Tumorigenesis as the Paradigm of Quasi-neutral Molecular Evolution

In the absence of both positive and negative selections, coding sequences evolve at a neutral rate (R = 1). Such a high genomic rate is generally not achievable due to the prevalence of negative selection against codon substitutions. Remarkably, somatic evolution exhibits the seemingly neutral rate R ∼ 1 across normal and cancerous tissues. Nevertheless, R ∼ 1 may also mean that positive and negative selections are both strong, but equal in intensity. We refer to this regime as quasi-neutral. Indeed, individual genes in cancer cells often evolve at a much higher, or lower, rate than R ∼ 1. Here, we show that 1) quasi-neutrality is much more likely when populations are small (N