Selection in Overlapping Genes 35. de Groot S, Mailund T, Lunter G, Hein J (2008) Investigating selection on viruses: a statistical alignment approach. BMC Bioinformatics 9: 304. 36. Pedersen AM, Jensen JL (2001) A dependent-rates model and an MCMC-based methodology for the maximum-likelihood analysis of sequences with overlapping reading frames. Mol Biol Evol 18: 763–776. 37. Goldman N, Yang Z (1994) A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11: 725–736. 38. Yang Z (2006) Computational Molecular Evolution. Oxford Oxfordshire: Oxford University Press. 39. Yang Z, Nielsen R, Hasegawa M (1998) Models of amino acid substitution and applications to mitochondrial protein evolution. Mol Biol Evol 15: 1600–1611. 40. Yang Z, Nielsen R (1998) Synonymous and nonsynonymous rate variation in nuclear genes of mammals. J Mol Evol 46: 409–418. 41. Zhang J, Nielsen R, Yang Z (2005) Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level. Mol Biol Evol 22: 2472–2479. 42. Nielsen R, Yang Z (1998) Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 148: 929–936. 43. Bao Y, Bolotov P, Dernovoy D, Kiryutin B, Zaslavsky L, et al. (2008) The influenza virus resource at the National Center for Biotechnology Information. J Virol 82: 596–601. 44. Needleman SB, Wunsch CD (1970) A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol 48: 443–453. 45. Belshaw R, Pybus OG, Rambaut A (2007) The evolution of genome compression and genomic novelty in RNA viruses. Genome Res 17: 1496–1504. PLoS ONE | www.plosone.org 7 December 2008 | Volume 3 | Issue 12 | e3996