pone.0018348.g001.png

Maximum parsimony tree of 45 entire mtDNA genomes of patients

suffering Ras/MAPK pathway syndromes.

The mutations are displayed along branches; the variant nomenclature is

refered to was taken from the rCRS [30]. All mutations are

transitions unless a suffix specifies a transversion (A, C, G, T), a

deletion (d), an insertion (+), a synonymous substitution

(s), a mutational change in tRNA

(-t), a mutational change in rRNA

(-r), stop codon (-stp),

non-coding variant located in the mtDNA coding region

(-nc) or amino acid replacement (indicated in round

brackets). Recurrent mutational events are underlined. A prefix

indicates a back mutation (@) or a position that is located in an

overlapping region shared by two genes (*). Several mutational

hotspot variants were not considered for phylogenetic reconstruction and

therefore were eliminated from the tree; these included variants at the

homopolymeric tracks around position 310, the microsatellite at

m.523–524 d (aka m.522–523 d), the transversion

m.16182A>C, m.16183A>C, m.16193+1C(C), m.16519T>C, and

length or point heteroplasmies. Codes of the samples are indicated in

colored circles at the terminal branches of the phylogeny: green

indicates a mutation on gene SOS1, orange indicates a

mutation on PTPN11, yellow indicates a mutation on

KRAS, grey indicates lack of mutations on genes

SOS1, PTPN11,

KRAS, and RAF, and white indicates

that data is not available for that sample.

Done