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Genome Analysis Reveals Horizontal Gene Transfer Events in Vertebrates

NEW YORK (GenomeWeb) – Through genome-scale comparisons and phylogenetic analysis, researchers from the University of Cambridge report that they've uncovered numerous instances of horizontal gene transfer in invertebrates as well as in vertebrates.

As the researchers reported in Genome Biology today, they compared the genomes and transcriptomes of more than two dozen animal species encompassing flies, nematodes, and primates and found that the expression of horizontally acquired genes is common. Many of these genes, they added, have roles in metabolism, immune response, protein modification, and more. Further, they noted that such acquisition seems to be ongoing in flies and worms.

"This is the first study to show how widely horizontal gene transfer occurs in animals, including humans, giving rise to tens or hundreds of active 'foreign' genes," Cambridge's Alastair Crisp said in a statement. "Surprisingly, far from being a rare occurrence, it appears that HGT has contributed to the evolution of many, perhaps all, animals and that the process is ongoing, meaning that we may need to re-evaluate how we think about evolution."

HGT has been shown to occur widely in bacteria and unicellular prokaryotes, but has been more rarely and more controversially found in multicellular organisms, particularly when it comes to vertebrates and humans.

To search for evidence of HGT, Crisp and his colleagues studied the genomes of 12 Drosophila, four Caenorhabditis, and 10 primate species. For each transcribed gene, they generated an HGT index score that reflected how well that gene aligned to metazoan versus non-metazoan sequences — the higher the score, the better the alignment to non-metazoan sources.

They then divvied these putatively horizontally acquired genes into three classes, A, B, and C, based on their scores and the presence or absence of homologs in related species. They then validated those findings though phylogenetic analysis.

From this, they reported that Caenorhabditis has 173 class C, 127 class B, and 68 class A foreign genes, and Drosophila has 40 class C, 25 class B, and four class A foreign genes. Meanwhile, primates have 109 class C, 79 class B, and 32 class A foreign genes.

Bacteria and protists were the most common gene donors, though some genes came from fungi and viruses.

As a check against contamination, the researchers tested whether these putative HGT-acquired genes were present on the same genomic scaffolds as metazoan-origin genes, and found that most were present alongside native genes.

The first human genome report, the researchers said, highlighted 223 protein sequences encoded in the human genome that appeared to be from bacteria, though these were largely dismissed.

Here, Crisp and his colleagues confirmed 17 of those previously reported foreign genes.

One of those genes, they noted, encodes the hyaluronan synthases, which are of fungal origin. HAS genes, the researchers added, are found in numerous chordates, though not in non-chordate metazoans, suggesting that the transfer event occurred in a common ancestor of Chordata before undergoing duplication events.

They also identified the fat mass and obesity-related FTO gene, the ABO blood group gene, and others as horizontally transferred genes in humans.

Overall, horizontally transferred genes tend to encode enzymes, the researchers found. A Gene Ontology analysis revealed that foreign genes appear to have roles in metabolism, immune response, macromolecular modification, and more.

To place the timing of these HGT events, Crisp and his colleagues mapped the foreign ortholog groups for each taxon to their phylogenetic trees. For Drosophila and Caenorhabditis, the branch length corresponded with the number of HGT events along those branches, suggesting that HGT is both old and ongoing in these species.

However, the pattern was different for primates, as most of the foreign groups mapped to the base of the phylogenetic tree, indicating that the HGT events occurred in the span of time between the common ancestor of Chordata and the common ancestors of primates.

 "Interestingly, overall levels of HGT do not appear to be conspicuously different in vertebrates and invertebrates," Crisp and his colleagues added. "This is surprising given the difference in complexity between the groups, but may be explained by the observed older HGT in primates, suggesting that the vertebrate HGT may have occurred at an earlier stage of vertebrate evolution."

 The researchers also noted that they couldn't fully rule out the possibility that these foreign genes were inherited by vertical descent and then lost from other metazoan species.

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