A beginners guide to estimating the non-synonymous to synonymous rate ratio of all protein-coding genes in a genome

TY - JOUR

T1 - A beginners guide to estimating the non-synonymous to synonymous rate ratio of all protein-coding genes in a genome

AU - Jeffares, Daniel C.

AU - Tomiczek, Bartłomiej

AU - Sojo, Victor

AU - dos Reis, Mario

PY - 2015

Y1 - 2015

N2 - The ratio of non-synonymous to synonymous substitutions (dN/dS) is a useful measure of the strength and mode of natural selection acting on protein-coding genes. It is widely used to study patterns of selection on protein genes on a genomic scale—from the small genomes of viruses, bacteria, and parasitic eukaryotes to the largest eukaryotic genomes. In this chapter we describe all the steps necessary to calculate the dN/dS of all the genes using at least two genomes. We include a brief discussion on assigning orthologs, and of codon-aware alignment of orthologs. We then describe how to use the CODEML program of the PAML package for phylogenetic analysis to calculate the dN/dS and how to perform some statistical tests for positive selection. We then outline some methods for interpreting output and describe how one may use this data to make discoveries about the biology of your species. Finally, as a worked example we show all the steps we used to calculate dN/dS for 3,261 orthologs from six Plasmodium species, including tests for adaptive evolution (see worked_example.pdf).

AB - The ratio of non-synonymous to synonymous substitutions (dN/dS) is a useful measure of the strength and mode of natural selection acting on protein-coding genes. It is widely used to study patterns of selection on protein genes on a genomic scale—from the small genomes of viruses, bacteria, and parasitic eukaryotes to the largest eukaryotic genomes. In this chapter we describe all the steps necessary to calculate the dN/dS of all the genes using at least two genomes. We include a brief discussion on assigning orthologs, and of codon-aware alignment of orthologs. We then describe how to use the CODEML program of the PAML package for phylogenetic analysis to calculate the dN/dS and how to perform some statistical tests for positive selection. We then outline some methods for interpreting output and describe how one may use this data to make discoveries about the biology of your species. Finally, as a worked example we show all the steps we used to calculate dN/dS for 3,261 orthologs from six Plasmodium species, including tests for adaptive evolution (see worked_example.pdf).

KW - Adaptive evolution

KW - CODEML

KW - dN/dS

KW - Evolutionary rate

KW - Malaria

KW - PAML

KW - Plasmodium

KW - Synonymous/non-synonymous rate ratio

UR - http://www.scopus.com/inward/record.url?scp=84921865077&partnerID=8YFLogxK

U2 - 10.1007/978-1-4939-1438-8_4

DO - 10.1007/978-1-4939-1438-8_4

M3 - Article

C2 - 25388108

SN - 1064-3745

VL - 1201

SP - 65

EP - 90

JO - Methods in Molecular Biology

JF - Methods in Molecular Biology

ER -