You won’t find amphioxus listed as close relative on 23andMe, but this humble invertebrate chordate may have paved the way for the successful vertebrates we’ve become. Although amphioxus split from the vertebrates over 500 million years ago on the phylogenetic tree, it still can offer some clues as to how vertebrates acquired such unique and diverse gene regulation mechanisms such as pervasive CpG methylation and methylation-dependent regulatory elements.
In a massive team effort led by Manual Irimia, Jose Gómez-Skarmeta and Hector Escriva, 60+ researchers worked to compare genomic, transcriptomic, and epigenomic data between amphioxus and vertebrates to dissect the evolutionary timeline of vertebrate gene regulation. Why choose amphioxus? Senior investigator Héctor Escriva explains that “[the amphioxus] genome has evolved very slowly, without the [two] whole [genome] duplications present in the vertebrates. For this reason, the amphioxus can serve as a reference in evolutionary comparisons to understand our lineage.”
Thus, the amphioxus and vertebrate genomes share many orthologous genes and expression patterns. The team began by annotating the entire amphioxus genome. Next, putative regulatory elements in the amphioxus genome were identified using ATAC-seq, which were then compared with regulatory elements in various vertebrate genomes. You can check out the annotated amphioxus genome for yourself, and even compare it to other genomes through their dedicated server. But don’t miss out on the highlights below:
- Compared to vertebrates, the amphioxus genome has lower basal CpG methylation levels. However, the researchers discovered regulatory elements in the amphioxus genome that are activated in response to demethylation
- This epigenetic mechanism at these specific regulatory elements was previously thought to be unique to vertebrates
- Vertebrates have a significantly higher number of open chromatin regulatory sites per gene compared to amphioxus
- This difference is amplified for distal regulatory elements and in genes where multiple copies were retained after whole genome duplication (ohnologues)
- Genes that were retained in vertebrates after two whole genome duplication events were more likely to undergo specialization, with different ohnologues acquiring unique functions and regulatory elements
- Specialization resulted in an increase in both the number of regulatory elements and the rate of evolution of the protein coding sequences
- Strong specialization of ohnologues was most prevalent in vertebrate neural tissue
Co-senior author Manuel Irimia summed up their results: “First of all, we observed that generally speaking our gene regulation is much more complex than that of the invertebrates. The second difference is that we have copies of genes that originally performed only very general functions, but which in the vertebrates went on to specialise in much more specific functions, particularly in the brain”. Although the team gained valuable insights about the origins of epigenetic regulation, co-first author Ferdinand Marlétaz believes that “[w]e need more of these types of studies, to understand what the main differences are in terms of gene regulation in different animals”.
For a full family reunion with amphioxus, check out the published paper in Nature, November 2018.