Supplementary Data for the Manuscript Entitled

Supplementary Data for the manuscript entitled,

A Mantel test and general linear model based approach for inferring selection to climate

Srilakshmi M. Raj, Luca Pagani, Irene Gallego Romero, Toomas Kivisild, William Amos

Supplementary Figures and Tables

Figure S1. The number of genic windows showing P <= 10-4 (blue) or

<= 10-5 (red) in more than 1,2 3 or 4 climate combinations…………………………………..2

Figure S2. Regression line between the –log10P obtained

using the full dataset run on 2*106 randomizations (Ptrue) and the same run

masking half of the dataset each time (Phalves)………………………………………………...2

Figure S3. Inference of directional and balancing selection

associated with climate…………………………………………………………………………3

Table S1. Climate variables assigned to the 45 populations

used in this study………………………………………………………………………………..4

Table S2. Correlation of MAGIC hits by climate variables……………….5

Table S3. All the genic windows yielding a hit ( -log10P >=5)

in the present study……………………………………………………………………………..7

Supplementary Figures

Figure S1. The number of genic windows showing P <= 10-4 (blue) or <= 10-5 (red) in more than 1,2 3 or 4 climate combinations.

Figure S2. Regression line between the –log10P obtained using the full dataset run on 2*106 randomizations (Ptrue) and the same run masking half of the dataset each time (Phalves). The displayed equation was used to infer the Ptrue=0 after 2 * 106 randomizations.

Figure S3. Inference of directional and balancing selection associated with climate. At any given locus, the slope of the relationship between heterozygosity and distance from Africa provides an indication of the nature of selection: neutral loci on average have negative slopes while those under balancing selection have zero or even slightly positive slopes while those under directional selection may have more extreme negative slopes. We plotted the frequency distribution of slopes for our hits (P<10-5, white bars) relative to the underlying distribution of slopes observed for all non-hit genes, indicated by the dotted line. Filled circles denote the frequency of non-hit genes at a given bin. Significance of excesses and deficits in each slope bin are obtained with a simple chi-squared test. Those bins that met significance are identified by asterisks: * denotes P>0.05, ** denotes P>0.01. While individual bin significance is achieved only among the most negative slopes, it is clear that our hits generally show an excess of 'neutral' slopes and a strong overall excess of strongly negative slope. Our two top hits, ADRA2A and ADRA2C both have slopes near zero, indicating balancing selection.

Supplementary Tables

Table S1. Climate variables assigned to the 45 populations used in this study.

Winter / Summer
Continent / Map Number / Population / N / long / lat / T / Sr / Pr / rH / T / Sr / Pr / rH
1. Europe and Altai
1 / Orcadians / 15 / -9.65 / 60 / 5.7 / -35.1 / 10.5 / 80.9 / 12.4 / -118.5 / 19.8 / 86.4
2 / Spanish / 12 / -7.15 / 37.5 / 10.6 / -113.5 / 13.1 / 76.3 / 24.8 / -204.0 / 20.9 / 48.2
3 / French / 28 / 2.5 / 45 / 4.4 / -82.1 / 10.7 / 88.1 / 18.4 / -178.3 / 21.9 / 69.7
4 / Italians / 19 / 10 / 45 / 2.7 / -83.6 / 8.1 / 81.4 / 17.6 / -168.7 / 20.7 / 76.6
5 / Lithuanians / 10 / 22.5 / 55 / -1.4 / -35.9 / 8.5 / 89.7 / 16.2 / -116.3 / 22.6 / 78.9
6 / Romanians / 16 / 25 / 45 / -1.3 / -71.5 / 8.7 / 86.3 / 17.7 / -162.9 / 22.8 / 74.7
7 / Belorussians / 10 / 27.5 / 55 / -4.6 / -31.2 / 7.7 / 89.2 / 15.7 / -107.3 / 22.2 / 77.3
8 / Turks / 19 / 32.5 / 40 / -1.4 / -78.8 / 7.0 / 77.3 / 17.7 / -164.1 / 16.2 / 55.6
9 / Adygei / 17 / 40 / 45 / 2.3 / -74.2 / 10.3 / 87.1 / 21.5 / -170.7 / 25.4 / 66.5
10 / Mordovians / 15 / 45 / 55 / -7.9 / -28.1 / 6.7 / 89.2 / 16.2 / -113.2 / 22.6 / 76.0
11 / Armenians / 16 / 45 / 40 / -5.3 / -65.8 / 5.2 / 85.3 / 16.0 / -157.4 / 16.4 / 63.8
12 / Chuvashs / 17 / 47.5 / 55 / -8.7 / -29.9 / 6.5 / 89.1 / 16.6 / -117.6 / 22.5 / 73.0
13 / Turkmens / 15 / 57.5 / 37.5 / 3.1 / -88.4 / 7.8 / 55.4 / 25.7 / -177.4 / 13.7 / 17.7
14 / Altaians / 13 / 85 / 50 / -14.2 / -42.3 / 2.8 / 82.1 / 10.9 / -151.1 / 13.0 / 71.1
2. Middle East and North Africa
15 / Mozabites / 27 / 2.5 / 32.5 / 11.7 / -99.9 / 9.9 / 44.5 / 30.8 / -151.6 / 17.9 / 17.7
16 / Egyptians / 12 / 30 / 30 / 14.6 / -128.0 / 13.0 / 61.6 / 26.3 / -196.0 / 19.4 / 60.6
17 / Palestinians / 46 / 35 / 32.5 / 13.1 / -94.5 / 12.8 / 71.1 / 24.5 / -155.3 / 20.9 / 76.4
18 / Syrians / 16 / 37.5 / 35 / 9.0 / -130.1 / 11.2 / 72.5 / 27.4 / -248.1 / 20.5 / 47.5
19 / Jordanians / 20 / 37.5 / 30 / 10.4 / -121.0 / 9.1 / 45.0 / 27.1 / -182.8 / 16.7 / 35.3
20 / Saudis / 20 / 45 / 25 / 16.5 / -124.8 / 14.6 / 37.1 / 34.2 / -189.3 / 16.6 / 12.7
21 / Iranians / 20 / 50 / 35 / -0.7 / -94.5 / 4.7 / 68.7 / 21.0 / -194.8 / 12.7 / 35.1
3. Central and South Asia
22 / Balochi / 24 / 67.5 / 30 / 11.3 / -119.7 / 9.2 / 36.3 / 28.8 / -170.8 / 21.6 / 28.7
23 / Tajiks / 15 / 70 / 40 / -2.0 / -55.8 / 7.0 / 90.4 / 17.3 / -154.4 / 10.9 / 34.7
24 / Gujaratis / 88 / 72.5 / 22.5 / 23.8 / -148.5 / 13.6 / 28.7 / 26.2 / -130.9 / 47.4 / 82.9
25 / Burusho / 25 / 75 / 37.5 / -13.8 / -72.3 / 1.4 / 55.7 / 3.8 / -154.6 / 5.5 / 62.3
26 / South Indians / 19 / 77.5 / 12.5 / 24.5 / -183.9 / 23.5 / 55.3 / 22.7 / -155.0 / 40.8 / 84.2
4. East Asia
27 / Uygurs / 10 / 80 / 45 / -4.9 / -50.6 / 6.0 / 84.6 / 17.1 / -149.3 / 15.0 / 45.7
28 / Tuvinians / 16 / 92.5 / 52.5 / -13.1 / -39.9 / 4.1 / 89.3 / 11.3 / -145.4 / 17.3 / 90.6
29 / Burmese / 15 / 95 / 22.5 / 19.3 / -139.6 / 13.8 / 34.2 / 23.0 / -114.7 / 45.9 / 93.5
30 / Tu / 10 / 100 / 35 / -11.6 / -108.6 / 2.6 / 72.4 / 7.3 / -188.1 / 11.8 / 78.4
31 / Nganassans / 15 / 102.5 / 75 / -27.1 / -4.2 / 2.5 / 76.6 / 3.4 / -73.6 / 13.7 / 90.3
32 / Cambodians / 10 / 105 / 12.5 / 26.9 / -155.0 / 38.2 / 61.1 / 25.1 / -135.4 / 51.2 / 93.9
33 / Evenkis / 16 / 107.5 / 55 / -17.1 / -27.9 / 2.9 / 82.6 / 12.5 / -120.8 / 18.4 / 79.6
34 / Mongolians / 9 / 110 / 45 / -12.3 / -65.5 / 3.2 / 78.2 / 19.9 / -147.5 / 17.1 / 38.0
35 / Han / 44 / 115 / 32.5 / 5.6 / -99.1 / 13.3 / 74.0 / 24.7 / -117.1 / 47.1 / 89.2
36 / Oroqens / 9 / 127.5 / 50 / -15.4 / -44.1 / 3.2 / 85.2 / 16.8 / -155.2 / 25.1 / 82.2
37 / Yakuts / 25 / 130 / 62.5 / -26.9 / -22.5 / 2.2 / 89.7 / 12.9 / -123.8 / 18.9 / 76.8
38 / Japanese / 28 / 137.5 / 37.5 / 1.2 / -111.1 / 7.1 / 80.7 / 21.5 / -160.2 / 35.8 / 87.4
39 / Koryaks / 18 / 160 / 57.5 / -10.3 / -24.9 / 4.3 / 90.5 / 10.3 / -123.9 / 18.9 / 88.4
5. Oceania
40 / Papuans / 17 / 142.5 / -5 / 21.8 / -175.1 / 36.9 / 91.6 / 22.1 / -188.9 / 39.3 / 94.0
41 / Melanesians / 11 / 155 / -5 / 27.0 / -128.9 / 45.0 / 80.7 / 27.9 / -146.9 / 48.9 / 78.4
6. Native Americans
42 / Pima / 14 / 252.5 / 30 / 10.7 / -119.2 / 7.2 / 36.4 / 23.4 / -143.1 / 25.3 / 53.9
43 / Mayas / 21 / 270 / 20 / 24.2 / -152.4 / 30.7 / 76.7 / 27.7 / -174.2 / 43.5 / 81.2
44 / Colombians / 7 / 292.5 / 2.5 / 23.6 / -145.1 / 44.7 / 95.4 / 23.7 / -151.1 / 41.9 / 92.5
45 / Karitiana / 13 / 297.5 / -10 / 25.5 / -122.1 / 36.6 / 71.6 / 24.1 / -119.2 / 46.9 / 95.6

The four climate variables we used are: (1) T, air temperature (measured in ºC), (2) Pr, precipitation rate (kg/m2/s), (3) rH, relative humidity (%), and (4) Sr, solar radiation (W/m2). The data source we use reports data in terms of monthly averages across ~40 years of the collection, from the NCEP/NCAR database: ftp://ftp.cdc.noaa.gov/Datasets/ncep.reanalysis/ (Kistler et al. 2001).

Kistler, R., E. Kalnay, W. Collins, S. Saha, G. White et al., 2001 The NCEP-NCAR 50-Year Reanalysis: Monthly Means CD-ROM and Documentation. Bulletin of the American Meteorological Society 82: 247-268.

Table S2. Spearman rank correlation of MAGIC hits by climate variables.

Ts / Tw / Srs / Srw / Prs / Prw / rHs / rHw
Ts / 1 / 0.64 / 0.19 / 0.51 / 0.22 / 0.26 / 0.15 / 0.25
Tw / 0.64 / 1 / 0.08 / 0.76 / 0.5 / 0.64 / 0 / 0.19
Srs / 0.19 / 0.08 / 1 / 0.25 / 0.04 / 0 / 0.25 / 0.02
Srw / 0.51 / 0.76 / 0.25 / 1 / 0.38 / 0.46 / 0 / 0.28
Prs / 0.22 / 0.5 / 0.04 / 0.38 / 1 / 0.61 / 0.31 / 0.02
Prw / 0.26 / 0.64 / 0 / 0.46 / 0.61 / 1 / 0.1 / 0
rHs / 0.15 / 0 / 0.25 / 0 / 0.31 / 0.1 / 1 / 0.16
rHw / 0.25 / 0.19 / 0.02 / 0.28 / 0.02 / 0 / 0.16 / 1

Tw - Winter temperature

Ts - Summer temperature

Prw - Winter precipitation

Prs - Summer precipitation

rHw - Winter relative humidity

rHs - Summer relative humidity

Srw - Winter solar radiation

Srs - Summer solar radiation

1

Table S3. All the genic windows yielding a hit ( -log10P >=5) in the present study.

-log10(P-split)
2*106 rand. / Extrapolated
-log10(P) / ENSEMBL
GENE ID / HUGO GENE ID / Climate / Season / Continent Scrambling / Europe and Altai
p-value / Middle East and North Africa / Central and South Asia / East Asia / Oceania / Americas / Slope of Heterozygosity /Geographic Distance from Addis Ababa / Correlation Coefficient of Heterozygosity/
Geographic Distance from Addis Ababa
5.52 / 10.10 / ENSG00000150594 / ADRA2A / Sr / Winter / 0 / 2.50E-01 / 2.10E-01 / 1.50E-02 / 7.90E-03 / 0.50 / 0.81 / 0.17 / 0.01
4.92 / 8.90 / ENSG00000184160 / ADRA2C / T / Winter / 0 / 4.67E-02 / 2.10E-01 / 4.94E-03 / 5.93E-03 / 0.51 / 0.16 / 2.65 / 0.20
4.77 / 8.60 / ENSG00000207207 / #NA# / Sr / Winter / 0 / 3.80E-01 / 2.80E-01 / 2.91E-02 / 2.80E-05 / 0.53 / 0.83 / -9.42 / -0.54
4.77 / 8.60 / ENSG00000213247 / #NA# / Sr / Winter / 0 / 1.00E-01 / 2.20E-01 / 7.55E-03 / 6.46E-04 / 0.45 / 0.96 / 2.03 / 0.16
4.62 / 8.30 / ENSG00000213247 / #NA# / Pr / Winter / 0 / 4.46E-02 / 1.00E-01 / 4.90E-02 / 6.61E-03 / 1.00 / 0.63 / 2.03 / 0.16
4.55 / 8.17 / ENSG00000070886 / EPHA8 / Sr / Winter / 0 / 4.42E-02 / 6.90E-01 / 1.20E-01 / 1.61E-03 / 1.00 / 0.26 / -0.82 / -0.05
4.54 / 8.14 / ENSG00000209656 / #NA# / Sr / Winter / 0 / 4.87E-03 / 1.40E-01 / 5.10E-01 / 3.59E-04 / 1.00 / 0.81 / 2.06 / 0.09
4.52 / 8.11 / ENSG00000186329 / TMEM212 / rH / Summer / 0 / 1.02E-02 / 6.20E-01 / 6.00E-02 / 7.61E-03 / 0.42 / 0.19 / -10.61 / -0.73
4.49 / 8.05 / ENSG00000216328 / #NA# / rH / Winter / 0 / 9.00E-02 / 4.20E-01 / 7.00E-02 / 4.24E-02 / 0.54 / 0.54 / 1.55 / 0.09
4.46 / 7.97 / ENSG00000077514 / POLD3 / Sr / Winter / 0 / 2.20E-01 / 5.30E-01 / 8.36E-03 / 6.03E-04 / 0.44 / 0.61 / -2.39 / -0.18
4.46 / 7.97 / ENSG00000205243 / #NA# / Sr / Winter / 0 / 2.52E-03 / 1.32E-02 / 1.10E-01 / 4.90E-04 / 1.00 / 0.07 / -1.05 / -0.09
4.44 / 7.95 / ENSG00000060138 / CSDA / Pr / Summer / 0 / 9.90E-01 / 5.80E-01 / 8.00E-02 / 7.78E-04 / 1.00 / 0.04 / 7.87 / 0.51
4.39 / 7.84 / ENSG00000115738 / ID2 / rH / Summer / 0 / 7.31E-03 / 1.40E-01 / 8.00E-02 / 1.50E-01 / 0.50 / 0.22 / -10.10 / -0.58
4.36 / 7.78 / ENSG00000209656 / #NA# / T / Summer / 0 / 1.00E-01 / 1.50E-01 / 6.00E-01 / 4.95E-02 / 0.49 / 0.83 / 2.06 / 0.09
4.34 / 7.74 / ENSG00000163281 / GNPDA2 / Pr / Summer / 0 / 4.20E-01 / 6.10E-01 / 6.80E-01 / 1.14E-03 / 0.48 / 0.58 / 17.56 / 0.71
4.31 / 7.68 / ENSG00000198669 / #NA# / Pr / Summer / 0 / 4.40E-01 / 4.90E-01 / 2.10E-01 / 9.01E-03 / 1.00 / 0.32 / -18.85 / -0.69
4.23 / 7.52 / ENSG00000144476 / CXCR7 / rH / Summer / 0 / 1.00E-01 / 9.00E-02 / 6.00E-02 / 1.20E-01 / 1.00 / 0.56 / -12.53 / -0.60
4.22 / 7.51 / ENSG00000139263 / LRIG3 / Pr / Winter / 0 / 1.00E+00 / 8.00E-01 / 2.20E-01 / 1.81E-02 / 0.47 / 0.04 / 2.77 / 0.23
4.22 / 7.51 / ENSG00000129347 / KRI1 / Pr / Summer / 0 / 8.53E-04 / 6.80E-01 / 1.50E-01 / 4.78E-04 / 0.50 / 0.19 / -8.73 / -0.53
4.21 / 7.48 / ENSG00000092470 / WDR76 / rH / Summer / 0 / 6.57E-04 / 3.10E-01 / 9.00E-02 / 3.22E-03 / 1.00 / 0.81 / -21.14 / -0.72
4.20 / 7.46 / ENSG00000075891 / PAX2 / rH / Summer / 0 / 2.70E-01 / 1.70E-01 / 8.00E-02 / 3.88E-04 / 1.00 / 0.92 / -20.24 / -0.65
4.20 / 7.46 / ENSG00000171877 / FRMD5 / rH / Summer / 0 / 1.63E-03 / 4.20E-01 / 4.80E-01 / 6.00E-02 / 1.00 / 0.27 / -14.41 / -0.63
4.19 / 7.45 / ENSG00000152292 / SH2D6 / Sr / Winter / 0 / 2.10E-01 / 2.50E-01 / 5.00E-02 / 2.26E-04 / 0.47 / 0.81 / -9.60 / -0.57
4.19 / 7.45 / ENSG00000221947 / XKR9 / Pr / Summer / 0 / 6.00E-01 / 5.40E-01 / 2.20E-01 / 4.84E-03 / 1.00 / 0.34 / -19.18 / -0.69
4.17 / 7.41 / ENSG00000199452 / #NA# / rH / Summer / 0 / 4.24E-02 / 5.00E-02 / 2.00E-01 / 1.20E-01 / 0.59 / 0.09 / -13.39 / -0.57
4.14 / 7.35 / ENSG00000206974 / #NA# / rH / Winter / 0 / 6.00E-02 / 3.70E-01 / 7.00E-02 / 7.00E-02 / 0.55 / 0.49 / 2.82 / 0.17
4.14 / 7.34 / ENSG00000208922 / #NA# / rH / Winter / 0 / 1.20E-01 / 5.20E-01 / 7.00E-02 / 8.00E-02 / 0.44 / 0.45 / -0.10 / -0.01
4.09 / 7.24 / ENSG00000214192 / UBE2V1P2 / rH / Summer / 0 / 6.94E-03 / 9.00E-02 / 4.50E-01 / 1.94E-02 / 1.00 / 0.25 / -12.28 / -0.55
4.03 / 7.12 / ENSG00000112335 / SNX3 / rH / Winter / 0 / 7.00E-02 / 4.30E-01 / 5.00E-02 / 1.10E-01 / 0.47 / 0.46 / 1.29 / 0.08
4.01 / 7.09 / ENSG00000201416 / SNORA71B / rH / Summer / 0 / 1.67E-02 / 2.84E-02 / 2.90E-01 / 5.00E-02 / 0.40 / 0.09 / -12.76 / -0.62
3.97 / 7.01 / ENSG00000031081 / ARHGAP31 / Sr / Winter / 0 / 3.50E-01 / 4.40E-01 / 3.33E-02 / 3.17E-03 / 0.46 / 0.20 / -0.34 / -0.03
3.93 / 6.92 / ENSG00000198284 / NUP210P1 / Pr / Summer / 0 / 1.80E-01 / 1.37E-02 / 5.00E-02 / 4.30E-03 / 1.00 / 0.08 / 1.24 / 0.10
3.92 / 6.90 / ENSG00000144802 / NFKBIZ / Sr / Winter / 0 / 1.18E-02 / 7.00E-02 / 2.40E-01 / 1.58E-02 / 1.00 / 0.34 / -6.88 / -0.49
3.91 / 6.89 / ENSG00000168781 / PPIP5K1 / rH / Summer / 0 / 3.17E-03 / 1.60E-01 / 5.70E-03 / 5.00E-02 / 1.00 / 0.50 / -15.41 / -0.59
3.90 / 6.87 / ENSG00000196564 / #NA# / rH / Summer / 0 / 5.98E-04 / 3.40E-01 / 8.00E-02 / 9.65E-03 / 1.00 / 0.31 / -16.73 / -0.69
3.89 / 6.85 / ENSG00000146233 / CYP39A1 / Sr / Winter / 0 / 4.72E-03 / 7.90E-01 / 2.20E-01 / 1.90E-01 / 0.51 / 0.57 / -3.84 / -0.31