Mutational Patterns Cannot Explain Genome Composition: Are There Any Neutral Sites in the Genomes of Bacteria?

International audienceThe dissection of natural selection and neutral processes remains a core problem for molecular evolutionary biologists. One of the longest-standing controversies con- cerns the causes of genome base compo- sition, notably the variation in the sum of G and C content (GC) between 17% and 75% in bacteria. Sueoka argued very early that GC content variation is driven by mutational biases and, as this bias affects non-synonymous sites, protein evolution might also be largely driven by neutral forces [1]. Later, Muto and Osawa showed that 4-fold degenerate positions in codons exhibit the largest range of GC content (GC4), whereas the non-degener- ate second codon positions (GC2) exhibit the narrowest (Figure 1) [2]. As the footprint of genomic GC variation is most evident in those sites under the least selective constraint for amino acid com- position, it has become accepted that GC content variation is primarily driven by neutral mutational effects and has little adaptive relevance [2]