Review of genetic diversity in Bactrian camel (Camelus bactrianus)

Research on the origin and domestication of Bactrian camel is helpful to understand the process of animal evolution and plays an important role in protecting the genetic diversity of Bactrian camel populations. New advances in research of the origin and domestication of Bactrian camel have been acquired by the rapid development of next-generation sequencing technology, molecular genetics, and bioinformatics. An overview given about the distribution, breeds, evolutionary history, and domestication, as well as the genetic diversity based on mtDNA, nuclear, and whole-genome sequencing of Bactrian camel populations. Bactrian camels (Camelus bactrianus) adapt to the specific weather conditions of both desert and semi-desert regions and provide a wide range of useful products to Gobi Desert rural communities, including meat, milk, and wool. In animal taxonomy, the Bactrian camel belongs to Animalia, Chordata, Mammalia, Placentalia, Artiodactyla, Tylopoda, and Camelidae. The family of Camelidae consists of the tribes Camelini (Old World camels) and Lamini (New World camels). The Camelini includes the Camelus genus, and the Lamini is divided into two genera, Lama and Vicugna. The genus Camelus includes three species, domesticated single-humped camel (dromedary, Camelus dromedarius), distributed in the arid deserts of North Africa, East Africa, and the Arabian Peninsula; domesticated two-humped camel (Bactrian camel, Camelus bactrianus), found in cooler areas of Asia (Faye and Konuspayeva, 2012), and the wild two-humped camel (Camelus ferus), considered critically endangered by the International Union for Conservation of Nature (Hare, 2008). The tribe Lamini comprises two domestic species of llama (Lama glama) and alpaca (Vicugna pacos) and two wild species of Guanaco (Lama guanicoe) and vicuña (Vicugna vicugna) (Saipolda, 2005; Wu et al., 2014). The classification of the family Camelidae is given in Figure 1. Taxonomy of the family Camelidae. To survive and live in harsh conditions, camels developed many special abilities and attributes. They can adapt to desert and semi-desert conditions—cold, hot, arid, poor grazing, and even food shortages, and can withstand extreme thirst and hunger for a long time due to sufficient energy in their humps and abdomen (Emmanuel and Nahapetian, 1980). The body temperature of the camel may vary from 34°C to 41°C throughout the day (Bouâouda et al., 2014). Different from other mammals, camels’ red blood cells are oval, which is conducive to water storage (Warda et al., 2014). They can consume diets toxic to other mammals due to their special metabolic pathways and unique detoxification capabilities (Hasi et al., 2018). Due to the extreme living environment in desert areas, they feed on Asteraceae and Chenopodiaceae, which have a high salt content, and herbaceous plants, bush, and cacti, which are rich in fiber but contain very little protein. Blood glucose levels in camels are twice those of other ruminants (Al-Ali et al., 1988). In addition, camelids are the only mammals that can produce heavy-chain antibodies (HCAbs), which lack the light chain, in contrast to conventional antibodies (Hamers-Casterman et al., 1993). In this review, we aim to provide a comprehensive summary of the distribution, breeds, evolutionary history, and domestication, as well as the genetic diversity based on mitochondrial DNA (mtDNA), nuclear, and whole-genome sequencing of Bactrian camel populations. Bactrian camel numbers and distribution vary from region to region. The ecological geographical distribution is in the transition from grasslands to desert areas; the higher the degree of desertification, the more Bactrian camels there are. Although the service value of Bactrian camels has substantially decreased, the trend of nurturing camels in the desert is increasing at the global level. Of the entire Bactrian camel population, more than 90% are found in China, Mongolia, and Kazakhstan. The Bactrian camel population was estimated to be 381,000 in China, 401,000 in Mongolia, and 170,000 in Kazakhstan in 2016 according to the Food and Agriculture Organization (FAO) statistics. The growth trend of Bactrian camels in China, Mongolia, and Kazakhstan from 2006 to 2016 is shown in Figure 2 (Jirimutu et al., 2022). The growth trend of Bactrian camels in China, Mongolia, and Kazakhstan from 2006 to 2016. Reprinted from the Material of Jirimutu et al. (2022). Based on distribution areas and phenotypic characteristics, several different breeds of Bactrian camel exist. In China, Bactrian camels are mainly distributed across Inner Mongolia, Xinjiang, Qinghai, and Gansu and are classified into five breeds: Alxa, Sonid, Qinghai, Tarim, and Junggar Bactrian camel (Jirimutu et al., 2009). Mongolian domestic Bactrian camels are mainly distributed in Umnegobi, Dornogobi, Dundgobi, Bayankhongor, and Gobi-Altai, and three breeds are recognized: Galbiin Gobiin Ulaan (GGU), Haniin Hetsiin Huren (HHH), and Tokhom-tungalag or Hos Zogdort (HZ) (Chuluunbat et al., 2014). In terms of camel breeding in Kazakhstan, camel breeds, such as Kazakh, Mongolian, and Kalmyk Bactrian camels are mainly bred and found in Almaty, Batysdykazakstan, Ongtustikkazakstan, and Aktube (Elmira et al., 2020). The most common locations and characteristics of Bactrian camel breeds are listed in Figure 3 and Table 1. Bactrian camel breeds in China, Mongolia, and Kazakhstan Bactrian camel breeds in China, Mongolia, and Kazakhstan Geographic locations of Bactrian camel breeds from China, Mongolia, and Kazakhstan. In addition, wild two-humped camels were discovered by Nikolaj Przewalski in 1878 (Peters and Driesch, 1997). As early as the 18th century, wild two-humped camels were widely distributed in many areas, such as Central Asia, reaching the Yellow River Bay in the East, the Qinghai Tibet Plateau in the south, the Caspian Sea in the West, and Baikal Lake in the north. The distribution area was continuous, and the total population was more than 10,000. In the early 1980s, investigations and estimations determined that there were 2,500 to 3,000 wild two-humped camels (Tulgat and Schaller, 1992). However, due to the impact of human activities and the deteriorating ecological environment, the distribution area of wild two-humped camels reduced, and the population declined. Nowadays, their range is limited to only four locations worldwide: three areas in China (Taklamakan Desert, Gashun Gobi Desert, and Arjin Mountains in the Lop Nur Lake region) and one in Mongolia (Great Gobi Strictly Protected Area “A”). At present, their total population was only 900 to 1,600, less than that of the giant panda (Yadamsuren et al., 2019). Although Bactrian camels are mainly distributed in Asia, their ancestors can be traced back to the Protylopus in the North American savannah during the Eocene period (~45 million years ago), measuring about 80 cm long and weighing 2.6 kg, with no hump, resembling the current hare (Rybczynski, 2013). In the Oligocene period (33.9 to 23 million years ago), camelids evolved rapidly. Named Poebrotherium, they lost two side toes, resembling the two-toed structure of modern camels. They still had no hump and stood about three feet tall, about the size of today’s deer. After the Oligocene period, the two-toed Protylopus gradually evolved into several genera of camelids, one of which evolved into the Procamelus during the Oligocene to Miocene period (20 to 5 million years ago). During this period, the Earth environment began to become dry and cold, and grasslands were replaced by sand. With the change in the environment, the Procamelus evolved a unique tooth and jaw structure similar to modern camels and had a similar pace as modern camels. During the Pliocene period (2.5 million years ago), North America and South America were connected, which brought opportunities for the migration of the Paracamelus, and the progenitors of Lamini entered South America around 3 million years ago (Rybczynski, 2013; Monchot, 2015). The others crossed the Bering Isthmus to Asia and evolved into dromedaries and Bactrian camels during the Late Miocene period (7.24 to 4.9 million years ago) (Honey et al., 2005). The divergence time between the Bactrian camel and dromedary was ~4.4 million years ago (1.9 to 7.2 million years ago) (Wu et al., 2014), and genetic studies confirmed (Ji et al., 2009; Silbermayr et al., 2010; Jirimutu et al., 2012; Mohandesan et al., 2017) that the wild two-humped camel was different from the domesticated camel, and the divergent time was estimated as 0.43 million years ago (95% confidence interval: 0.13 to 0.73 million years ago) by whole-genome sequencing (Ming et al., 2020a), which was slightly later than that based on mtDNAs (0.7 or 1.1 million years ago) (Ji et al., 2009; Mohandesan et al., 2017). Based on the geological fossil data found by paleontologists (Reitz and Wing, 2008), the period of Bactrian camel domestication was estimated as 4,500 years ago, and the evidence related to domestication regions was mainly concentrated in Northern Iran and Southern Turkmenistan (Bulliet, 1975). However, some scholars believed that in addition to Iran and Turkmenistan, the domestication areas of Bactrian camels also included southern Kazakhstan, Western Mongolia, and Northern China, mainly based on the existence of wild two-humped camels in these areas (Peters and Driesch, 1997). For a long time, according to the individual morphological and anatomical characteristics of domestic Bactrian camel and the extant wild two-humped camel, it was speculated that the domestic Bactrian camel was domesticated from the extant wild two-humped camel. Nevertheless, molecular genetics research based on mtDNAs (Ji et al., 2009; Mohandesan et al., 2017) and Y chromosomes (Felkel et al., 2019) discovered dramatic sequence variations between domestic and the wild two-humped camel, suggesting that they were not the same subspecies, at least in their maternal origins. Furthermore, the haplotypes of skeletal mitochondrial partial sequences of 12 Bactrian camel bones from Late Bronze and Early Iron Age sites found in Uzbekistan and Syria were shared with modern domestic Bactrian camels (Trinks et al., 2012) but different from those of extant wild two-humped camels, suggesting only one domestication event; that is, the wild two-humped camel was a separate lineage. Another possible place of origin was Iran, where early skeletal remains of domestic Bactrian camels (around 2500 to 3000 BC) were discovered (Yam and Khomeiri, 2015). However, incomplete archaeological findings provided little conclusive information about the actual domestication history of Bactrian camels. Recently, the whole-genome sequencing including domestic and the wild two-humped camels were used to reveal the origin, migration, and domestication of Bactrian camel (Ming et al., 2020a). A significantly higher genetic diversity and divergence were displayed in the Iranian camels, and the earliest branching among the domestic Bactrian camels occurred between Iran and all the other Bactrian camel populations. Although evident introgression of dromedaries was observed in Central Asia (11,711 non-overlapping 100 kb segments, Z-score >2) by using the “BABA/ABBA,” the study demonstrated that it will not influence the results by removing the introgressed genomic segments (Ming et al., 2020a). Therefore, it is valid to assume that Bactrian camels were first domesticated in Central Asia less than 4.45 thousand years ago, and then migrated back to East Asia around 2.40 thousand years ago (Figure 4). A proposed migration route of Bactrian camels. Reprinted from the Supplementary Material of Ming et al. (2020a). While the Bactrian camel made a great contribution to transportation on the Silk Road and could be portrayed as a bridge between Eastern and Western cultures, little is known about the camel genome. The first draft of the Bactrian camel genome was completed in 2012 (Jirimutu et al., 2012). The estimated size of the Bactrian camel genome was 2.38 Gb, close to the camel genome size (2.02 to 2.40 Gb) calculated based on haploid DNA contents (C values). They predicted 20,821 protein-coding genes, averaging eight exons and a 1322-bp coding region per gene. Based on phylogenetic analysis, the authors also revealed that the camel shared a common ancestor with even-toed ungulates around 55 to 60 million years ago. Rapidly evolving genes were significantly enriched in metabolic pathways, perhaps helping Bactrian camels optimize their energy storage and production in the desert. The olfactory receptors were enriched in lower heterozygosity genomic regions in the domestic camel. After annotation, the results also suggested that the specific cytochrome P450 families and unusual immune system were useful for survival in the desert (Jirimutu et al., 2012). Subsequently, a male Bactrian camel’s genome was de novo assembled (Burger and Palmieri, 2014), and the genome size reached 1.6 Gb. More than 116,000 heterozygous SNPs were detected, and the genome-wide nucleotide diversity was similar to that of other domesticated ungulates (cattle and pig) based on average 6.6-fold coverage (Burger and Palmieri, 2014). A similar report related to sequencing the genome of Bactrian camel, dromedary, and alpaca was published in 2014 (Wu et al., 2014). The estimation of the Bactrian camel genome size reached 2.45 Gb, predicting the presence of 20,251 genes, similar to the earlier report (Jirimutu et al., 2012). Evolutionary analysis found that the Bactrian camel and the dromedary had higher non-synonymous/synonymous (Ka/Ks) substitution ratios (ω-values), which raised the possibility of Bactrian camels adapting to the harsh desert environment. Comparative genomics analyses also revealed complex features related to desert adaptations, including fat and salt metabolism, stress responses to arid and hot environments, and intense ultraviolet radiation. Transcriptomic analysis of Bactrian camels further showed unique osmoregulation, osmoprotection, and compensatory mechanisms for water reservation underpinned by high blood glucose levels (Wu et al., 2014). A perfect assembly report, related to high-coverage long-read sequencing and chromatin interaction mapping of wild two-humped camel genome, was completed in 2020 (Ming et al., 2020b). This analysis assembled the most contiguous Bactrian camel genome to date, and exhibited remarkable improvement over existing short-read assemblies of the same species. The contig N50 reached 5.37 Mb and the scaffold N50 was 76.03 Mb. The authors also illustrated that immunoglobulin and T-cell receptor gene loci could be uniquely localized to specific chromosomes, and the classical major histocompatibility complex region was resolved into a single contig without any gaps. Genomic comparison of Bactrian camels from different research was shown in Table 2. Genomic comparison of Bactrian camels from different research aSee Jirimutu et al. Wu et al. and Ming et al. Genomic comparison of Bactrian camels from different research aSee Jirimutu et al. Wu et al. and Ming et al. The mitochondrial genome has the characteristics of maternal a high evolution and no and has been used as a genetic of genetic diversity in The first molecular evolutionary analysis of the family Camelidae by the mitochondrial cytochrome gene et al., revealed that the divergence time of and New World tribes was with the fossil This the for to the evolution of Camelidae. et al. the mitochondrial genome of wild two-humped and domestic Bactrian camels by which showed that there were in at three between In addition, high of mitochondrial sequence divergence between domestic Bactrian and wild two-humped camels had been revealed using the sequence of mitochondrial gene (Ji et al., 2009). using an mitochondrial the authors that there were eight haplotypes domestic camel haplotypes and two wild two-humped camel in wild and domestic Bactrian camels from Mongolia, China, and and found high sequence divergence between wild two-humped and domestic Bactrian camels et al., In different domestic breeds, the genetic diversity and population structure based on the different mitochondrial The genetic diversity and structure were based on the (Ming et al., 2017) and the gene (Ming et al., in domestic Bactrian from different including China, Mongolia, and and one wild two-humped camel from The domestic and wild two-humped camels had two and the wild two-humped camels displayed lower levels of nucleotide and The levels of nucleotide and diversity Mongolia were slightly higher than those of camels from China and there was no genetic divergence among different geographical which a gene due to the wide of domestic Bactrian camels (Ming et al., 2017). Subsequently, research based on the mitochondrial and genes also confirmed this et al., 2017). However, research by et al. showed that there at least two maternal of domestic Bactrian camels, and the divergence time of was estimated as thousand years ago (95% to thousand years ago), that several different evolutionary were into the domestic gene during the domestication Recently, a comprehensive study was completed to reveal genetic diversity by region sequences of from World camels (Ming et al., haplotypes were confirmed in Bactrian camels, including domestic and wild two-humped camels, haplotypes were in The wild two-humped camel showed the and nucleotide the dromedaries had the the phylogenetic among domestic Bactrian camel population haplotypes was shown that haplotypes of population from different regions Mongolia, Iran, and not according to their regions (Figure and there were several shared haplotypes and between can be predicted domestic Bactrian camels between different haplotypes specific to a region were also such as five haplotypes to only in Bactrian and only found in Iran Bactrian haplotypes and were only discovered in Bactrian camels, and there were 12 haplotypes were only found in Mongolian Bactrian camels (Ming et al., for domestic Bactrian camel population haplotypes from China, Mongolia, Iran, and Kazakhstan. The areas of the were to the of population from different such as China, Mongolia, Iran, and Kazakhstan, not according to their Reprinted from the Material of Ming et al. In Mongolian domestic breeds, traced possible and between the three breeds and the common Mongolian camel (Chuluunbat et al., 2014). The nucleotide and diversity were lower in than in and breeds, and some haplotypes were shared by in the three breeds and one The diversity was lower than that of Ming et study (Ming et al., 2017). A study on the genetic diversity of Bactrian camels from China and The population genetic diversity was on Bactrian and 5 wild two-humped camels from China and Mongolia using data from et al., 2008). The analysis of genetic and showed that there was no genetic in the domestic Bactrian camels between China and Mongolia, there was genetic between and wild two-humped camels et al., 2008). In addition, that there rich genetic diversity among five domestic Bactrian camel from China based on 2009). In to the genetic and possible at the molecular Bactrian camel camel and Mongolian camel from China and Mongolia were using the Bactrian camel had rich genetic and the genetic among the was with of the total genetic among the and the among the et al. the genetic diversity in Mongolian Bactrian camels using and found levels of genetic diversity in Mongolian similar to those for Bactrian camels. was between single breeds, for a from the Mongolian region (Chuluunbat et al., 2014). to domestication history, the Bactrian camel is one of the to have population genome and genetic diversity The domestic Bactrian camels were to as many major regions as including China, Mongolia, Kazakhstan, and Iran and to the dromedary from Iran (Ming et al., 2020a). The nucleotide diversity of dromedaries was significantly higher than that of Bactrian camels from all regions to among the Bactrian camels, the wild two-humped camels showed the with all the domestic with the nucleotide diversity based on mitochondrial (Ming et al., 2017). In addition, the domestic living in Central Asia showed higher diversity to than those living in East Asia to The was also confirmed by (Figure The nucleotide diversity and of the camel populations. Reprinted from the Material of Ming et al. (2020a). 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