NEW YORK (GenomeWeb News) – A study published online today in Nature suggests that the genome of the elephant shark, Callorhinchus milii, is evolving more slowly than that of any other vertebrate sequenced so far and may provide clues to the advent of some adaptive immune features.
"The slow-evolving genome of the elephant shark is probably the best proxy for the ancestor of all jawed vertebrates that became extinct a long time ago," Byrappa Venkatesh, research director of the Agency for Science, Technology and Research (A*STAR )'s Institute of Molecular and Cell Biology, said in a statement.
Venkatesh was part of an international team led by investigators at Washington University, A*STAR, and the National University of Singapore that sequenced and assembled the nearly one billion base elephant shark genome using a combination of Roche 454 and Sanger sequencing.
Together with transcriptome sequences generated on a third platform, the genome provided the researchers with a look at the protein-coding genes, regulatory sequences, and genome structure present in the cartilaginous fish. Meanwhile, comparisons with sequences from other vertebrates made it possible to find new clues about the advent of bone formation and immune function — particularly by the adaptive immune system used to combat bacterial pathogens and other infectious agents.
Given such findings — as well as the cartilaginous fish's place in the animal tree — Venkatesh said the new genome "is a cornerstone for improving our understanding of the development and physiology of human and other vertebrates as illustrated by our analysis of the skeletal system and immune system genes."
Found primarily in deep ocean waters near Australia and New Zealand, the elephant shark uses the trunk-like snout that earned the fish its name to root up bottom-dwelling crustaceans. Beyond interest in understanding the biology of the elephant shark itself, study authors noted, its genome is expected to help in interpreting information about other jawed, cartilaginous fish as well as jawed creatures from the sister lineage of bony fish.
As such, the animal is a "critical outlier for understanding the evolution and diversity of bony vertebrates, including humans," senior author Wesley Warren, a genetics researcher with Washington University's Genome Institute, explained in a statement.
"Although cartilaginous vertebrates and bony vertebrates diverged about 450 million years ago, with the elephant shark genome in hand, we can begin to identify key genetic adaptations in the evolutionary tree," Warren said.
Venkatesh, Warren, and colleagues turned to Roche 454 GS FLX Titanium sequencing and traditional Sanger sequencing to decipher the sequence of elephant shark genomic DNA isolated from testes tissue of a male fish from Tasmania. To that they added transcriptome sequences generated for 10 elephant shark tissues using Illumina's GAIIx instrument.
Using that data, the team put together a 937 million base genome assembly containing 18,872 predicted protein-coding genes and almost 700 microRNA genes. The latter included representatives from nearly two-dozen miRNA families that are found in mammals but lost in the bony fish group.
The researchers also detected 63,877 non-coding sequences that have been conserved between the elephant shark and animals in the sister lineage of bony vertebrates.
Almost all of those potential regulatory elements are absent in the genomes of the sea lamprey and other animals that diverged prior to the advent of jawed animals, they noted, suggesting that a suite of regulatory changes may have accompanied so-called gnathostome (jawed vertebrate) evolution.
Along with their phylogenetic analysis supporting the notion that the elephant shark belongs to a sister lineage to bony vertebrates with jaws, the researchers also went on to compare substitution rates and gene family content in the elephant shark genome with those of other animals.
For instance, they found evidence that the elephant shark genome has undergone fairly modest changes over evolutionary time — meaning it may share many features with the genome found in the common ancestor of both the jawed, cartilaginous fish and the bony vertebrates.
The team focused in on the genetic basis of some of the elephant shark's specific biological features, too.
Consistent with the fish's non-bony skeleton, the investigators failed to find genes coding for a family of secreted calcium-binding phosphoproteins that are believed to contribute to bone formation in bony fish and other vertebrates.
The elephant shark genome was also missing certain components of the adaptive immune system, researchers reported, including most T helper cells, the CD4 co-receptor gene, and genes coding for related transcription factors, cytokines, and cytokine receptors.
"[T]he adaptive immune system of cartilaginous fishes possesses a highly restricted subsets of T helper cells (perhaps only one) with unconventional antigen-binding properties," they wrote, noting that the elephant shark genome "presents a new model for understanding the origin of adaptive immunity."