Systematic analysis of insertions and deletions specific to nematode proteins and their proposed functional and evolutionary relevance

Abstract

Background: Amino acid insertions and deletions in proteins are considered relatively rare events, and their associations with the evolution and adaptation of organisms are not yet understood. In this study, we undertook a systematic analysis of over 214,000 polypeptides from 32 nematode species and identified insertions and deletions unique to nematode proteins in more than 1000 families and provided indirect evidence that these alterations are linked to the evolution and adaptation of nematodes.

Results: Amino acid alterations in sequences of nematodes were identified by comparison with homologous sequences from a wide range of eukaryotic (metzoan) organisms. This comparison revealed that the proteins inferred from transcriptomic datasets for nematodes contained more deletions than insertions, and that the deletions tended to be larger in length than insertions, indicating a decreased size of the transcriptome of nematodes compared with other organisms. The present findings showed that this reduction is more pronounced in parasitic nematodes compared with the free-living nematodes of the genus Caenorhabditis. Consistent with a requirement for conservation in proteins involved in the processing of genetic information, fewer insertions and deletions were detected in such proteins. On the other hand, more insertions and deletions were recorded for proteins inferred to be involved in the endocrine and immune systems, suggesting a link with adaptation. Similarly, proteins involved in multiple cellular pathways tended to display more deletions and insertions than those involved in a single pathway. The number of insertions and deletions shared by a range of plant parasitic nematodes were higher for proteins involved in lipid metabolism and electron transport compared with other nematodes, suggesting an association between metabolic adaptation and parasitism in plant hosts. We also identified three sizable deletions from proteins found to be specific to and shared by parasitic nematodes, which, given their uniqueness, might serve as target candidates for drug design.

Conclusion: This study illustrates the significance of using comparative genomics approaches to identify molecular elements unique to parasitic nematodes, which have adapted to a particular host organism and mode of existence during evolution. While the focus of this study was on nematodes, the approach has applicability to a wide range of other groups of organisms.

Figure 1

Nematode species and number of polypeptides per species used in the analysis. The species are organized based on their SSU rRNA phylogeny [29]. Numbers following the species names are number of EST-derived contigs or full-length proteins (asterix). The color background is based on the trophic ecology: Green, plant parasitic nematodes; Blue, free-living nematodes, Red, animal and/or human parasites.

Figure 2

Identification and analysis of insertions and deletions specific to nematode proteins. The results obtained from each step of the workflow are shown.

Figure 3

Frequency distribution of sizes of insertions and deletions. Fifty percent of deletions are longer than 10 residues, whereas only 17% of insertions are of a comparable length.

Figure 4

Distribution of insertions/deletions of 173 protein families that have at least two members per clade. A total of 2,236 deletions and 636 insertions were identified. ^a, insertions restricted to this clade; ^b, deletions restricted to this clade. The species are organized based on their SSU rRNA phylogeny [29].

Figure 5

Characteristics of protein family NF_0309_0623. A. Multiple alignment of the members of this protein family (the alignment has been trimmed for a better view). This family has proteins that originate from species spanning 3 clades. It encodes mitochondrial carrier protein that belongs to MC family, involved in Environmental Information Processing (based on Panther; [92]). Accession numbers of sequences used are: XP_746931.1, CAD60708.1, XP_427233.2, NP_729803.1, XP_394090.1, CAG07711.1, XP_715902.1, XP_217310.3, XP_001387442, XP_001492793, XP_001649449, NP_001039791, XP_001247964, NP_001008081.1, XP_001163052, NP_998284.1, EDL38228.1, XP001376701, BAE61781.1, XP_001084129, XP_001604399, XP_001374602, NP_984088.1, AAB17185.1, XP_308217.3, EAW69088.1, XP_854738.1, NP_001085887, XP_001361631, XP_971944.1, XP_001273074. B. Structure model 2C3E from Bos taurus mitochondrial ADP/ATP carrier was used to show the nematode-specific deletion (marked in red).