Enigmatic origin of hepatitis B virus: An ancient travelling companion or a recent encounter?

Table 1 Subgenotypes, sub-types and geographical origin of hepatitis B virus

	Subgenotype	Sub-type	Geographical origin
A	A1 (Aa, A’)	adw2, ayw1	Africa, Asia, South America
	A2 (Ae, A-A’)	adw2, ayw1	Northern Europe, North America, South Africa
	A3 (Ac)		Cameroon, Gabon, Rwanda
	A4		Mali, Gambia
	A5		Nigeria, Rwanda, Cameroon, Haiti (African pop.)
	A6		Congo, Rwanda
	A7	ayw1, adw2, ay	Cameroon, Rwanda
B	B1 (Bj)	adw2	Japan
	B2 (Ba)	adw2, adw3	Asia without Japan
	B3	adw2, ayw1	Indonesia, Philippines
	B4	ayw1, adw2	Vietnam, Cambodia
	B5		Philippines
	B6		Alaska, Northern Canada, Greenland
	B7-B9		Indonesia
C	C1 (Cs)	adrq+, ayr, adw2, ayw1	South-east Asia (Vietnam, Myanmar, Thailand, Southern China)
	C2 (Ce)	adrq+, ayr	Far East (South Korea, Japan, Northern China)
	C3	adrq–, adrq+	Pacific Islands (Micronesia, Melanesia, Polynesia)
	C4		Australia
	C5		Philippines, Vietnam
	C6		Indonesia, Philippines
	C7		Philippines
	C8-C16		Indonesia
D	D1	ayw2, adw1, ayw1	Europe, Middle East, Asia, Tunisia, Egypt
	D2	ayw3, ayw1	Europe, Morocco, India
	D3	ayw3, ayw2, ayw4	South Africa, Asia, Europe, United States, Northern Canada
	D4	ayw2, ayw3	Australia, Japan, Papua New Guinea
	D5		East India, Japan
	D6		Indonesia
	D7		Tunisia
	D8		Niger
	D9		Eastern India
E		ayw4, ayw2	Sub-Saharan Africa, United Kingdom, France, Saudi Arabia
F	F1a	adw4, ayw4	South and Central America
	F1b	adw4	Argentina, Japan, Venezuela, United States
	F2	adw4	South America (Brazil, Venezuela, Nicaragua)
	F3	adw4	Venezuela, Panama, Columbia, Bolivia
	F4	adw4	Bolivia, France, Argentina
G		adw2	United States, Germany, Japan, France, Mexico
H		adw4	United States, Japan, Nicaragua
I	I1	adw2	Laos, Vietnam, North-west China
	I2	ayw2	Laos, Vietnam
J		ayw	Japan

Table 2 Hepatitis B virus genotype substitution rates estimated using different methods

Genotype	Evolutionary rate	95%HPD	TMRCA	95%HPD	Ref.
A	0.90 × 10-4	0.12 × 10-4-1.7 × 10-4	237	29-455	[43]
	8.6 × 10-4	4.3 × 10-4-14.3 × 10-4			[106]
A2	0.91 × 10-4	0.11 × 10-4-1.7 × 10-4	62	12-112	[43]
A2	3.23 × 10-5	5.6 × 10-8-9.0 × 10-5			[71]
	2.72 × 10-4	1.73 × 10-4-5.8 × 10-4			[48]
C	2 × 10-4	5.4 × 10-4-3.61 × 10-4			[106]
	3.73 × 10-4		96	23-271	[107]
D	6.3 × 10-4	4.8 × 10-4-7.8 × 10-4	84	55-110	[49]
	4.4 × 10-4	2.6 × 10-4-6.2 × 10-4	128	66-210	[49]
	1.21 × 10-4	1.83 × 10-4-2.27 × 10-4			[106]
	4.30 × 10-4	1.16 × 10-4-7.26 × 10-4	66	26-140	[107]
	3.67 × 10-4	2.8 × 10-4-4.5 × 10-4	85	67-103	[43]
D3	3.29 × 10-4	2.9 × 10-4-3.7 × 10-4	70	61-79	[43]
	5.4 × 10-5	4.0 × 10-5-7.21 × 10-5	104	139-79	[42]
D1	4.2 × 10-4	3 × 10-4-6.6 × 10-4	46	20-67	[48]
E	9.29 × 10-4	0.18 × 10-4-20.2 × 10-4			[106]
	2.4 × 10-4	0.55 × 10-4-5.54 × 10-4	58	40-83	[81]
	3.2 × 10-4	2.2 × 10-4-4.5 × 10-4	29.6	16-52	[75]
F	1.67 × 10-4	0.94 × 10-4-2.37 × 10-4	284	120-501	[86]
	1.67 × 10-4	0.94 × 10-4-2.37 × 10-4	255	224-282	[89]
	2.60 × 10-4-1.5 × 10-5			150.9-2418.4	[87]
Root	7.7 × 10-4	0.84 × 10-4-8.61 × 10-4	229	64-580	[107]
	2.2 × 10-6	1.5 × 10-6-3 × 10-6	33600	22000-47000	[94]

Evolutionary rates are expressed as mean substitutions/site per year (s/s per year), with confidence intervals as 95%HPD. The times of the most recent common ancestor (tMRCA) are also indicated with confidence limits.