Paul Higgs - Research Topics

Evolution of Bacterial Genomes and Horizontal Gene Transfer

1. Collins RE, Higgs PG (2012) Testing the Infinitely Many Genes model for the evolution of the bacterial core genome and pangenome. Mol. Biol. Evol. http://dx.doi.org/10.1093/molbev/mss163
2. Collins RE, Merz H, Higgs PG (2011) Origin and evolution of gene families in Bacteria and Archaea. Bioinformatics 12(Suppl 9):S14.
3. Vogan AA, Higgs PG (2011) The advantages and disadvantages of Horizontal Gene Transfer and the emergence of the first species. Biol. Direct. 6:1

Who is who?

Eric Collins Now faculty member at University of Alaska, Fairbanks.	Seyed Ali Reza Zamani Dahaj current graduate student	Paul Higgs

Core Genomes and Pangenomes

Bacteria gain and lose genes surprisingly rapidly. Even genomes that belong nominally to the same species do not have the same set of genes. In this example (from Collins and Higgs [1]) all the genes from the genomes of 14 strains of Streptococcus pneumoniae were clustered according to sequence similarity.

The Pangenome is the set of genes found at least once in a set of genomes. G_pan(n) is the number of gene families found after n genomes are included. There are about 1800 genes in each genome, but a total of more than 5000 genes in the pangenome of 14 strains. The pangenome size continues to increase each time a new genome is added because each new genome contains genes not seen previously. The Core Genome is the set of genes found on every genome in the set. G_core(n) falls to only 1200 after including all 14 genomes.

The gene frequency spectrum, G(k), is the number of gene families that are present in k genomes. This has a U-shape distribution with some core genes found in all 14 genomes and a large number of genes found in only 1 or 2 genomes. These latter genes have probably originated very recently, either by sequence evolution within the genome or Horizontal Gene Transfer from outside the group.

Horizontal Gene Transfer and Phylogenetic Trees

The phylogenetic tree of bacteria from the class Bacilli is shown below, calculated using conserved genes found in all Bacilli. The Streptococcus genomes considered above are a very closely related subgroup within this tree.

The fact that many genes are inserted and deleted on the timescale of divergence between the Strep. pneumoniae strains suggests that horizontal transfer can be very rapid. It is sometimes claimed that horizontal transfer is so frequent that it is not possible to draw phylogenetic trees for bacteria. However, there are substantial numbers of genes that are conserved over long periods of time, and reliable trees can be inferred from these genes. In our view, a strong signal of treelike evolution (vertical inheritance of genes) remains, despite the presence of substantial horizontal transfer.

Current objectives

• Develop quantitative models of genome evolution that account for rapid gain and loss of dispensable genes at the same time as slow evolution of conserved genes.
• Develop a quantitative interpretation of the presence of 'signature genes' that are specific to many groups of bacteria (see the work of Dr Radhey Gupta)
• Using maximum likelihood methods, estimate what proportion of genes is best explained by a model that permits horizontal transfer rather than a model that allows only vertical inheritance.
• Estimate the diversity of the pool of genes from which horizontally transferred genes arise.
• Consider the selective effects that would lead to increase or decrease in the frequency of horizontal transfer over time (see Vogan and Higgs [3]).