A Study of the Genetic Structure of Hybrid Camels in Kazakhstan.

Camel farming is gaining scientific interest due to its unique agricultural characteristics. Camels are versatile for milk and meat production, wool, racing, transport, and tourism. To use their full potential, it is essential to improve our understanding of the genetic structure of these animals. One-humped and two-humped camels have received detailed genetic descriptions, while there is no such information for their hybrids, which outperform their parent species in several agricultural characteristics. Thus, in this study, for the first time, the whole genome sequencing data (WGS) of five hybrid camels bred in the Almaty region of Kazakhstan are presented in comparison with the WGS data of one-humped, two-humped, and wild camels. A total of 43,552,164 single-nucleotide polymorphisms were found across the studied groups. Further comparison of these SNPs showed the following number of private SNPs among the populations: hybrid camels (3,271,083), wild camels (2,515,591), Bactrians (1,244,694), and dromedaries (531,224). The genetic structure of the studied animals was described, and a phylogenetic tree was built to assess their genetic distance. It was found that the studied hybrids are genetically closer to dromedaries since they were on the close branch of the phylogenetic tree.

Kazak mitochondrial genomes provide insights into the human population history of Central Eurasia.

As a historical nomadic group in Central Asia, Kazaks have mainly inhabited the steppe zone from the Altay Mountains in the East to the Caspian Sea in the West. Fine scale characterization of the genetic profile and population structure of Kazaks would be invaluable for understanding their population history and modeling prehistoric human expansions across the Eurasian steppes. With this mind, we characterized the maternal lineages of 200 Kazaks from Jetisuu at mitochondrial genome level. Our results reveal that Jetisuu Kazaks have unique mtDNA haplotypes including those belonging to the basal branches of both West Eurasian (R0, H, HV) and East Eurasian (A, B, C, D) lineages. The great diversity observed in their maternal lineages may reflect pivotal geographic location of Kazaks in Eurasia and implies a complex history for this population. Comparative analyses of mitochondrial genomes of human populations in Central Eurasia reveal a common maternal genetic ancestry for Turko-Mongolian speakers and their expansion being responsible for the presence of East Eurasian maternal lineages in Central Eurasia. Our analyses further indicate maternal genetic affinity between the Sherpas from the Tibetan Plateau with the Turko-Mongolian speakers.

Helicobacter pylori genomes reveal Paleolithic human migration to the east end of Asia.

A virulence bacterium, Helicobacter pylori, evolved parallel to its host human, therefore, can work as a marker for tracing the human migration. We found H. pylori strains indigenous in the southernmost islands of Japanese Archipelago, Okinawa, and defined them as hspOkinawa and hpRyukyu. Genome data of the strains revealed that hspOkinawa diverged from other East Asian strains about 20,000 years ago, and that hpRyukyu diverged about 45,000 years ago. The closest strains of hpRyukyu were found from Afghanistan, Punjab, and Nepal, which suggest this strain originated in the central Asia and traveled across the Eurasian continent during Paleolithic era. The divergence date of hpRyukyu corresponds with human fossil records in Okinawa. Although it is controversial from human DNA analyses whether descendants of the Paleolithic migrants remain in the modern Japanese population, this study reveals that the bacterium of Paleolithic origin remains in the stomachs of current Japanese.

Inferring intelligence of ancient people based on modern genomic studies.

Quantification of ancient human intelligence has become possible with recent advances in polygenic prediction. Intelligence is a complex trait that has both environmental and genetic components and high heritability. Large-scale genome-wide association studies based on ~270,000 individuals have demonstrated highly significant single-nucleotide polymorphisms (SNPs) associated with intelligence in present-day humans. We utilized those previously reported 12,037 SNPs to estimate a genetic component of intelligence in ancient Funadomari Jomon individual from 3700 years BP as well as four individuals of Afanasievo nuclear family from about 4100 years BP and who are considered anatomically modern humans. We have demonstrated that ancient individuals could have been not inferior in intelligence compared to present-day humans through assessment of the genetic component of intelligence. We have also confirmed that alleles associated with intelligence tend to spread equally between ancestral and derived origin suggesting that intelligence may be a neutral trait in human evolution.

Insights into Mus musculus Population Structure across Eurasia Revealed by Whole-Genome Analysis.

For more than 100 years, house mice (Mus musculus) have been used as a key animal model in biomedical research. House mice are genetically diverse, yet their genetic background at the global level has not been fully understood. Previous studies have suggested that they originated in South Asia and diverged into three major subspecies, almost simultaneously, approximately 110,000-500,000 years ago; however, they have spread across the world with the migration of modern humans in prehistoric and historic times (∼10,000 years ago to the present day) and have undergone secondary contact, which has complicated the genetic landscape of wild house mice. In this study, we sequenced the whole-genome sequences of 98 wild house mice collected from Eurasia, particularly East Asia, Southeast Asia, and South Asia. Although wild house mice were found to consist of three major genetic groups corresponding to the three major subspecies, individuals representing admixtures between subspecies were more prevalent in East Asia than has been previously recognized. Furthermore, several samples exhibited an incongruent pattern of genealogies between mitochondrial and autosomal genomes. Using samples that likely retained the original genetic components of subspecies with the least admixture, we estimated the pattern and timing of divergence among the subspecies. The estimated divergence time of the three subspecies was 187,000-226,000 years ago. These results will help us to understand the genetic diversity of wild mice on a global scale, and the findings will be particularly useful in future biomedical and evolutionary studies involving laboratory mice established from such wild mice.

Allelic and haplotypic HLA diversity in indigenous Malaysian populations explored using Next Generation Sequencing.

The heterogenous population of Malaysia includes more than 50 indigenous groups, and characterizing their HLA diversity would not only provide insights to their ancestry, but also on the effects of natural selection on their genome. We utilized hybridization-based sequence capture and short-read sequencing on the HLA region of 172 individuals representing seven indigenous groups in Malaysia (Jehai, Kintaq, Temiar, Mah Meri, Seletar, Temuan, Bidayuh). Allele and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1 revealed several ancestry-informative markers. Using SNP-based heterozygosity and pairwise Fst, we observed signals of natural selection, particularly in HLA-A, -C and -DPB1 genes. Consequently, we showed the impact of natural selection on phylogenetic inference using HLA and non-HLA SNPs. We demonstrate the utility of Next Generation Sequencing for generating unambiguous, high-throughput, high-resolution HLA data that adds to our knowledge of HLA diversity and natural selection in indigenous minority groups.

Corrigendum: Possible roles for the hominoid-specific DSCR4 gene in human cells [Genes Genet. Syst. (2021) 96, p. 1-11].

Legends to Figures 4 and 5 (p. 7) should be exchanged. Below are the correct legends to Figure 4 and Figure 5. Fig. 4. Interconnection of DSCR4 overexpression-mediated perturbed pathways. KEGG analysis of DSCR4 overexpression-mediated DEGs shows enrichment for the tightly interconnected pathways of the coagulation cascade and the complement cascade (highlighted in red) and further confirm the connection of these cascades with cell adhesion, migration and proliferation (red circle). Fig. 5. Expression profile of DSCR4 across human cell lines and tissues. According to Roadmap Epigenomics Project data, DSCR4 and DSCR8, which share a bidirectional promoter, are highly expressed only in K562 cells, a type of leukemia cell. Analysis of transcriptome data provided by Prescott et al. (2015) showed that DSCR4 and DSCR8 also display high expression in human and chimpanzee neural crest cells, which are critical migratory cells involved in facial morphogenesis in the embryo. (1) Data from Prescott et al. (2015). (2) Samples also include esophagus, lung, spleen and fetal large intestine. (3) Samples also include brain germinal matrix, hippocampus, fetal small intestine, stomach, left ventricle, small intestine, sigmoid colon, HEPG2 cells and HMEC cells. The PDF file for DOI: https://doi.org/10.1266/ggs.20-00012 has been replaced with the corrected version as of June 17, 2021.

Possible roles for the hominoid-specific DSCR4 gene in human cells.

Down syndrome in humans is caused by trisomy of chromosome 21. DSCR4 (Down syndrome critical region 4) is a de novo-originated protein-coding gene present only in human chromosome 21 and its homologous chromosomes in apes. Despite being located in a medically critical genomic region and an abundance of evidence indicating its functionality, the roles of DSCR4 in human cells are unknown. We used a bioinformatic approach to infer the biological importance and cellular roles of this gene. Our analysis indicates that DSCR4 is likely involved in the regulation of interconnected biological pathways related to cell migration, coagulation and the immune system. We also showed that these predicted biological functions are consistent with tissue-specific expression of DSCR4 in migratory immune system leukocyte cells and neural crest cells (NCCs) that shape facial morphology in the human embryo. The immune system and NCCs are known to be affected in Down syndrome individuals, who suffer from DSCR4 misregulation, which further supports our findings. Providing evidence for the critical roles of DSCR4 in human cells, our findings establish the basis for further experimental investigations that will be necessary to confirm the roles of DSCR4 in the etiology of Down syndrome.

Genome-wide SNP data of Izumo and Makurazaki populations support inner-dual structure model for origin of Yamato people.

The "Dual Structure" model on the formation of the modern Japanese population assumes that the indigenous hunter-gathering population (symbolized as Jomon people) admixed with rice-farming population (symbolized as Yayoi people) who migrated from the Asian continent after the Yayoi period started. The Jomon component remained high both in Ainu and Okinawa people who mainly reside in northern and southern Japan, respectively, while the Yayoi component is higher in the mainland Japanese (Yamato people). The model has been well supported by genetic data, but the Yamato population was mostly represented by people from Tokyo area. We generated new genome-wide SNP data using Japonica Array for 45 individuals in Izumo City of Shimane Prefecture and for 72 individuals in Makurazaki City of Kagoshima Prefecture in Southern Kyushu, and compared these data with those of other human populations in East Asia, including BioBank Japan data. Using principal component analysis, phylogenetic network, and f4 tests, we found that Izumo, Makurazaki, and Tohoku populations are slightly differentiated from Kanto (including Tokyo), Tokai, and Kinki regions. These results suggest the substructure within Mainland Japanese maybe caused by multiple migration events from the Asian continent following the Jomon period, and we propose a modified version of "Dual Structure" model called the "Inner-Dual Structure" model.

dbCNS: A New Database for Conserved Noncoding Sequences.

We developed dbCNS (http://yamasati.nig.ac.jp/dbcns), a new database for conserved noncoding sequences (CNSs). CNSs exist in many eukaryotes and are assumed to be involved in protein expression control. Version 1 of dbCNS, introduced here, includes a powerful and precise CNS identification pipeline for multiple vertebrate genomes. Mutations in CNSs may induce morphological changes and cause genetic diseases. For this reason, many vertebrate CNSs have been identified, with special reference to primate genomes. We integrated ∼6.9 million CNSs from many vertebrate genomes into dbCNS, which allows users to extract CNSs near genes of interest using keyword searches. In addition to CNSs, dbCNS contains published genome sequences of 161 species. With purposeful taxonomic sampling of genomes, users can employ CNSs as queries to reconstruct CNS alignments and phylogenetic trees, to evaluate CNS modifications, acquisitions, and losses, and to roughly identify species with CNSs having accelerated substitution rates. dbCNS also produces links to dbSNP for searching pathogenic single-nucleotide polymorphisms in human CNSs. Thus, dbCNS connects morphological changes with genetic diseases. A test analysis using 38 gnathostome genomes was accomplished within 30 s. dbCNS results can evaluate CNSs identified by other stand-alone programs using genome-scale data.

House mouse Mus musculus dispersal in East Eurasia inferred from 98 newly determined complete mitochondrial genome sequences.

The Eurasian house mouse Mus musculus is useful for tracing prehistorical human movement related to the spread of farming. We determined whole mitochondrial DNA (mtDNA) sequences (ca. 16,000 bp) of 98 wild-derived individuals of two subspecies, M. m. musculus (MUS) and M. m. castaneus (CAS). We revealed directional dispersals reaching as far as the Japanese Archipelago from their homelands. Our phylogenetic analysis indicated that the eastward movement of MUS was characterised by five step-wise regional extension events: (1) broad spatial expansion into eastern Europe and the western part of western China, (2) dispersal to the eastern part of western China, (3) dispersal to northern China, (4) dispersal to the Korean Peninsula and (5) colonisation and expansion in the Japanese Archipelago. These events were estimated to have occurred during the last 2000-18,000 years. The dispersal of CAS was characterised by three events: initial divergences (ca. 7000-9000 years ago) of haplogroups in northernmost China and the eastern coast of India, followed by two population expansion events that likely originated from the Yangtze River basin to broad areas of South and Southeast Asia, including Sri Lanka, Bangladesh and Indonesia (ca. 4000-6000 years ago) and to Yunnan, southern China and the Japanese Archipelago (ca. 2000-3500). This study provides a solid framework for the spatiotemporal movement of the human-associated organisms in Holocene Eastern Eurasia using whole mtDNA sequences, reliable evolutionary rates and accurate branching patterns. The information obtained here contributes to the analysis of a variety of animals and plants associated with prehistoric human migration.

Nucleotide sequencing of the HoxA gene cluster using Gorilla fosmid clones.

We sequenced the western gorilla (Gorilla gorilla) HoxA cluster region using seven fosmid clones, and found that the total tiling path sequence was 214,185 bp from the 5' non-genic region of HoxA1 to the 3' non-genic region of Evx1. We compared the nucleotide sequence with the gorilla genome sequence in the NCBI database, and the overall proportion of nucleotide difference was estimated to be 0.0005-0.0007. These estimates are lower than overall genomic polymorphism in gorillas.

The Dynamics, Causes, and Impacts of Mammalian Evolutionary Rates Revealed by the Analyses of Capybara Draft Genome Sequences.

Capybara (Hydrochoerus hydrochaeri) is the largest species among the extant rodents. The draft genome of capybara was sequenced with the estimated genome size of 2.6 Gb. Although capybara is about 60 times larger than guinea pig, comparative analyses revealed that the neutral evolutionary rates of the two species were not substantially different. However, analyses of 39 mammalian genomes revealed very heterogeneous evolutionary rates. The highest evolutionary rate, 8.5 times higher than the human rate, was found in the Cricetidae-Muridae common ancestor after the divergence of Spalacidae. Muridae, the family with the highest number of species among mammals, emerged after the rate acceleration. Factors responsible for the evolutionary rate heterogeneity were investigated through correlations between the evolutionary rate and longevity, gestation length, litter frequency, litter size, body weight, generation interval, age at maturity, and taxonomic order. The regression analysis of these factors showed that the model with three factors (taxonomic order, generation interval, and litter size) had the highest predictive power (R2 = 0.74). These three factors determine the number of meiosis per unit time. We also conducted transcriptome analysis and found that the evolutionary rate dynamics affects the evolution of gene expression patterns.

Genome-wide diversity and global migration patterns in dromedaries follow ancient caravan routes.

Dromedaries have been essential for the prosperity of civilizations in arid environments and the dispersal of humans, goods and cultures along ancient, cross-continental trading routes. With increasing desertification their importance as livestock species is rising rapidly, but little is known about their genome-wide diversity and demographic history. As previous studies using few nuclear markers found weak phylogeographic structure, here we detected fine-scale population differentiation in dromedaries across Asia and Africa by adopting a genome-wide approach. Global patterns of effective migration rates revealed pathways of dispersal after domestication, following historic caravan routes like the Silk and Incense Roads. Our results show that a Pleistocene bottleneck and Medieval expansions during the rise of the Ottoman empire have shaped genome-wide diversity in modern dromedaries. By understanding subtle population structure we recognize the value of small, locally adapted populations and appeal for securing genomic diversity for a sustainable utilization of this key desert species.

Genetic diversity of different breeds of Kazakh sheep using microsatellite analysis.

A total of 75 individuals from five sheep populations in Kazakhstan were investigated based on 12 STR (short tandem repeat, also known as microsatellite) markers in order to study their genetic structure and phylogenetic relationship based on genetic distances. These sheep had a high level of genetic diversity. In total, 163 alleles were found in all the populations using 12 microsatellite loci. The mean number of alleles, effective number of alleles, and polymorphism information content (PIC) values per loci were 13.4, 5.9, and 0.78, respectively. Comparing the allelic diversity between the populations, the highest genetic diversity was observed in the Edilbay-1 sheep breed ( 8.333 ± 0.644 ), and the lowest parameter was for Kazakh Arkhar-Merino ( 7.083 ± 0.633 ). In all populations, there is a deficiency of heterozygosity. The largest genetic diversity was found in loci INRA023 and CSRD247 with 16 alleles, and the smallest polymorphism was noted for the locus D5S2 with 8 alleles. The level of observed heterozygosity was in the range 0.678 ± 0.051 for Kazakh Arkhar-Merino and 0.767 ± 0.047 for Kazakh fat-tailed coarse wool. The expected heterozygosity level range was from 0.702 ± 0.033 for Kazakh Arkhar-Merino to 0.777 ± 0.023 for Edilbay-1. When 12 microsatellite loci are compared, the OarFCB20 locus showed the highest level of genetic variability. Excess of heterozygosity was observed at three loci; MAF065, McM042, and OarFCB20. The highest genetic distance was observed between Kazakh Arkhar-Merino and Edilbay-1, whereas the genetic distance between Edilbay-1 and Edilbay-2 is the smallest using Nei's standard genetic distance. The Edilbay-1 sheep breed possesses the largest genetic diversity among these five populations.

Chance, Finiteness, and History.

Importance of chance, finiteness, and history in evolution is pointed out with special reference to the neutral theory.

Draft genome sequence of Japanese wood mouse, Apodemus speciosus.

The wood mouse (genus Apodemus) is one of the most common rodents in broad-leaf forests in the temperate zone of the Palaearctic region. Molecular studies of wood mice have critically enhanced the understanding of their evolution and ancestral biogeographic events. However, their molecular data are currently only limited to partial mitochondrial sequences and a few genes. Therefore, we sequenced the wood mouse genome to facilitate the acquisition of useful resources for inferring their molecular evolution. We sampled a wild wood mouse at Tsukuba, Japan, and sequenced its whole-genome using the Illumina Hiseq. 2000. To reduce the risk of non-randomness, three paired-end libraries (insert sizes: 150, 300, and 500 bp) and, two mate-pair reads (insert sizes: 8 and 20 kbp) were constructed. In total, we generated approximately 210 Gbp data. From these sequences, we reconstructed 336,124 scaffolds. These data will enhance our understanding of the evolution and ecological factors that affect their genetic constitution. The genome scaffolds generated are available in the National Center Biotechnology Information (NCBI) BioProject with accession number PRJDB5914.

Discerning the Origins of the Negritos, First Sundaland People: Deep Divergence and Archaic Admixture.

Human presence in Southeast Asia dates back to at least 40,000 years ago, when the current islands formed a continental shelf called Sundaland. In the Philippine Islands, Peninsular Malaysia, and Andaman Islands, there exist indigenous groups collectively called Negritos whose ancestry can be traced to the "First Sundaland People." To understand the relationship between these Negrito groups and their demographic histories, we generated genome-wide single nucleotide polymorphism data in the Philippine Negritos and compared them with existing data from other populations. Phylogenetic tree analyses show that Negritos are basal to other East and Southeast Asians, and that they diverged from West Eurasians at least 38,000 years ago. We also found relatively high traces of Denisovan admixture in the Philippine Negritos, but not in the Malaysian and Andamanese groups, suggesting independent introgression and/or parallel losses involving Denisovan introgressed regions. Shared genetic loci between all three Negrito groups could be related to skin pigmentation, height, facial morphology and malarial resistance. These results show the unique status of Negrito groups as descended from the First Sundaland People.

Silencing Effect of Hominoid Highly Conserved Noncoding Sequences on Embryonic Brain Development.

Superfamily Hominoidea, which consists of Hominidae (humans and great apes) and Hylobatidae (gibbons), is well-known for sharing human-like characteristics, however, the genomic origins of these shared unique phenotypes have mainly remained elusive. To decipher the underlying genomic basis of Hominoidea-restricted phenotypes, we identified and characterized Hominoidea-restricted highly conserved noncoding sequences (HCNSs) that are a class of potential regulatory elements which may be involved in evolution of lineage-specific phenotypes. We discovered 679 such HCNSs from human, chimpanzee, gorilla, orangutan and gibbon genomes. These HCNSs were demonstrated to be under purifying selection but with lineage-restricted characteristics different from old CNSs. A significant proportion of their ancestral sequences had accelerated rates of nucleotide substitutions, insertions and deletions during the evolution of common ancestor of Hominoidea, suggesting the intervention of positive Darwinian selection for creating those HCNSs. In contrary to enhancer elements and similar to silencer sequences, these Hominoidea-restricted HCNSs are located in close proximity of transcription start sites. Their target genes are enriched in the nervous system, development and transcription, and they tend to be remotely located from the nearest coding gene. Chip-seq signals and gene expression patterns suggest that Hominoidea-restricted HCNSs are likely to be functional regulatory elements by imposing silencing effects on their target genes in a tissue-restricted manner during fetal brain development. These HCNSs, emerged through adaptive evolution and conserved through purifying selection, represent a set of promising targets for future functional studies of the evolution of Hominoidea-restricted phenotypes.

A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan.

The Jomon period of the Japanese Archipelago, characterized by cord-marked 'jomon' potteries, has yielded abundant human skeletal remains. However, the genetic origins of the Jomon people and their relationships with modern populations have not been clarified. We determined a total of 115 million base pair nuclear genome sequences from two Jomon individuals (male and female each) from the Sanganji Shell Mound (dated 3000 years before present) with the Jomon-characteristic mitochondrial DNA haplogroup N9b, and compared these nuclear genome sequences with those of worldwide populations. We found that the Jomon population lineage is best considered to have diverged before diversification of present-day East Eurasian populations, with no evidence of gene flow events between the Jomon and other continental populations. This suggests that the Sanganji Jomon people descended from an early phase of population dispersals in East Asia. We also estimated that the modern mainland Japanese inherited <20% of Jomon peoples' genomes. Our findings, based on the first analysis of Jomon nuclear genome sequence data, firmly demonstrate that the modern mainland Japanese resulted from genetic admixture of the indigenous Jomon people and later migrants.