Genetic diversities of MT-ND3 and MT-ND4L genes are associated with high-altitude adaptation

Figures & data

Figure 1. Median-joining network of MT-ND3 (A) and MT-ND4L (B) haplotypes. Black sector in H1 and Ha1 represents Tibetan cattle and Tibetan yak. In other haplotypes, black sector only represents Tibetan cattle. White sector represents Holstein-Friesian Cattle. The arrow indicates that the reference sequence belongs to haplotype H1 and Ha1.

Figure 2. Diagram of the transmembrane structure of the MT-ND3 (A) and MT-ND4L (B) protein predicted using the SMART programme. The arrows indicate that the non-synonymous mutations were present in each of the transmembrane regions.

Table 1. Percentage of nucleotide composition of MT-ND3 and MT-ND4L gene sequences in Tibetan yaks (TY), Tibetan cattle (TC), and Holstein-Friesian (HF) populations.

Gene	Population	Number of samples	T％	C％	A％	G％	T + A％
ND3	TY	51	28.0	28.9	30.9	12.1	58.9
	TC	59	27.4	29.8	30.4	12.4	57.8
	HF	60	27.2	30.1	30.4	12.3	57.6
ND4L	TY	51	33.0	23.2	32.0	11.8	65.0
	TC	59	32.0	24.2	32.2	11.6	64.2
	HF	60	31.7	24.5	32.1	11.7	63.8

Table 2. Mutations in MT-ND3 of Tibetan cattle (TC) and Holstein-Friesian (HF).

Sites	Variants	MN^a		TMN^b	p-Value^c	OR^d	95% CI^e
		TC	HF
9893	A→G	7	22	29	.03576*	0.39369	0.16680–0.92923
9908	T→C	0	4	4	.13256	–	–
9911	A→G	0	4	4	.13256	–	–
9914	T→C	0	2	2	.50636	–	–
9923	G→A	45	59	104	.91756	0.96051	0.63938–1.443
9929	T→C	45	59	104	.91756	0.96051	0.63938–1.443
9932	A→C	7	22	29	.03576*	0.39369	0.16680–0.92923
9947	C→T	45	59	104	.91756	0.96051	0.63938–1.443
9980	C→T	38	37	75	.27890	1.323	0.82775–2.114
9995	A→G	45	59	104	.91756	0.96051	0.63938–1.443
10004	T→C	45	59	104	.91756	0.96051	0.63938–1.443
10022	T→C	45	59	104	.91756	0.96051	0.63938–1.443
10041	T→C	38	37	75	.27890	1.286	0.80488–2.055
10049	A→G	45	59	104	.91756	0.96051	0.63938–1.443
10073	C→T	43	10	53	2.126E-08**	5.853	2.910–11.769
10155	C→T	7	22	29	.03576*	0.39369	0.16680–0.92923
10157	G→A	45	59	104	.91756	0.96051	0.63938–1.443

MN^a: mutation number. TMN^b: total mutation number. p-Value^c: *p < .003 and **p < .0006 (0.05/17 = .003, 0.01/17 = .0006). OR^d: odds ratio. 95% CI^e: 95% confidence interval. Ter：termination codon. Only missense mutations were considered here.

Table 3. Mutations in MT-ND4L of Tibetan cattle (TC) and Holstein-Friesian (HF).

Sites	Variants	MN^b		TMN^b	p-Value^c	OR^d	95% CI^e
		TC	HF
10253	C→T	45	59	104	.82893	1.059	0.69343–1.616
10255	T→C	45	59	104	.82893	1.059	0.69343-–1.616
10270	A→G	7	22	29	.05395	0.42306	0.17812-–1.005
10277	G→A	45	59	104	.82893	1.059	0.69343-–1.616
10349	A→G	0	3	3	.26762	–	–
10392	C→T	0	2	2	.51175	–	–
10507	G→A	45	59	104	.82893	1.059	0.69343-–1.616
10516	T→C	45	59	104	.82893	1.059	0.69343–1.616
10523	C→A	45	59	104	.82893	1.059	0.69343–1.616

MN^a: mutation number. TMN^b: total mutation number. p-Value^c: *p < .006 and **p < .0011 (0.05/9 = .006, 0.01/9 = .0011). OR^d: odds ratio. 95% CI^e: 95% confidence interval. Only missense mutations were considered here.

Table 4. Haplotype distribution for MT- ND3 in Holstein-Friesian (HF) and Tibetan cattle (TC).

Haplotype	Number of HF	Number of TC	p-Value^a	Odds Ratio	95% CI
H1（RS）	1	14	.00022*	0.05448	0.00691–0.42982
H2	4	5	.74301	0.77143	0.19663–3.026
H3	18	2	.00012**	12.214	2.687–55.529
H4	4	0	.11872	–	–
H5	0	10	.00059**	–	–
H6	2	0	.49580	–	–
H7	31	28	.71514	1.183	0.57642–2.430

p-value^a Two-tailed Fisher’s exact test with Bonferroni correction: *p < .0071 and **p < .0014 (0.05/7 = .0071, 0.01/7 = .0014).

Table 5. Haplotype distribution for MT-ND4L in Holstein-Friesian (HF) cattle and Tibetan cattle (TC).

Haplotype	Number of HF	Number of TC	p-Value^a	Odds Ratio	95% CI
Ha1（RS）	1	14	.00022*	0.05448	0.00691–0.42982
Ha2	2	0	.49580	–	–
Ha3	20	4	.00043*	6.875	2.181–21.674
Ha4	34	38	.45461	0.72267	0.34546–1.512
Ha5	3	0	.24370	–	–
Ha6	0	3	.11872	–	–

p-value^a Two-tailed Fisher’s exact test with Bonferroni correction: *p < .0083 and **p < .0017 (0.05/6 = .0083 0.01/7 = .0017).