Infectious diseases may have arrested the southward advance of microblades in Upper Palaeolithic East Asia.

An unsolved archaeological puzzle of the East Asian Upper Palaeolithic is why the southward expansion of an innovative lithic technology represented by microblades stalled at the Qinling-Huaihe Line. It has been suggested that the southward migration of foragers with microblades stopped there, which is consistent with ancient DNA studies showing that populations to the north and south of this line had differentiated genetically by 19 000 years ago. Many infectious pathogens are believed to have been associated with hominins since the Palaeolithic, and zoonotic pathogens in particular are prevalent at lower latitudes, which may have produced a disease barrier.

Role of error catastrophe in transmission ability of virus.

The role played by error catastrophe is explicitly taken into account in a mathematical formulation to analyze COVID-19 data. The idea is to combine the mathematical genetics formalism of the error catastrophe of mutations in virus gene loci with the standard model of epidemics, which lacks the explicit incorporation of the effect of mutation on the spreading of viruses. We apply this formalism to the case of SARS-CoV-2 virus.

Lower promoter activity of the ST8SIA2 gene has been favored in evolving human collective brains.

ST8SIA2 is an important molecule regulating expression of the phenotype involved in schizophrenia. Lowered promoter activity of the ST8SIA2 gene is considered to be protective against schizophrenia by conferring tolerance to psychosocial stress. Here, we examined the promoter-type composition of anatomically modern humans (AMHs) and archaic humans (AHs; Neanderthals and Denisovans), and compared the promoter activity at the population level (population promoter activity; PPA) between them.

Two-dimensional site frequency spectrum for detecting, classifying and dating incomplete selective sweeps.

The two-dimensional site frequency spectrum (2D SFS) was investigated to describe the intra-allelic variability (IAV) maintained within a derived allele (D) group that has undergone an incomplete selective sweep against an ancestral allele group. We observed that recombination certainly muddles the ancestral relationships of allelic lineages between the two allele groups; however, the 2D SFS reveals intriguing signatures of recombination as well as the genealogical structure of the D group, particularly the size of a mutation and the time to the most recent common ancestor (TMRCA). Coalescent simulations were performed to achieve powerful and robust 2D SFS-based statistics with special reference to accurate evaluation of IAV, significance of recombination effects, and distinction between hard and soft selective sweeps.

A new inference method for detecting an ongoing selective sweep.

A simple method was developed to detect signatures of ongoing selective sweeps in single nucleotide polymorphism (SNP) data. Based largely on the traditional site frequency spectrum (SFS), the method additionally incorporates linkage disequilibrium (LD) between pairs of SNP sites and uniquely represents both SFS and LD information as hierarchical "barcodes." This barcode representation allows the identification of a hitchhiking genomic region surrounding a putative target site of positive selection, or a core site.

Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia.

A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (CGC-type) has significantly reduced promoter activity.

Nonequilibrium Neutral Theory for Hitchhikers.

Selective sweep is a phenomenon of reduced variation at presumably neutrally evolving sites (hitchhikers) in the genome that is caused by the spread of a selected allele at a linked focal site, and is widely used to test for action of positive selection. Nonetheless, selective sweep may also provide an unprecedented opportunity for studying nonequilibrium properties of the neutral variation itself. We have demonstrated this possibility in relation to ancient selective sweep for modern human-specific changes and ongoing selective sweep for local population-specific changes.

Genomic structure and evolution of multigene families: "flowers" on the human genome.

We report the results of an extensive investigation of genomic structures in the human genome, with a particular focus on relatively large repeats (>50 kb) in adjacent chromosomal regions. We named such structures "Flowers" because the pattern observed on dot plots resembles a flower. We detected a total of 291 Flowers in the human genome.

Use of Cumulative Poisson Probability Distribution as an Estimator of the Recombination Rate in an Expanding Population: Example of the Macaca fascicularis Major Histocompatibility Complex.

We describe a method to estimate the rate of recombination per generation from the genotypes of a large individual sample of an expanding population, for which the founding event is dated. The approach is illustrated with an application to estimating the major histocompatibility complex (MHC) recombination rate in the Mauritian macaque population. We genotyped 750 macaques by means of 17 microsatellites across the MHC region and reconstructed the seven most frequent haplotypes assumed to represent the founding haplotypes (H(rec(0))) as well as the 31% recombinant haplotypes (H(rec(h))) resulting from a variable number "h" of recombinations between the founding haplotypes.

Evolutionary origin of peptidoglycan recognition proteins in vertebrate innate immune system.

Background: Innate immunity is the ancient defense system of multicellular organisms against microbial infection. The basis of this first line of defense resides in the recognition of unique motifs conserved in microorganisms, and absent in the host. Peptidoglycans, structural components of bacterial cell walls, are recognized by Peptidoglycan Recognition Proteins (PGRPs).

Frequent gene conversion events between the X and Y homologous chromosomal regions in primates.

Background: Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance) between the X and Y chromosomes, depending on the time of recombination arrest.

Divergence, demography and gene loss along the human lineage.

Genomic DNA sequences are an irreplaceable source for reconstructing the vanished past of living organisms. Based on updated sequence data, this paper summarizes our studies on species divergence time, ancient population size and functional loss of genes in the primate lineage leading to modern humans (Homo sapiens sapiens). The inter- and intraspecific comparisons of DNA sequences suggest that the human lineage experienced a rather severe bottleneck in the Middle Pleistocene, throughout which period the subdivided African population played a predominant role in shaping the genetic architecture of modern humans.

The origin and genetic variation of domestic chickens with special reference to junglefowls Gallus g. gallus and G. varius.

It is postulated that chickens (Gallus gallus domesticus) became domesticated from wild junglefowls in Southeast Asia nearly 10,000 years ago. Based on 19 individual samples covering various chicken breeds, red junglefowl (G. g.

Gene flow between species of Lake Victoria haplochromine fishes.

The haplochromine cichlid fishes of Lake Victoria (LV), East Africa, are a textbook example of adaptive radiation-a rapid divergence of multiple morphologically distinguishable forms from a few founding lineages. The forms are generally believed to constitute a "flock" of several hundred reproductively isolated species in a dozen or so genera. This belief has, until now, not been subjected to a test, however.

Evolutionary history of sex-linked mammalian amelogenin genes.

Amelogenin (AMEL) arose prior to the emergence of tetrapods and transposed into an intron of the Rho GTPase-activating protein 6 gene. In the mammalian lineage leading to eutherians, a pair of homologous autosomes with this nested gene structure fused with the then already differentiating sex chromosomes by suppressing homologous recombination. As sex-chromosomal differentiation extended to the fused region, a pair of homologous AMEL genes too differentiated from each other in two steps; first in the 5' region (the promoter region to transposon MER5 in intron 2) and second in the remaining 3' region.

An Alu retrotransposition-mediated deletion of CHD7 in a patient with CHARGE syndrome.

CHD7 mutations account for about 60-65% among more than 200 CHARGE syndrome cases. When rare whole gene deletion cases associated with chromosomal abnormalities are excluded, all mutations of CHD7 reported to date have been point mutations and small deletions and insertions, rather than exonic deletions. To test whether exonic deletions represent a common pathogenic mechanism, we assessed exon copy number by using a recently developed method, the multiplex PCR/liquid chromatography assay (MP/LC).

The origin and evolution of human ampliconic gene families and ampliconic structure.

Out of the nine male-specific gene families in the human Y chromosome amplicons, we investigate the origin and evolution of seven families for which gametologous and orthologous sequences are available. Proto-X/Y gene pairs in the original mammalian sex chromosomes played major roles in origins and gave rise to five gene families: XKRY, VCY, HSFY, RBMY, and TSPY. The divergence times between gametologous X- and Y-linked copies in these families are well correlated with the former X-chromosomal locations.

Further evidence for recombination between mouse hemoglobin beta b1 and b2 genes based on the nucleotide sequences of intron, UTR, and intergenic spacer regions.

Nucleotide sequences of the intron regions and UTRs (Untranslated regions) of the hemoglobin beta adult genes, b1 and b2, and of the intergenic spacer region were determined for mouse strains representing the d, p, and w1 hemoglobin haplotypes defined by protein electrophoretic analyses. The hypothesis of recombination of the b1 and b2 genes between the d and w1 haplotypes previously reported in the cDNA nucleotide sequences was confirmed by neighbor-joining analyses of the intron regions and UTRs within the b1 and b2 genes, suggesting that all of the structures of hemoglobin beta adult genes support the hypothesis that the p haplotype was established by hybridization between d and w1 haplotype mice. The resultant recombinant of the p haplotype was found to have a d-like b1 gene and a w1-like b2 gene.

Origin and evolution of processed pseudogenes that stabilize functional Makorin1 mRNAs in mice, primates and other mammals.

We investigate the origin and evolution of a mouse processed pseudogene, Makorin1-p1, whose transcripts stabilize functional Makorin1 mRNAs. It is shown that Makorin1-p1 originated almost immediately before the musculus and cervicolor species groups diverged from each other some 4 million years ago and that the Makorin1-p1 orthologs in various Mus species are transcribed. However, Mus caroli in the cervicolor species group expresses not only Makorin1-p1, but also another older Makorin1-derived processed pseudogene, demonstrating the rapid generation and turnover in subgenus Mus.

Fixation of the human-specific CMP-N-acetylneuraminic acid hydroxylase pseudogene and implications of haplotype diversity for human evolution.

The human CMP-N-acetylneuraminic acid hydroxylase gene (CMAH) suffered deletion of an exon that encodes an active center for the enzyme approximately 3.2 million years ago (MYA). We analyzed a 7.

Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates.

Since the process of becoming dead genes or pseudogenes (pseudogenization) is irreversible and can occur rather rapidly under certain environmental circumstances, it is one plausible determinant for characterizing species specificity. To test this evolutionary hypothesis, we analyzed the tempo and mode of duplication and pseudogenization of bitter taste receptor (T2R) genes in humans as well as in 12 nonhuman primates. The results show that primates have accumulated more pseudogenes than mice after their separation from the common ancestor and that lineage-specific pseudogenization becomes more conspicuous in humans than in nonhuman primates.

Origins of mouse inbred strains deduced from whole-genome scanning by polymorphic microsatellite loci.

Microsatellite loci are uniformly distributed at approximately 100-kbp intervals on all chromosomes except the chromosome Y, and genetic information about more than 9000 loci and high-throughput polymorphism analysis are now available. Taking advantage of these properties, we carried out whole-genome scanning using eight common inbred strains (CIS) of laboratory mice, including A/J, C57BL/6J, CBA/J, DBA/2J, SM/J, SWR/J, NC/Nga, and 129/SvJ, and eight wild-derived inbred strains (WIS), BGL2/Ms, CAST/Ei, JF1/Ms, MSM/Ms, NJL/Ms, PGN2/Ms, SK/CamEi, and SWN/Ms. We selected and located 1226 informative loci at 1.

The phylogenetic relationship of tetrapod, coelacanth, and lungfish revealed by the sequences of forty-four nuclear genes.

The origin of tetrapods is a major outstanding issue in vertebrate phylogeny. Each of the three possible principal hypotheses (coelacanth, lungfish, or neither being the sister group of tetrapods) has found support in different sets of data. In an attempt to resolve the controversy, sequences of 44 nuclear genes encoding amino acid residues at 10,404 positions were obtained and analyzed.