Friday, April 13, 2012

New genes, old function

Ken mused a while back here on MT about the improbability of finding a DNA sequence that had no similarity to sequence from any known organism.  And this is as we'd expect, if all life on Earth shares a common ancestor, and nothing that has been discovered since Darwin first proposed this in 1859 suggests otherwise.

So, why are researchers reporting DNA enzyme sequences that don't appear to be homologous to any known sequences for similar enzymes?  Fran├žois Delavat et al. have sequenced genes from organisms found in an acid mine drainage, organisms that are resistant to being cultured (i.e., that can't be readily grown up in the lab), looking for novel genes or function.  They report their findings in the open-access Nature journal, Scientific Reports ("Amylases without known homologues discovered in an acid mine drainage: significance and impact").

Amylases are enzymes that catalyze the breakdown of carbohydrates, or in the case of bacteria described here, degrade polymers found in their acidic, metal-heavy surroundings.  Amylases from bacteria that grow in culture have been well-studied, and have been classified into several families based on their structure and other characteristics.  Some have been found in extreme environments, but no one had reported the sequencing of DNA from Acid Mine Drainages before this paper.  These are very low pH, very high metal environments. 

The authors
...decided to perform a function-based screening for the well-known amylases, using standard techniques. This strategy allowed the isolation of 28 positive clones, 2 of them being subcloned, the proteins purified and characterized in vitro. In silico analyses based on the nucleotidic sequence and both the primary and the predicted tertiary structures revealed that they are completely different from other known hydrolases as both genes encode a « protein of unknown function » and display no known conserved amylolytic domain. Nevertheless, in vitro tests confirmed the amylolytic activity of these 2 enzymes.
That is, these genes did degrade polysaccharide, but neither of the subclones matched any known amylase sequences in the databases. 

As Delavat et al. point out, much is known about lab-friendly bacteria, and a whole lot less about organisms that can't be grown in the lab.  Thus, if these results are confirmed, the fact that these genes, from organisms that were found in an extreme previously unexplored environment, don't look like other known amylase sequences doesn't at all suggest that these bacteria are unique, or that they don't share the same common origin the rest of us share.  Rather, it suggests that the lab-centric biology of the last century has given us a lab-centric view of the world.  It's no surprise that bacteria that live in the low pH, high metal extremes of Acid Mine Drainages would have evolved particular enzymes appropriate for that environment.  But it's also not a surprise that these enzymes have a function that is common to bacteria in every environment.

That the genes that code for these enzymes are unlike any of the subset of amylases yet described is another example of phenogenetic drift, the conservation of a biological trait or function even when its underlying genetic basis has changed.  These genes may look novel now, but as more bacteria are characterized from non-lab environments it's likely that more will be found that share some of the characteristics of these amylase genes. 

Note, also, that these sequences are genes -- they have protein coding structures and are identifiable from sequences as such.  They are not 'random' sequences with no known relation to the usual characteristics of genes.


Anonymous said...

These amylases are merely the tip of the iceberg. Unique genes, often known as "orphans", "ORFans" or "taxomonically restricted genes" are being found in every new genome sequence. For reviews see:

Ken Weiss said...

This is a very good contribution, and thanks very much for pointing it out! It's a sign of the times, perhaps, that I subscribe to TiGs but didn't notice this in the frenzied pass-through of what's in my daily mailbox.

But this paper merits deeper consideration, in that it relates to other ideas, like Ohno's original 'evolution by gene duplication'.

Normally, that idea is so powerful that it's been hard to find truly orphan genes. I've been involved in that process, when I was skeptical about an enamel-forming gene, amelogenin, that seemed to be without a family.

As it turned out, thanks to some serendipidity and the phenomenally good work by my associate here, Kazz Kawasaki, amelogenin is part of a very old, and very important family of biomineralization-related genes.

The point there is that the nature of the protein functions coded by these genes made homology searches very difficult. But once we (i.e., Kazz) figured this out, family relationships were quickly found.

If well-established genes do exist, then where did then come from if they are not members of a wider (and older) gene family? And if they've been around a while how could they not have proliferated into a family?

I'm jumping the gun here, because I've now only looked at the abstract of this paper. But my prediction is that either there are gene families (even if taxonomically restricted, which would not be hard to explain) rather than orphan singletons, and/or there must be homologs, or else there must at least be exon homologs,....or else we have some explaining to do.