Studying metabolic horizontal gene transfer through ancestral state reconstruction and flux balance analysis

Pang and Lercher. 2019. Each of 3,323 metabolic innovations in the evolution of E. coli arose through the horizontal transfer of a single DNA segment. PNAS USA

Summarized from DalMUG group discussion and written by: Gavin Douglas


Bacteria are known to commonly exchange genetic material through horizontal gene transfer (HGT; also known as lateral gene transfer) that enables them to adapt to novel environments. These adaptations often involve a gain or shift in a metabolic trait (e.g. the ability to metabolize a different sugar). There are many exciting questions in this area, but one pertinent one is how are complex traits, those dependent on a large number of genes, transferred by HGT? There are three clear possibilities: complex traits are (1) transferred by single large events, (2) by multiple non-complex neutral events, or (3) by stepwise non-complex events with incremental increases in fitness. Pang and Lercher took a bioinformatics approach to investigate these possibilities across intestinal strains of E. coli.

Points of Interest

  • Clear description of the immense metabolic diversity across E. coli strains.

  • Used GLOOME to infer the patterns of gene gain and loss across the strain lineages.

  • Besides strains that are nearly identical, phenotypic similarity was independent of amino acid sequence divergence (which contrasts with the trend at longer timescales).

  • Interesting way to compute all possible metabolic pathways - simply combine all of the networks together and compute a super-metabolic network.

  • Based on the theoretically possible transfers - only 2.4% of new phenotypes and 7.4% of yield improvements required the acquisition of multiple DNA segments (i.e. more than 30 kb separated the required genes).

  • Of the 3,323 actual transfers inferred all involved genes within 30 kb of each other (even the <3% that required more than 5 relevant genes)

  • Importantly 10-20% of new phenotypes required a pre-existing transfer event (i.e. an adaptive stepping stone, which is consistent with explanation #3 above).

Points of Confusion

  • Why restrict the analysis to ~50 strains when so many others are available?

  • Are different mechanisms of HGT more or less compatible with the upper transfer limit of 30 kb?

  • The italicized sentence from the paper below is very interesting, but we’re not totally sure how to interpret it - does it mean that intermediate transfers of a complex trait also always occurred in the same genomic region?

Note that every single one of these apparently complex phenotypic innovations could instead have been bestowed on the immediate ancestor of the successive DNA acquisitions through a single <30-kb DNA segment presently found in one of the other extant E. coli strains.

  • A clearer breakdown of what the simulated environments consisted of would have been useful to better evaluate the methods.
Written on July 29, 2019