NEW YORK (GenomeWeb) – Two gene families have undergone extensive expansions in the genomes of parasitic nematodes, suggesting that they are involved in the evolution of parasitism, according to a new study.
Researchers led by the Wellcome Trust Sanger Institute's Matthew Berriman compared the genomes, transcriptomes, and proteomes of six nematodes from one clade, including a human pathogen, a facultatively parasitic worm, and a free-living worm. As they reported today in Nature Genetics, expansions of the astacin-like and SCP/TAPS protein gene families were associated with the evolution of parasitism. Further, by examining the parasitic and free-living stages of the worms' lifecycle, the researchers found that these gene families are also upregulated during the parasitic stages.
"Understanding the molecular and genetic differences between parasitic and free-living organisms is of fundamental biological interest and is essential to identifying novel drug targets and other methods to control parasitic nematodes and the diseases that they cause," Berriman and his colleagues wrote in their paper
Strongyloides species are part of a clade of nematodes that includes free-living worms as well as ones that are parasites of invertebrates, facultative parasites of vertebrates, and obligate parasites of vertebrates. Two Strongyloides species — S. stercoralis and S. fuelleborn — infect between 100 million and 200 million people worldwide, the researchers noted.
Typically, they added, the Strongyloides lifecycle alternates between free-living and parasitic generations. The parasitic generation lives in the small intestine of its host, and its offspring develop outside of the host into either infective third-stage larvae (iL3s) or into a sexually reproducing adult generation that can also produce iL3s. These iL3s can move through the skin of the host to its gut and develop into parasitic adults to begin the cycle anew.
Berriman and his colleagues sequenced the genomes of six nematodes, including four Strongyloides — S. stercoralis, S. ratti, S. venezuelensis, and S. papillosus — as well as Parastrongyloides trichosuri and the free-living Rhabditophanes. The S. ratti genome, they noted, is a high-quality 43-megabase reference genome, while the other are high-quality draft genomes.
These nematode genomes contain 12,500 genes to 18,500 genes, the researchers estimated.
Some gene families, they reported, underwent expansions in parasitic worms. Using Ensemble Compara, the researchers identified orthologs and gene families in these nematodes and an additional eight outgroup species that cover an additional four nematode clades. Based on this, they found that the branch leading to the parasitic nematodes — the branch that includes the Strongyloides and Parastrongyloides — acquired 1,075 gene families.
The two most expanded Strongyloides gene families encoded astacin-like and SCP/TAPS proteins, the researchers reported.
In particular, they found that the astacin family of metalloproteases was the most expanded: the Strongyloides-Parastrongyloides species had between 184 and 387 copies of that family, as compared to Rhabditophanes and the eight outgroup species. This expansion tracks with the evolution of parasitism, the researchers said.
Astacins are metallopeptidases and are suspected to have a role in tissue migration by infective nematode larvae, while SCP/TAPS proteins are immunomodulatory proteins, the researchers noted.
Other gene families such as acetylcholinesterase-encoding genes and receptor-type tyrosine phosphatases were also expanded in Strongyloides-Parastrongyloides as compared to Rhabditophanes.
To identify genes and gene families important for a parasitic lifestyle, Berriman and his colleagues compared the transcriptomes and proteomes of S. ratti and S. stercoralis from their parasitic and free-living female stages.
While some 900 S. ratti and nearly 1,200 S. stercoralis genes were upregulated in the parasitic females as compared to the free-living ones, this list of differentially expressed genes was dominated members of the astacin-like and SCP/TAPS protein gene families, the researchers reported.
At the protein level, some 570 proteins were upregulated in parasitic females. However, the researchers only noted a modest overlap between the transcriptome and somatic proteome. They attributed this low matchup to post-translational processes like the secretion of gene products.
When they examined the excretory/secretory proteome, they found a further 882 proteins and a better match with the transcriptome — the ES proteome, they added, contained 25 astacin and 14 SCP/TAPS gene products.
This, researchers said, indicates that the expansion of protease-encoding genes and the secretion of proteases might be a key part of nematode parasitism. They further suggested that proteinases could help the worm penetrate host tissues, acquire resources from the host, and protect it from the host.
The upregulated genes were often physically clustered near one another in the genome, the researchers noted. This likely stems from tandem gene duplications and could suggest a regulatory mechanisms for parasite development, they added.
"We find that a preponderance of the genes that are expanded in parasitic species are specifically used in the parasitic stages and are within genomic clusters, concentrated in regions of chromosome II," Berriman and his colleagues wrote. "This is consistent with the idea that the within-host stages of parasitic nematodes deploy a specific biology that enables them to be successful parasite."