DOI: 10.13102/sociobiology.v65i3.2876Sociobiology 65(3): 482-490 (September, 2018) 

Open access journal: http://periodicos.uefs.br/ojs/index.php/sociobiology
ISSN: 0361-6525

Genetic Variation in Iranian Honey bees, Apis mellifera meda Skorikow, 1829, (Hymenoptera: 
Apidae) Inferred from PCR-RFLP Analysis of two mtDNA Gene Segments (COI and 16S rDNA)

Introduction

Intraspecific taxonomy of the honey bee Apis mellifera 
L. has been based mainly on morphology. At present, 29 
subspecies of A. mellifera are recognized on the basis of 
morphometric characters (Ruttner, 1988, 1992; Sheppard et 
al., 1997; Sheppard & Meixner, 2003; Arias & Sheppard, 
2005; Meixner et al., 2011 Rahimi et al., 2017). The western 
honey bee originated in Asia and entered Africa and Europe 
in three distinct evoluationary branches: branch (A), which 
included the subspecies from Africa (A. m. lamarckii, A. m. 

Abstract
In this study, the genetic structure of Iranian honey bee (Apis mellifera meda) populations, 
mainly obtained from all of regions, were investigated at two different mitochondrial 
regions. A total of 300 worker bees were collected from 20 different populations in 
20 different locations. Portions of the mitochondrial 16S ribosomal RNA (16S rDNA) 
and cytochrome C oxidase I (COI) genes were amplified by PCR and then subjected 
to RFLP pattern analysis using 8 restriction enzymes. Nucleotide polymorphisms were 
revealed using restriction enzyme Sau3A I, Ssp I and Taq I in COI and Bsp143I, Ssp I 
and Dra I in the 16S rDNA gene segment. In this study, 3 novel composite genotypes 
(haplotypes) were found in Iranian honey bee populations. The average haplotype 
diversity (h) within populations was 0.0405. Heterozygosity values, Shannon index and 
the number of alleles of Iranian honey bee populations were low that could be caused 
by low definite geographic structure of Iranian honey bee populations. Genetic distance 
(D) values were found to be low (0.0–0.0011) within Iranian honey bee populations. 
Cluster analysis based on UPGMA method revealed that all populations and samples 
groups be in one cluster. Also, the phylogenetic tree based on Neighbor-joining method 
divided 29 subspecies of honey bee to 5 distinct clusters. The Iranian subspecies honey 
bee composed of a shared clade with subspecies of Eastern Mediterranean, Near East 
and Eastern parts of Middle East (O branch). This result is very useful for the control of 
conservation of local honey bees, as the movement of colonies across the border line of 
these neighboring countries, may affect the genetic structure of honey bee populations.

Sociobiology
An international journal on social insects

A Rahimi1,2, A Mirmoayedi1, D Kahrizi3, L Zarei3, S Jamali1

Article History

Edited by
Marco Costa, UESC, Brazil
Received                  04 February 2018
Initial acceptance   03 June 2018
Final acceptance    05 September 2018
Publication date     02 October 2018

Keywords 
Apis mellifera; Genetic structure, mtDNA, 
Iran. 

Corresponding author
Ataollah Rahimi
Department of Plant Protection
Faculty of Agriculture, Campus of 
Agriculture and Natural Resources
Razi University, Kermanshah, Iran.
E-Mail: Rahimi.ata.1@gmail.com

yemenitica, A. m. scutellata, A. m. litorea, A. m. adansonii, 
A. m. capensis), branch (M) which included the subspecies 
of North African and West European (A. m. mellifera, A. m. 
iberica, A. m. intermissa and branch (C) which included the 
subspecies from Eastern Europe, Northern Mediterranean and 
Middle East. Afterwards, subspecies in branch C were divided 
into two groups, branch C included A. m. carnica, A. m. 
ligustica, A. m. macedonica, A. m. cecropia and A. m. sicula, 
branch O included the Near and Middle Eastern subspecies (A. 
m. caucasica, A. m. armeniaca, A. m. meda, A. m. anatoliaca, 
A. m. syriaca, A. m.cypria, A. m. adami) (Ruttner, 1988). The 

1- Department of Plant Protection, Faculty of Agriculture, Campus of Agriculture and Natural Resources, Razi University, Kermanshah, Iran
2- Department of Animal Science, College of Agriculture - Kifri, Garmian University, Kalar, As Sulaymaniyah, KRG of Iraq
3- Department of Plant Breeding and Biotechnology, Faculty of Agriculture, Campus of Agriculture and Natural Resources, Razi University, 
Kermanshah, Iran

RESEARCH ARTICLE - BEES



Sociobiology 65(3): 482-490 (September, 2018) 483

phylogenetic relationships based on molecular data (Cornuet 
& Garnery, 1991; Garnery et al., 1992; Arias & Sheppard, 
1996) agree in general with those obtained with confirmed 
using mitochondrial and microsatellite variability (Franck et 
al., 2000; Palmer et al., 2000; Kandemir et al., 2006; Rahimi, 
2014a,b). Southwest Asia included Iran is a region of high 
morphological diversification and evolution for honey bees. 
One clearly distinct race has been evolved in this region, 
which include a diversity of habitats. Honey bee race in this 
region include the subspecies A. m. meda (Ruttner, 1988). 
Honey bee subspecies from Iran was studied extensively using 
morphometric and izoenzymic analysis (Moradi & Kandemir, 
2004; Rahimi & Asadi, 2010; Rahimi & Mirmoaydi, 2013; 
Rahimi et al., 2014a,b; Rahimi et al., 2015a; Rahimi et al., 
2017); molecular markers, mitochondrial DNA (mtDNA) 
analysis (Rahimi et al., 2014a,b; Rahimi et al., 2015b; Rahimi 
et al., 2016); microsatellite and RAPD analysis (Royan et al., 
2007; Kamrani et al., 2012; Rahimi et al., 2014a,b). More 
recently, genetic systems such as allozymes (Nunamaker & 
Wilson, 1982; Badino et al., 1988), nuclear DNA (Hall, 1990; 
Tarès et al., 1993), mitochondrial DNA (mtDNA) (Moritz et 
al., 1986; Smith et al., 1989, 1991; Hunt & Page, 1992; Garnery 
et al., 1993; Oldroyd et al., 1995; Arias and Sheppard, 1996; 
Pedersen, 1996; De la Rùa et al., 2000) and microsatellites 
(Estoup et al., 1993; Garnery et al., 1998) have been used to 
study honey bee diversification. Such analysis of population 

genetic differentiation at the molecular level contributes to 
better understanding of honey bee population structure by 
allowing the comparison of morphological, behavioural, 
geographical and molecular variation. The mtDNA is a 
favourite tool in systematic and population biology. It is 
generally maternally inherited without recombination. Only 
maternal inheritance of mtDNA has been demonstrated for 
honey bees (Smith, 1991; Meusel & Moritz, 1993; Arias & 
Sheppard, 1996; Francisco et al., 2001; Pinto et al., 2003). 

Iran is a vast country comprising a land area about 
1648195 km2. From the geographical point of view, Iran has a 
very diverse climatic condition with diverse patterns of plant 
communities forming four climatic zones simultaneously; 
therefore it has a high potential for beekeeping and honey 
production. Therefore, genetic structure maintenance and 
preservation of Iranian honey bees is the first step to explore 
of this potential. The main aim of the present research was to 
determine the level of genetic differentiation among Iranian 
honey bee populations as discriminated using PCR-RFLP 
pattern analysis of the COI and 16S rDNA gene regions of 
mtDNA, and also the results of this study were compared 
with the results of other earlier mitochondrial studies of 
honey bees, such comparison thereby allowing much more 
complete estimation of the genetic structure of Iranian honey 
bee populations than until now previously possible using 
morphometrics alone.

Fig 1. Geographical locations of the 20 sampled honey bee populations in Iran. N is the number of 
sampled bees per population.



A Rahimi, A Mirmoayedi, D Kahrizi, L Zarei, S Jamali – Genetic variation in Iranian honey bee484

Materials and Methods

Sampling 

A total of 300 young adult worker bees from 150 
Apis mellifera meda colonies were sampled in 100 different 
localities from 20 Iranian provinces during June to October 
2014 (Fig 1, Table 1). Samples were taken from honey bee 
colonies in most active apiaries from five cities in each 
province, one apiary in each city and one to three hive per 
apiary. Young adult worker bees directly were collected from 
the broad areas on the combs. The samples were immediately 
killed by immersion in absolute ethanol and kept at –20 ºC 
until DNA extraction. 

Molecular analysis
DNA extraction

Total genomic DNA was extracted from the head and 
thorax sections of each honey bee worker, using the salting 
out method described by Aljianabi and Martinez, (1997) with 
slight modifications and then stored at −20 ºC.

RFLP Analysis

The mtDNA variation was analyzed by RFLP’s, performed 
on PCR amplified products. Mitochondrial regions were amplified 
according to Bouga et al. (2005). Two sets of primers were used 

for amplifying 16S rDNA and COI gene regions. These were 5’- 
CAACATCGAGGTCGCAAACATC-3’ and 5’-GTACCTTTT 
GTATCAGGGTTGA-3’ for 16S rDNA and 5’-GATTA  
CTTCCTCCCTCATTA-3’ and 5’-AATCTGGATAGTCTG 
AATAA-3’for COI segment. PCR was run in a total volume 
25 µl of the following reaction mixture: 2.5 µl of 10 X reaction 
buffer with KCl as provided by the manufacturer (Fermentas 
Life Sciences, Vilnius, Lithuania), 1 mM MgCl2, 0.5 mM of 
dNTP mix, 1 µM of each primer, 2 U of Taq polymerase and 
20 ng of total purified honey bee DNA. For each primer pair, 
the following reaction profile was used: initial denaturation 
94 °C for 4 min, 35 cycles of 94 °C for 1 min, annealing at 55 
°C for 1 min, and extension at 72 °C for 2 min, followed by a 
final extension step at 72 °C for 10 min.

The amplified products obtained were next electro-
phoresed on 1% agarose gel to verify the size of the fragment. 
Amplified mtDNA regions from one individual of each bee were 
digested with 8 restriction enzymes to check for the presence 
of recognition sites. The informative restriction enzymes were 
then analyzed using one individual from each colony. The 
informative restriction enzymes used for the 16S rDNA gene 
fragment were: Sau3A I, Ssp I, Dra I, and EcoR I, and for the 
COI gene fragment Sau3A I, Ssp I, Taq I and NcoI.

The digested fragments were separated electrophore-
tically on 2% or 3% agarose gels in 1× TBE buffer, stained with 

Table 1. Sampling localities, geographical positions and the number of honey bees used for PCR-RFLP analysis in Iranian honey bee.

Province/ 
locations

Abbreviation of the 
province/ locations

The number 
of apiary

The number 
of  colonies

The number 
of  bees

Geographical position
Latitude Longitude altitude

Kermanshah KER 5 7 14 34° 29′ 15.62 N 047° 05′ 57.65 E 1664
Hamadan HAM 5 8 16 34° 43′ 24.64 N 048° 31′ 01.27 E 2464
Ilam ILA 5 5 10 33° 34′ 31.97 N 046° 27′ 26.44 E 1548
Lorestan LOR 5 6 12 33° 32′ 01.81 N 048° 14′ 12.03 E 1802
Esfahan ESF 5 10 20 32° 36′ 56.09 N 051° 34′ 04.20 E 1618
Chaharmahal 
and Bakhtiari

CHA 5 7 14 32° 28′ 19.40 N 050° 06′ 30.53 E 2582

Fars FAR 5 10 20 28° 59′ 19.33 N 053° 39′ 56.47 E 1563
Sistan and 
Baluchestan

SIS 5 5 10 29° 30′ 53.89 N 060° 50′ 17.17 E 1407

Kerman KRM 5 6 12 29° 18′ 19.25 N 057° 08′ 29.72 E 2838
Kurdistan KUR 5 7 14 34° 42′ 48.06 N 046° 51′ 34.16 E 1775
West Azerbaijan WEA 5 10 20 37° 34′ 04.14 N 044° 44′ 17.19 E 2138
East Azerbaijan EAA 5 10 20 38° 06′ 13.12 N 046° 11′ 10.99 E 1345
Ardabil ARD 5 9 18 38° 13′ 58.28 N 048° 10′ 05.22 E 1455
Zanjan ZAN 5 6 12 36° 42′ 37.00 N 048° 22′ 25.99 E 1546
Tehran TEH 5 6 12 35° 43′ 44.11 N 052° 07′ 00.70 E 2233
Razavi Khorasan REK 5 7 14 36° 25′ 56.06 N 059° 31′ 26.22 E 922
North Khorasan NOK 5 6 12 37° 29′ 16.88 N 057° 09′ 56.89 E 1454
Golestan GOL 5 5 10 36° 50′ 47.46 N 054° 40′ 12.88 E 181
Mazandaran MAZ 5 10 20 36° 25′ 22.19 N 052° 14′ 39.71 E 135
Gilan GIL 5 10 20 36° 50′ 23.28 N 049° 25′ 57.83 E 329
Total 150 300



Sociobiology 65(3): 482-490 (September, 2018) 485

ethidium bromide, visualized under UV light and photographed 
using a Vilber Lourmat gel imaging system. The sizes of DNA 
fragments were compared to the PCR marker (Promega G316A, 
Promega Corp.) run on the same gel and were calculated using 
DNA frag 3.03 (Nash, 1991) program.

Data analysis

Composite genotypes for each individual were then 
defined from all the restriction patterns of the two mtDNA 
segments. The restriction fragment data were converted to 
restriction data (gain or loss of restriction site). The POPGENE 
software version 1.31 was used for estimating population 
genetic structure. The genetic distance from restriction site 
data (Nei & Tajima, 1981; Nei & Miller, 1990) was estimated 
using the REAP computer package (McElroy et al., 1991). 
Phylogenetic tree was constructed by the Neighbor-joining 
method, based on results of genetic distance from restriction 
site data, using the PAST package version 2.02. Results from 
analogous study on honey bees from different areas for other 
subspecies of honey bee were included in the above mentioned 
statistical process.

Results

The sizes of the PCR-amplified mtDNA regions for 
all populations studied were found to average 964 bp for 
16S rDNA and 1028 bp for COI mtDNA gene regions. Eight 
restriction enzymes were found to have at least one restriction 
site in the amplified 16S rDNA and COI regions, respectively. 
Observed fragment patterns generated by each restriction 
enzyme for the two mtDNA regions are summarized in Table 
2. Sau3A I, Ssp I and Taq I restrictions in COI and Sau3A 
I, Ssp I and Dra I restriction in the 16S rDNA gene each 
generated two different restriction profiles in Iranian honey 
bee populations (Table 2). Diagnostic and novel patterns 
were revealed in the East Azerbaijan (EAA), West Azerbaijan 
(WEA) and Sistan and Baluchestan (SIS) populations after the 
digestion of 16S rDNA and COI segment with the restriction 
enzymes Bsp143I, Ssp I and Dra I and Sau3A I, Ssp I and Taq 
I, respectively (pattern type A).

The three different and novel haplotypes (composite 
genotypes) which were detected in the twenty populations 
studied and the haplotype frequencies and haplotype diversity 

values are presented in Table 3. The three novel haplotypes 
were found in East Azerbaijan (EAA), West Azerbaijan 
(WEA) and Sistan and Baluchestan (SIS) samples. The average 
haplotye diversity (h) within populations was 0.0405 (Table 3).

The number of alleles (Na) and the effective number 
of alleles (Ne), the observed and expected heterozygosities 
(Ho and He) and Shannon index (I) per COI and 16S rDNA 

COI 16S rDNA
Restriction enzyme Patterns observed (bp) Restriction enzyme Patterns observed (bp)

Sau3A I
A: 338, 315, 168, 75, 72, 60
B: 398, 315, 168, 75, 72

Sau3A I
A: 964
B: 545, 419

Ssp I
A: 520, 210, 170, 80, 48
B: 520, 258, 170, 80

Ssp I
A: 515, 335, 114
B: 630, 334

Taq I
A: 350, 262, 244, 172
B: 432, 352, 244

Dra I
A: 314, 212, 118, 115, 90, 70, 45
B: 359, 212, 118, 115, 90, 70 

NcoI 1028 EcoR I 494, 470

Table 2. Restriction fragment patterns generated from analysis of COI and 16S rDNA gene segments of Iranian honey bee.

Fig 2. Cluster analysis of 300 honey bee individuals from twenty 
provinces of Iran based on UPGMA method.



A Rahimi, A Mirmoayedi, D Kahrizi, L Zarei, S Jamali – Genetic variation in Iranian honey bee486

mtDNA gene and per restriction enzyme in Iranian honey bee 
populations are shown in Table 4.

The genetic distance (D) values were found to be low 
(0.0 – 0.0011) within Iranian honey bee populatioins (Table 5). 

Phylogenetic trees are generally plotted to find the 
genetic distances between the collected samples of honey bees. 
Cluster analysis based on UPGMA method between all samples 

Haplotype
Composite genotype

Haplotype 
diversity (h)

NCOI 16S rDNA
Sau3A I Ssp I Taq I NcoI Sau3A I Ssp I Dra I EcoR I

Kermanshah A A A A A A A A 0.00 14
Hamadan A A A A A A A A 0.00 16

Ilam A A A A A A A A 0.00 10
Lorestan A A A A A A A A 0.00 12
Esfahan A A A A A A A A 0.00 20

Chaharmahal and 
Bakhtiari

A A A A A A A A 0.00 14

Fars A A A A A A A A 0.00 20
Sistan and 

Baluchestan
B B B A B B B A 0.18 10

Kerman A A A A A A A A 0.00 12
Kurdistan A A A A A A A A 0.35 14

West Azerbaijan B B B A B B B A 0.28 20
East Azerbaijan B B B A B B B A 0.00 20

Ardabil A A A A A A A A 0.00 18
Zanjan A A A A A A A A 0.00 12
Tehran A A A A A A A A 0.00 12

Razavi Khorasan A A A A A A A A 0.00 14
North Khorasan A A A A A A A A 0.00 12

Golestan A A A A A A A A 0.00 10
Mazandaran A A A A A A A A 0.00 20

Gilan A A A A A A A A 0.00 20
Haplotype 

diversity (h)
0.0405

Table 3. Composite genotypes (haplotypes), haplotype diversity and sample size of all the populations studied.

mtDNA 
gene

Restriction 
enzymes

Na Ne HO He I

COI

NcoI 1 1 0.001 0.001 0.001

TaqI 3 1 0.001 0.001 0.001

SspI 5.1 1.001 0.002 0.002 0.0009

Sau3AI 6.1 1.002 0.004 0.004 0.0033

16S 
rDNA

EcoRI 2.2 1.003 0.006 0.006 0.0016

DraI 6.1 1.003 0.003 0.003 0.0033

PstI 2.1 1.003 0.005 0.005 0.0033

TaqI 2.1 1.003 0.005 0.005 0.0033

Table 4. Genetic parameters: the number of alleles (Na) and 
the effective number of alleles (Ne), the observed and expected 
heterozygosities (Ho and He) and Shannon index (I) per COI and 
16S rDNA mtDNA gene and per restriction enzymes in Iranian 
honey bee populations.

in this study shown in Fig 2. The results of this cluster showed 
that all populations and samples groups be in one cluster.

Phylogenetic tree based on RFLP analysis was drawn 
using Neighbor-joining method to compare phylogenetic 
relationships Iranian subspecies honey bee with other honey 
bee subspecies. Phylogenetic tree showed that 29 honey bee 
subspecies could be divided into 5 distinct groups (Fig 3).

Discussion

In a recent study of Iranian honey bee samples, we 
earlier showed that all honey bee samples then tested belonged 
to the East Mediterranean (C) lineage as found using several  
restriction enzymes and morphological characters 
(Rahimi, 2015b; Rahimi et al., 2017). In the present 
study, we have used different two mtDNA regions with 
different samples of the mitochondrial genome to verify 
the nature and distribution of genetic variation within and 
between Iranian honey bee populations. The results of Fig 
3 showed that Iranian honey bee belong to evolutionary 
lineages (C) and confirmed the results of previous studies.  
It is remarkable that several technical improvements introduced 
in beekeeping management may have interfered with the 
natural distribution of populations. The importation of foreign 



Sociobiology 65(3): 482-490 (September, 2018) 487

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. Fig 3. Phylogenetic tree between 29 honeybee subspecies based on 
Neighbor-joining method. 

queens and the practice of moving colonies several times per 
year are factors that can affect the genetic structure of a local 
honey bee population through genetic introgression (Garnery 
et al., 1998).

In comparison our results with Bouga et al. (2005), 
Kekeçoglu et al. (2009) and Ozdil et al. (2012), we find 
similar restriction profiles with generally small base 
differences in the fragments, except for Sau3A I, Ssp I and 
Taq I and Bsp143I, Ssp I and Dra I digestions in COI and 16S 
rDNA gene regions, respectively (Table 2). In these regions, 
different restriction profiles were detected in our samples 
or populations. Sau3A I, Ssp I and Taq I restriction in COI 
revealed six or five, five or four and four or three restriction 
sites in this study, respectively, whereas in others subspecies 
such as A. m. anatoliaca, A. m. caucasica and A. m. meda 
(in Turkey), restriction analysis were previously reported to 
have revealed four or six, three or two and two restriction 
sites for these enzymes, respectively (Bouga et al., 2005, 
Kekeçoglu et al., 2009, Ozdil et al., 2012). Correspondingly, 
the restriction of the 16S rDNA gene region with Sau3A I, 
Ssp I and Dra I revealed two or one, three or two and seven 
or six sites (Table 2), compared with the three or two, two and 
two or seven as reported in Turkish honey bees (Bouga et al., 



A Rahimi, A Mirmoayedi, D Kahrizi, L Zarei, S Jamali – Genetic variation in Iranian honey bee488

2005, Kekeçoglu et al., 2009, Ozdil et al., 2012). Comparing 
our findings with these of Ozdil et al. (2012), honey bees in 
Iran and Turkey (specially A. m. meda) were found to be well 
discriminated; it is noted that for the first time are reported 
diagnostic patterns that distinguish the honey bee populations 
of these neighboring countries. Honey bees from Iran are also 
discriminating from other subspecies of honey bees in Turkey, 
Iraq and Syria. 

This study indicated that Iranian honey bee populations 
were characterized by a low variability in the number of 
alleles (Na) and the effective number of alleles (Ne), the 
observed and expected heterozygosities (Ho and He) and 
Shannon index (I). According to results of cluster analysis 
(Fig 2), it should be concluded that the honey bees of these 
twenty populations have formed one population, and there is 
no special divisions among them. Also, the cluster analysis 
showed that honey bees from different cities and provinces 
are scattered across the branches of the phylogenetic tree and 
apparently belong to the same population. This information 
showed that genetic diversity between Iranian honey bee 
populations is low, so we need a comprehensive breeding 
program for breeding of Iranian honey bee. However, the 
above mentioned results are very useful for the conservation 
of Iranian honey bee, but further follow up studies are needed 
to characterize mitochondrial DNA variation in the honey 
bees of these regions along with morphometric analyses in 
order to accurately characterize the particular regional honey 
bee populations.

Acknowledgements

The authors appreciate the kindness of those beekeepers 
who allowed us to collect honey bee samples from their 
apiaries and equally thank the authorities of Plant Protection 
and Biotechnology departments of Razi university who let us 
a free access to laboratory facilities which led to fulfill of the 
present study. 

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