M167 aka SRY2627 R1b1c6 subclade

John McEwan

5^th November 2005 (updated 3^rd Dec 2005)

This page consists of working notes

M167 is a SNP that defines the R1b1c6 subclade. This is a rare variant within R1b, and is often considered localized to the Iberian peninsula. This page attempts to summarize what is known about this variant from the limited data available.

Frequencies of M167+

This marker SRY2627 was used by Rosser et al. (2000) in a wide variety of populations and defined as HG 22. Another marker, SRY-1532 was used to define R1a defined as HG 3 (note this marker is known for back mutation in other lineages). HG1 itself defined by 92R7 consisted predominantly of R1b (actually P*).

Using the data from Table 1 suggests that the frequency of SRY2627 is highest in Basques, where it makes up 5/(19+5) ~ 21% of R1b. Its R1b frequency in northern Portuguese was 6/(6+203) ~2.9%. Similar values were obtained for Spanish samples. Based on very small numbers the Northern French R1b sample reached 2/(2+20) ~9%. The Bavarian R1b estimate was 2/(2+38) ~5%. Dutch and Belgian estimates were roughly half that figure. The only indication of it being present in Britain or Ireland came from Anglia where it had a frequency about 1%.

Based on STR haplotypes the Basques share many similarities with Irish, Cornish and Scottish R1b. It is commonly assumed that these Islands were re-inhabited after the LGM by R1b hunter/gatherers who moved into these regions from a refugia in Iberia as the ice receded. However, the high proportion of the SRY2627 mutation in Iberia, and its localization there, suggests it occurred after this dispersal, or that there were multiple isolated refugia in this region. The extent and distribution of SRY2627 based on the information presented above is uncertain for certain regions, especially France where it may be quite common. Its limited occurrence in Ireland and Britain, isolated to the south coast of Britain, may indicate introgression due to trading over the last several thousand years. However, more detailed sampling is required. Unfortunately this study did not do any associated STR genotyping.

The conservative conclusion, given the extremely limited sampling, is that the SRY2627 mutation occurred in R1b after the LGM and never made its way into Britain and Ireland in large numbers. It may provide a rare marker to distinguish between migration into Britain and Ireland after the LGM and subsequent predominantly R1b prehistoric “Celtic” invasions. If this is the case it suggests much less than 5% of the population was replaced in England by invading Celts. Typically Celts have been historically recorded as invading over a period ranging from 100-1000 BC. However, a much better sampling of France and Europe is required before definitive comments can be made on its value for this purpose.

Meyer et al. (2003) who typed bi-allelic markers produced the following results shown below in table 2 and figure 1.

The results identify that SRY2627 derived frequency is highest at around 11-14% in the North East corner of Spain and seems quite localized albeit only small numbers have been sampled so errors are large.

Garcia et al (2003) examined 178 controls and 208 patients in Oviedo Spain (Austurias region see figure 1) and found the results shown below in table 3. Genotype frequency of M167+ was 4-5%.

Table 3.

Association with STR haplotypes and estimates of age of the mutation

The first paper to report M167 mutation and STR haplotypes was Hurles et al (1999). The paper also detailed 7 marker STR haplotypes for the M167+ individuals and calculated the estimated age of the mutation. Frequencies are shown below in tabular and graphical format.

Table 4. Data from Hurles et al. 1999

Figure 2. Graphical presentation of the above distribution

Using a variety of methods Hurles et al (1999) estimated that the mutation occurred 1650-3450 yrs bp from the STR data. However, underpinning all these methods was the mutation rate and the estimate they used must have been rather high. The data has been reformatted and recalculated and the 36 M167+ 7 marker STR haplotypes submitted to Dean McGee’s calculator using an effective mutation rate of 0.0007/generation and a generation length of 28 years. The following results were obtained: the individual haplotypes are listed in table 5. Perhaps not surprisingly the modal value is the same as the modal value for R1b except for 389i & 389ii where possibly a different reporting convention has been used. There were 0-5 marker mismatches between individual haplotypes and the average TMRCA (50%) was 9874 yrs bp, markedly higher than that estimated by the authors.

Table 5. 7 STR marker haplotypes for M167+ individuals from Hurles et al (1999)

Ysearch Database Configuration - DNA Results Comparison

D
Y
S
3
9
3

D
Y
S
3
9
0

D
Y
S
1
9
/
3
9
4

D
Y
S
3
9
1

D
Y
S
3
8
5
a

D
Y
S
3
8
5
b

D
Y
S
4
2
6

D
Y
S
3
8
8

D
Y
S
4
3
9

D
Y
S
3
8
9
-
1

D
Y
S
3
9
2

D
Y
S
3
8
9
-
2

modal

Basque_m337

Basque_4301

Basque_46205

Basque_35v

Catalan_67c

Basque_m354

Basque_m362

Basque_m363

Madrid_ma19

British_m62

French_m147

Basque_m348

French_m95

Galician_ga29

Catalan_7c

Basque_m341

French_CEPH201

Bearnais_6201

Basque_8v

Basque_32v

Basque_98v

Basque_101v

Catalan_41c

Catalan_45c

Catalan_56c

Catalan_81c

Catalan_85c

Madrid_ma20

Spanish_sp21

Galician_ga22

Spanish_sp77

Spanish_sp79

Valencian_sp123

French_CEPH3501

German_ge3202

Andalucian_alm1

Distance from reference:

Zero

One

Two

Three+

Bosch et al (2001) used data from Underhill et al 2001 from Basques as well as other data collected for this study. No flow of M167+ individuals were detected in NW-Africa and its frequency was highest in Basque and Catalan populations. The STR genotypes are available, but were not extracted and summarized but a portion have been summarized in other studies.

Table 6. Note H103 =M167+

Brion et al (2004) examined 443 individuals in Northern Spain in 11 separate populations and observed frequencies ranging from 0 to 8%. The distribution is shown in the figure below.

Figure 3. Graphical distribution of M167+ (labeled R1b3f) figure from Brion et al 2004.

The estimates of frequency from this work are somewhat lower than previous studies, but there is a heavier sampling in the north-west part of Spain. Unfortunately, individual haplotypes were not reported but the more frequent ones were and are shown below in Table 5.

Table 7.

Pacheco et al (2005) found one M167+ individual in 178 samples in the Azores and found it had a STR haplotype of 13,17,24,10,13,13,11-14 at STR markers DYS389I,389II,390,391,392,393,385.

The final data set is Beleza et al (2005) and consists of a Portuguese sample of 663 individuals. R1b1c6 make up 13/355 R1b individuals or 3.7%. The 12 M167+ 15 marker STR haplotypes were submitted to Dean McGee’s calculator using an effective mutation rate of 0.0007/generation and a generation length of 28 years along with the calculated modals for the M167 and R1b modal. The following results were obtained.

Table 8. haplotypes

Ysearch Database Configuration - DNA Results Comparison

D
Y
S
3
9
3

D
Y
S
3
9
0

D
Y
S
1
9
/
3
9
4

D
Y
S
3
9
1

D
Y
S
4
3
9

D
Y
S
3
8
9
-
1

D
Y
S
3
9
2

D
Y
S
3
8
9
-
2

D
Y
S
4
3
7

D
Y
S
4
6
0

G
A
T
A
-
H
4

D
Y
S
4
3
8

D
Y
S
4
6
1

G
A
T
A
-
A
1
0

G
A
T
A
-
C
4

M167_modal

H538

H539

H540

H541

H542

H543

H544

H545

H546

H547

H548

H549

R1b_modal

Distance from reference:

Zero

One

Two

Three+

Table 9. Haplotype differences

Genetic Distance

M
1
6
7
_
m
o
d
a
l

H
5
3
8

H
5
3
9

H
5
4
0

H
5
4
1

H
5
4
2

H
5
4
3

H
5
4
4

H
5
4
5

H
5
4
6

H
5
4
7

H
5
4
8

H
5
4
9

R
1
b
_
m
o
d
a
l

M167_modal

H538

H539

H540

H541

H542

H543

H544

H545

H546

H547

H548

H549

R1b_modal

Related	Probably Related	Possibly Related
FTDNA's Interpreting Genetic Distance for 12 Markers
FTDNA's Interpreting Genetic Distance for 25 Markers
FTDNA's Interpreting Genetic Distance for 37 Markers

- Infinite allele mutation model is used
- Values on the diagonal indicate number of markers tested

The results identify several interesting points. Firstly, the M167+ modal is identical to the R1b modal, secondly, there is considerable diversity within the subclade with up to 9 mismatches out of 15 markers. The average TMRCA estimate was 8198 yrs bp using the method and assumptions described.

Summary

The interpretation of these combined results given the scarcity of the data is rather fraught. The first conclusion is that the M167+ mutation was soon after the formation of the R1b1c clade. The evidence for this is the lack of any modal differences in the two studies with R1b for the subclade, and the updated TMRCA estimates from Hurles et al 1999 and Beleza et al 2005 data both suggest an ancient origin. It should be noted that it would require an appreciable population size over an extended period to generate the diversity observed. The chance of extinction of a rare variant is very high over the estimated ~300 generations since its formation. The most probable explanation is that it is much more common than estimated in these studies, but with the exception of the Basques the regions of higher frequency have not been sampled. Specifically, it is suggested that this variant may be present in appreciable amount in South Western France. An alternative explanation is it was much more common and has subsequently declined in frequency.

References that have used M167 with summary comments

Abe-Sandes K, Silva WA Jr, Zago MA. Heterogeneity of the Y chromosome in Afro-Brazilian populations. Hum Biol. 2004 Feb;76(1):77-86. Review.

(Not available)

Bender K, Stradmann-Bellinghausen B, Rittner C, Schneider PM. Comparative analysis of short tandem repeats and single nucleotide polymorphisms on the Y-chromosome in Germans, Chinese and Thais. Leg Med (Tokyo). 2003 Mar;5 Suppl 1:S164-8.

(no M167 haplotypes reported in 95 Germans and none in Thai and Chinese as expected)

Beleza et al., Annals of Human Genetics (2005). Micro-Phylogeographic and Demographic History of Portuguese Male Lineages

(13/663 Portuguese individuals or 2% M167+)

Bosch E, Calafell F, Comas D, Oefner PJ, Underhill PA, Bertranpetit J.

High-Resolution Analysis of Human Y-Chromosome Variation Shows a Sharp Discontinuity and Limited Gene Flow between Northwestern Africa and the

Iberian Peninsula. Am. J. Hum. Genet., 2001, 68:1019-1029.

(reported 11% M167+ in northern Spain)

Brion M, Dupuy BM, Heinrich M, Hohoff C, Hoste B, Ludes B, Mevag B, Morling N, Niederstatter H, Parson W, Sanchez J, Bender K, Siebert N, Thacker C, Vide C, Carracedo A. A collaborative study of the EDNAP group regarding Y-chromosome binary polymorphism analysis. Forensic Sci Int. 2005 Oct 29;153(2-3):103-8.

(443 individuals in 11 separate populations in northern Spain frequency ranged from 0-8%)

Garcia EC, Gonzalez P, Castro MG, Alvarez R, Reguero JR, Batalla A, Cortina A, Alvarez V. Association between genetic variation in the Y chromosome and hypertension in myocardial infarction patients. Am J Med Genet A. 2003 Oct 15;122(3):234-7.

(4-5% M167+ Austurias region, Spain)

Khodjet el Khil H, Marrakchi RT, Loueslati BY, Langaney A, Fellous M, BenAmmar Elgaaied A. Distribution of Y chromosome lineages in Jerba island population.Forensic Sci Int. 2005 Mar 10;148(2-3):211-8.

(No M167 haplotypes reported in 135 samples)

Hurles ME, Veitia R, Arroyo E, Armenteros M, Bertranpetit J, Perez-Lezaun A, Bosch E, Shlumukova M, Cambon-Thomsen A, McElreavey K, Lopez De Munain A, Rohl A, Wilson IJ, Singh L, Pandya A, Santos FR, Tyler-Smith C, Jobling MA. Recent male-mediated gene flow over a linguistic barrier in Iberia, suggested by analysis of a Y-chromosomal DNA polymorphism. Am J Hum Genet. 1999 Nov;65(5):1437-48

(0-12% M167+, primarily located in the Iberian peninsula)

Maca-Meyer N, Sanchez-Velasco P, Flores C, Larruga JM, Gonzalez AM, Oterino A, Leyva-Cobian F. Y chromosome and mitochondrial DNA characterization of Pasiegos, a human isolate from Cantabria (Spain). Ann Hum Genet. 2003 Jul;67(Pt 4):329-39.

(1-14% M167+ in northern Spain depending on region)

Pacheco, PR, Branco CC, Cabral R, Costa, S, Araujo AL, Peixoto, BR, Mendonca, P, Mota-Vieira, L. 2004 The Y-chromosomal Heritage of the Azores Islands population Annals of Human Genetics (2005) 69,145-156

(1/172 or 0.6% were M167+ in the Azores which are primarily Portuguese descendants)

Rosser ZH, Zerjal T, Hurles ME, Adojaan M, Alavantic D, Amorim A, Amos W, Armenteros M, Arroyo E, Barbujani G, Beckman G, Beckman L, Bertranpetit J, Bosch E, Bradley DG, Brede G, Cooper G, Corte-Real HB, de Knijff P, Decorte R, Dubrova YE, Evgrafov O, Gilissen A, Glisic S, Golge M, Hill EW, Jeziorowska A, Kalaydjieva L, Kayser M, Kivisild T, Kravchenko SA, Krumina A, Kucinskas V, Lavinha J, Livshits LA, Malaspina P, Maria S, McElreavey K, Meitinger TA, Mikelsaar AV, Mitchell RJ, Nafa K, Nicholson J, Norby S, Pandya A, Parik J, Patsalis PC, Pereira L, Peterlin B, Pielberg G, Prata MJ, Previdere C, Roewer L, Rootsi S, Rubinsztein DC, Saillard J, Santos FR, Stefanescu G, Sykes BC, Tolun A, Villems R, Tyler-Smith C, Jobling MA. Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.

Am J Hum Genet. 2000 Dec;67(6):1526-43.

(0-19% of sample M167+ depending on location, mainly in Northern Spain)

Underhill PA, Shen P, Lin AA, Jin L, Passarino G, Yang WH, Kauffman E, Bonne-Tamir B, Bertranpetit J, Francalacci P, Ibrahim M, Jenkins T, Kidd JR, Mehdi SQ, Seielstad MT, Wells RS, Piazza A, Davis RW, Feldman MW, Cavalli-Sforza LL, Oefner PJ. Y chromosome sequence variation and the history of human populations. Nat Genet. 2000 Nov;26(3):358-61

(only present in 5/45 Basques [11%] from 1062 individuals surveyed worldwide)

Underhill PA, Passarino G, Lin AA, Shen P, Mirazon Lahr M, Foley RA, Oefner PJ, Cavalli-Sforza LL. The phylogeography of Y chromosome binary haplotypes and the origins of modern human populations. Ann Hum Genet. 2001 Jan;65(Pt 1):43-62.

(Not available)