondrichthyan genome assembly yet with higher contig contiguity than all other cartilaginous fish genomes, and studied vertebrate genomic evolution of ancestral gene families, immunity, and gigantism. We found a major increase in gene families at the origin of gnathostomes (jawed vertebrates) independent of their genome duplication. We studied vertebrate pathogen recognition receptors (PRRs), which are key in initiating innate immune defense, and found diverse patterns of gene family evolution, demonstrating that adaptive immunity in gnathostomes did not fully displace germline-encoded PRR innovation. We also discovered a new toll-like receptor (TLR29) and three NOD1 copies in the whale shark. We found chondrichthyan and giant vertebrate genomes had decreased substitution rates compared to other vertebrates, but gene family expansion rates varied among vertebrate giants, suggesting substitution and expansion rates of gene families are decoupled in vertebrate genomes. Finally, we found gene families that shifted in expansion rate in vertebrate giants were enriched for human cancer-related genes, consistent with gigantism requiring adaptations to suppress cancer.

    1. Evolutionary Biology
    2. Immunology and Inflammation
    Srijan Seal et al.
    Review Article

    Researchers worldwide are repeatedly warning us against future zoonotic diseases resulting from humankind’s insurgence into natural ecosystems. The same zoonotic pathogens that cause severe infections in a human host frequently fail to produce any disease outcome in their natural hosts. What precise features of the immune system enable natural reservoirs to carry these pathogens so efficiently? To understand these effects, we highlight the importance of tracing the evolutionary basis of pathogen tolerance in reservoir hosts, while drawing implications from their diverse physiological and life-history traits, and ecological contexts of host-pathogen interactions. Long-term co-evolution might allow reservoir hosts to modulate immunity and evolve tolerance to zoonotic pathogens, increasing their circulation and infectious period. Such processes can also create a genetically diverse pathogen pool by allowing more mutations and genetic exchanges between circulating strains, thereby harboring rare alive-on-arrival variants with extended infectivity to new hosts (i.e., spillover). Finally, we end by underscoring the indispensability of a large multidisciplinary empirical framework to explore the proposed link between evolved tolerance, pathogen prevalence, and spillover in the wild.