Origin and diffusion of human Y chromosome haplogroup J1-M267

Human Y chromosome haplogroup J1-M267 is a common male lineage in West Asia. One high-frequency region—encompassing the Arabian Peninsula, southern Mesopotamia, and the southern Levant—resides ~ 2000 km away from the other one found in the Caucasus. The region between them, although has a lower frequency, nevertheless demonstrates high genetic diversity. Studies associate this haplogroup with the spread of farming from the Fertile Crescent to Europe, the spread of mobile pastoralism in the desert regions of the Arabian Peninsula, the history of the Jews, and the spread of Islam. Here, we study past human male demography in West Asia with 172 high-coverage whole Y chromosome sequences and 889 genotyped samples of haplogroup J1-M267. We show that this haplogroup evolved ~ 20,000 years ago somewhere in northwestern Iran, the Caucasus, the Armenian Highland, and northern Mesopotamia. The major branch—J1a1a1-P58—evolved during the early Holocene ~ 9500 years ago somewhere in the Arabian Peninsula, the Levant, and southern Mesopotamia. Haplogroup J1-M267 expanded during the Chalcolithic, the Bronze Age, and the Iron Age. Most probably, the spread of Afro-Asiatic languages, the spread of mobile pastoralism in the arid zones, or both of these events together explain the distribution of haplogroup J1-M267 we see today in the southern regions of West Asia.

Candidate SNP-markers altering TBP binding affinity for promoters of the Y-linked genes CDY2A, SHOX, and ZFY are lowering many indexes of reproductive potential in men

Reproductive potential is the most important conditional indicator reflecting the ability of individuals in a population to reproduce, survive and develop under optimal environmental conditions. As for humans, the concept of reproductive potential can include the level of the individual’s mental and physical state, which allows them to reproduce healthy offspring when they reach social and physical maturity. Female reproductive potential has been investigated in great detail, whereas the male reproductive potential (MRP) has not received the equal amount of attention as yet. Therefore, here we focused on the human Y chromosome and found candidate single-nucleotide polymorphism (SNP) markers of MRP. With our development named Web-service SNP_TATA_Z-tester, we examined in silico all 35 unannotated SNPs within 70-bp proximal promoters of the three Y-linked genes, CDY2A, SHOX and ZFY, which represent all types of human Y-chromosome genes, namely: unique, pseudo-autosomal, and human X-chromosome gene paralogs, respectively. As a result, we found 11 candidate SNP markers for MRP, which can significantly alter the TATA-binding protein (TBP) binding affinity for promoters of these genes. First of all, we selectively verified in vitro the values of the TBP-promoter affinity under this study, Pearson’s linear correlation between predicted and measured values of which were r = 0.94 (significance p < 0.005). Next, as a discussion, using keyword search tools of the PubMed database, we found clinically proven physiological markers of human pathologies, which correspond to a change in the expression of the genes carrying the candidate SNP markers predicted here. These were markers for spermatogenesis disorders (ZFY: rs1388535808 and rs996955491), for male maturation arrest (CDY2A: rs200670724) as well as for disproportionate short stature at Madelung deformity (e. g., SHOX: rs1452787381) and even for embryogenesis disorders (e. g., SHOX: rs28378830). This indicates a wide range of MRI indicators, alterations in which should be expected in the case of SNPs in the promoters of the human Y-chromosome genes and which can go far beyond changes in male fertility.

The Y Chromosome: A Complex Locus for Genetic Analyses of Complex Human Traits

The Human Y chromosome (ChrY) has been demonstrated to be a powerful tool for phylogenetics, population genetics, genetic genealogy and forensics. However, the importance of ChrY genetic variation in relation to human complex traits is less clear. In this review, we summarise existing evidence about the inherent complexities of ChrY variation and their use in association studies of human complex traits. We present and discuss the specific particularities of ChrY genetic variation, including Y chromosomal haplogroups, that need to be considered in the design and interpretation of genetic epidemiological studies involving ChrY.

aYChr-DB: a database of ancient human Y haplogroups

Ancient Y-Chromosomal DNA is an invaluable tool for dating and discerning the origins of migration routes and demographic processes that occurred thousands of years ago. Driven by the adoption of high-throughput sequencing and capture enrichment methods in paleogenomics, the number of published ancient genomes has nearly quadrupled within the last three years (2018–2020). Whereas ancient mtDNA haplogroup repositories are available, no similar resource exists for ancient Y-Chromosomal haplogroups. Here, we present aYChr-DB—a comprehensive collection of 1797 ancient Eurasian human Y-Chromosome haplogroups ranging from 44 930 BC to 1945 AD. We include descriptors of age, location, genomic coverage and associated archaeological cultures. We also produced a visualization of ancient Y haplogroup distribution over time. The aYChr-DB database is a valuable resource for population genomic and paleogenomic studies.

Disruptive natural selection by male reproductive potential prevents underexpression of protein-coding genes on the human Y chromosome as a self-domestication syndrome

Background In population ecology, the concept of reproductive potential denotes the most vital indicator of chances to produce and sustain a healthy descendant until his/her reproductive maturity under the best conditions. This concept links quality of life and longevity of an individual with disease susceptibilities encoded by his/her genome. Female reproductive potential has been investigated deeply, widely, and comprehensively in the past, but the male one has not received an equal amount of attention. Therefore, here we focused on the human Y chromosome and found candidate single-nucleotide polymorphism (SNP) markers of male reproductive potential. Results Examining in silico (i.e., using our earlier created Web-service SNP_TATA_Z-tester) all 1206 unannotated SNPs within 70 bp proximal promoters of all 63 Y-linked genes, we found 261 possible male-reproductive-potential SNP markers that can significantly alter the binding affinity of TATA-binding protein (TBP) for these promoters. Among them, there are candidate SNP markers of spermatogenesis disorders (e.g., rs1402972626), pediatric cancer (e.g., rs1483581212) as well as male anxiety damaging family relationships and mother’s and children’s health (e.g., rs187456378). First of all, we selectively verified in vitro both absolute and relative values of the analyzed TBP–promoter affinity, whose Pearson’s coefficients of correlation between predicted and measured values were r = 0.84 (significance p < 0.025) and r = 0.98 (p < 0.025), respectively. Next, we found that there are twofold fewer candidate SNP markers decreasing TBP–promoter affinity relative to those increasing it, whereas in the genome-wide norm, SNP-induced damage to TBP–promoter complexes is fourfold more frequent than SNP-induced improvement (p < 0.05, binomial distribution). This means natural selection against underexpression of these genes. Meanwhile, the numbers of candidate SNP markers of an increase and decrease in male reproductive potential were indistinguishably equal to each other (p < 0.05) as if male self-domestication could have happened, with its experimentally known disruptive natural selection. Because there is still not enough scientific evidence that this could have happened, we discuss the human diseases associated with candidate SNP markers of male reproductive potential that may correspond to domestication-related disorders in pets. Conclusions Overall, our findings seem to support a self-domestication syndrome with disruptive natural selection by male reproductive potential preventing Y-linked underexpression of a protein.

SHIMS 3.0: Highly efficient single-haplotype iterative mapping and sequencing using ultra-long nanopore reads

The reference sequence of structurally complex regions can only be obtained through a highly accurate clone-based approach that we call Single-Haplotype Iterative Mapping and Sequencing (SHIMS). In recent years, improvements to SHIMS have reduced the cost and time required by two orders of magnitude, but internally repetitive clones still require extensive manual effort to transform draft assemblies into reference-quality finished sequences. Here we introduce SHIMS 3.0, using ultra-long nanopore reads to resolve internally repetitive structures and minimize the need for manual finishing of Illumina-based draft assemblies. This protocol proceeds from clone-picking to finished assemblies in 2 weeks for about 80 dollars per clone. We have used SHIMS 3.0 to finish the structurally complex TSPY array on the human Y chromosome, which could not be resolved by previous sequencing methods. Our protocol provides access to structurally complex regions that would otherwise be inaccessible from whole-genome shotgun data or require an impractical amount of manual effort to generate an accurate assembly.