Incipient Parallel Evolution of SARS-CoV-2 Deltacron Variant in South Brazil.

With the coexistence of multiple lineages and increased international travel, recombination and gene flow are likely to become increasingly important in the adaptive evolution of SARS-CoV-2. These processes could result in genetic introgression and the incipient parallel evolution of multiple recombinant lineages. However, identifying recombinant lineages is challenging, and the true extent of recombinant evolution in SARS-CoV-2 may be underestimated. This study describes the first SARS-CoV-2 Deltacron recombinant case identified in Brazil. We demonstrate that the recombination breakpoint is at the beginning of the Spike gene. The 5' genome portion (circa 22 kb) resembles the AY.101 (Delta), and the 3' genome portion (circa 8 kb nucleotides) is most similar to the BA.1.1 (Omicron). Furthermore, evolutionary genomic analyses indicate that the new strain emerged after a single recombination event between lineages of diverse geographical locations in December 2021 in South Brazil. This Deltacron, AYBA-RS, is one of the dozens of recombinants described in 2022. The submission of only four sequences in the GISAID database suggests that this lineage had a minor epidemiological impact. However, the recent emergence of this and other Deltacron recombinant lineages (XD, XF, and XS) suggests that gene flow and recombination may play an increasingly important role in the COVID-19 pandemic. We explain the evolutionary and population genetic theory that supports this assertion, concluding that this stresses the need for continued genomic surveillance. This monitoring is vital for countries where multiple variants are present, as well as for countries that receive significant inbound international travel.

Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals.

Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe response to COVID-19. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the genetic predisposition to severe COVID-19 outcomes. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform a locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify four introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. Using reporter assays in the presence/absence of SARS-CoV-2, we find evidence that these variants respond to viral infection. These variants likely drive the locus' impact on severity by modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.

The negative impact of the hominin's DPP4 gene inherited from neanderthals to pandemic of COVID-19

Background: According to preliminary sequences from 2010, 99.7% of the nucleotide sequences of the modern human and Neanderthal genomes are identical, compared to humans sharing around 98.8% of sequences with the chimpanzee. In contrast, the difference between chimpanzees and modern humans is approximately 1,462 mtDNA base pairs. Materials and Methods: Neanderthal-inherited genetic material is found in all non-African populations and was initially reported to comprise 1 to 4% of the genome. This fraction was later refined to 1.5 to 2.1%. We had gone through many researches of Neanderthals affected gene flow in humans. Results: It is estimated that 20% of Neanderthal DNA currently survives in modern humans. Modern human genes involved in making keratin, a protein constituent of skin, hair, and nails, have especially high levels of introgression. For example, approximately 66% of East Asians contain a POUF23L variant introgressed from Neanderthals, while 70% of Europeans possess an introgressed allele of BNC2. Our finding shines a light on an enzyme called dipeptidyl peptidase4 (DPP4). Scientists already know the protein allows another coronavirus, which causes Middle Eastern respiratory syndrome (MERS), to bind to and enter human cells. The new analysis, of DPP4 gene variants among COVID-19 patients, suggests the enzyme also provides SARS-CoV-2 with a second door into our cells, along with its usual infection route via the angiotensin-converting enzyme 2 (ACE2) receptor on cell surfaces. Conclusion: Most Europeans, Asians, and Native Americans harbor a handful of genes from Neanderthals, up 1.8% to 2.6% of their DNA. Studies of ancient DNA in Neanderthal fossils have shown the hominin's DPP4 gene subtly differs from the typical human one. Conclusion: The hominin's DPP4 gene inherited from Neanderthals plays a major role in Immune System Disorders and Lower Immune response in many diseases. This gene plays a major role in affecting humans with COVID-19 and spreading it through the world. All humans contain this gene from 1 to 4%. East Asians, Europeans, Middle and south Americans conveys more, hence, native Africans contain less amounts of hominin's DPP4 gene. Therefore, East Asians, Europeans, Middle and south Americans are prone to severe COVID-19.

Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells.

Although some variation introgressed from Neanderthals has undergone selective sweeps, little is known about its functional significance. We used a Massively Parallel Reporter Assay (MPRA) to assay 5,353 high-frequency introgressed variants for their ability to modulate the gene expression within 170 bp of endogenous sequence. We identified 2,548 variants in active putative cis-regulatory elements (CREs) and 292 expression-modulating variants (emVars). These emVars are predicted to alter the binding motifs of important immune transcription factors, are enriched for associations with neutrophil and white blood cell count, and are associated with the expression of genes that function in innate immune pathways including inflammatory response and antiviral defense. We combined the MPRA data with other data sets to identify strong candidates to be driver variants of positive selection including an emVar that may contribute to protection against severe COVID-19 response. We endogenously deleted two CREs containing expression-modulation variants linked to immune function, rs11624425 and rs80317430, identifying their primary genic targets as ELMSAN1, and PAN2 and STAT2, respectively, three genes differentially expressed during influenza infection. Overall, we present the first database of experimentally identified expression-modulating Neanderthal-introgressed alleles contributing to potential immune response in modern humans.