Fractal genomics of SOD1 evolutionSaeed, Mohammad
doi: 10.1007/s00251-020-01184-4pmid: 33237378
To understand the fundamental processes of gene evolution such as the impact of point mutations and segmental duplications on statistical topography, superoxide dismutase-1 (SOD1) orthologous sequences (n = 50) are studied. These demonstrate scale invariant self-similarity patterns and long-range correlations (LRCs) indicating fractal organization. Phylogenetic hierarchies change when SOD1 orthologs are grouped according to fractal measures, indicating that statistical topographies can be used to study gene evolution. Sliding window k-mer analysis show that majority of k-mers across all SOD1 orthologs are unique, with very few duplications. Orthologs from simpler species contribute minimally (< 1% of k-mers) to more complex species. Both simple and complex random processes fail to produce significant matching k-mer sequences for SOD1 orthologs. Point mutations causing amyotrophic lateral sclerosis do not impact the fractal organization of human SOD1. Hence, SOD1 did not evolve by a patchwork of repetitive sequences modified by point mutations. Moreover, fractal and other methods described here can be used to study the origin and evolution of genomes.
Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon-inducible transmembrane 3 (IFITM3) gene, a susceptibility factor for pandemic 2009 H1N1 influenza A virusKim, Yong-Chan; Jeong, Byung-Hoon
doi: 10.1007/s00251-020-01188-0pmid: 33174121
The interferon-inducible transmembrane 3 (IFITM3) protein is an effector of the host innate immune system that shows defensive activity against a wide range of viruses, including the influenza A virus. Previous studies have reported that three transcription-related regulatory single nucleotide polymorphisms (SNPs), rs12252, rs34481144, and rs6598045, showed potent associations with the severity of pandemic influenza A 2009 infection and susceptibility to this virus, respectively. However, the distribution of the risk genotypes of these three SNPs according to ethnic background has remained elusive. In this study, we compared the genotype and allele frequencies of the IFITM3 polymorphisms among several ethnic groups including American, African, European, South Asian, and East Asian using chi-square test. In addition, we analyzed the worldwide distribution of risk genotypes for pandemic influenza A 2009 virus infection. We found that the genotype and allele distributions of the rs12252, rs34481144, and rs6598045 SNPs were significantly different among several ethnic groups. In addition, the risk genotypes of the IFITM3 polymorphisms were also significantly different worldwide. To the best of our knowledge, this was the first simultaneous estimation of the risk genotypes of the IFITM3 gene with respect to pandemic influenza A 2009 virus infection.
Evolution of HLA-F and its orthologues in primate species: a complex tale of conservation, diversification and inactivationOtting, N.; de Groot, N. G.; Bontrop, R. E.
doi: 10.1007/s00251-020-01187-1pmid: 33184728
HLA-F represents one of the nonclassical MHC class I molecules in humans. Its main characteristics involve low levels of polymorphism in combination with a restricted tissue distribution. This signals that the gene product executes a specialised function, which, however, is still poorly understood. Relatively little is known about the evolutionary equivalents of this gene in nonhuman primates, especially with regard to population data. Here we report a comparative genetic analysis of the orthologous genes of HLA-F in various great ape, Old World monkey (OWM), and New World monkey (NWM) species. HLA-F-related transcripts were found in all subjects studied. Low levels of polymorphism were encountered, although the length of the predicted gene products may vary. In most species, one or two transcripts were discovered, indicating the presence of only one active F-like gene per chromosome. An exception was provided by a New World monkey species, namely, the common marmoset. In this species, the gene has been subject to duplication, giving rise to up to six F-like transcripts per animal. In humans, great apes, and OWM, and probably the majority of the NWM species, the evolutionary equivalents of the HLA-F gene experienced purifying selection. In the marmoset, however, the gene was initially duplicated, but the expansion was subjected afterwards to various mechanisms of genetic inactivation, as evidenced by the presence of pseudogenes and an array of genetic artefacts in a section of the transcripts.
Association of HLA-DQ and IL13 gene variants with challenge-proven shrimp allergy in West Bengal, IndiaLaha, Arghya; Ghosh, Amlan; Moitra, Saibal; Biswas, Himani; Saha, Nimai Chandra; Bhattacharya, Srijit; Saha, Goutam Kumar; Podder, Sanjoy
doi: 10.1007/s00251-020-01185-3pmid: 33175217
Little is known about genetic factors and mechanisms underlying shrimp allergy. Genome-wide association studies identified HLA class-II and IL13 genes as highly plausible candidates for shrimp allergy. The present study was designed to investigate potential associations of HLA-DQ rs9275596, IL13 rs20541, and IL13 rs1800925 polymorphisms with challenge-proven shrimp allergy using the data from 532 people of West Bengal, India; selected on basis of positive skin prick test, elevated specific IgE and medical history. Risk genotypes, i.e., HLA-DQ rs9275596 CC, IL13 rs20541 AA, and IL13 rs1800925 TT, were found to be significantly associated with challenge positive shrimp allergy (P = 0.04, 0.01, and 0.03, respectively). Distribution of genotypes for HLA-DQ and IL13 polymorphisms in allergic and control subjects showed significant difference between younger (20–40 years) and older (> 40 years) age group (P = 0.006). Risk genotypes significantly associated with elevated shrimp-specific IgE. IL13 TA haplotype significantly associated with shrimp allergy and elevated specific IgE (P = 0.02). Synergistic effect of IL13 TA haplotype–HLA-DQ rs9275596 CC genotype interaction significantly elevated specific IgE (P = 0.03). The present study suggests that HLA-DQ and IL13 polymorphisms pose major risk for shrimp allergic patients in West Bengal, India and thus could be helpful for early target-specific therapeutic intervention in near future.
High-throughput immunogenetic typing of koalas suggests possible link between MHC alleles and cancersQuigley, Bonnie L.; Tzipori, Galit; Nilsson, Karen; Timms, Peter
doi: 10.1007/s00251-020-01181-7pmid: 33083849
Characterizing the allelic diversity within major histocompatibility complex (MHC) genes is an important way of determining the potential genetic resilience of a population to infectious and ecological pressures. For the koala (Phascolarctos cinereus), endemic diseases, anthropogenic factors and climate change are all placing increased pressure on this vulnerable marsupial. To increase the ability of researchers to study MHC genetics in koalas, this study developed and tested a high-throughput immunogenetic profiling methodology for targeting MHC class I UA and UC genes and MHC class II DAB, DBB, DCB and DMB genes in a population of 82 captive koalas. This approach was validated by comparing the determined allelic profiles from 36 koala family units (18 dam-sire-joey units and 18 parent-joey pairs), finding 96% overall congruence within family profiles. Cancers are a significant cause of morbidity in koalas and the risk factors remain undetermined. Our analysis of this captive population revealed several novel MHC alleles, including a potential link between the DBB*03 allele and a risk of developing cancer. This method offers a reliable, high-throughput protocol for expanded study into koala immunogenetics.
Evidence for the loss of plasminogen receptor KT gene in chickenSharma, Sandhya; Shinde, Sagar Sharad; Teekas, Lokdeep; Vijay, Nagarjun
doi: 10.1007/s00251-020-01186-2pmid: 33247773
The loss of conserved genes has the potential to alter phenotypes drastically. Screening of vertebrate genomes for lineage-specific gene loss events has identified numerous natural knockouts associated with specific phenotypes. We provide evidence for the loss of a multi-exonic plasminogen receptor KT (PLGRKT) protein-encoding gene located on the Z chromosome in chicken. Exons 1 and 2 are entirely missing; remnants of exon 3 and a mostly intact exon 4 are identified in an assembly gap-free region in chicken with conserved synteny across species and verified using transcriptome and genome sequencing. PLGRKT gene disrupting changes are present in representative species from all five galliform families. In contrast to this, the presence of an intact transcriptionally active PLGRKT gene in species such as mallard, swan goose, and Anolis lizard suggests that gene loss occurred in the galliform lineage sometime between 68 and 80 Mya. The presence of galliform specific chicken repeat 1 (CR1) insertion at the erstwhile exon 2 of PLGRKT gene suggests repeat insertion-mediated loss. However, at least nine other independent PLGRKT coding frame disrupting changes in other bird species are supported by genome sequencing and indicate a role for relaxed purifying selection before CR1 insertion. The recurrent loss of a conserved gene with a role in the regulation of macrophage migration, efferocytosis, and blood coagulation is intriguing. Hence, we propose potential candidate genes that might be compensating the function of PLGRKT based on the presence of a C-terminal lysine residue, transmembrane domains, and gene expression patterns.