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Latest Advances in Comparative Genomics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Informatics".

Deadline for manuscript submissions: closed (20 October 2025) | Viewed by 4226

Special Issue Editor

Dr. Candice Brinkmeyer-Langford

E-Mail Website
Guest Editor
Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA
Interests: genetics/genomics; roles of genetic diversity in neurodegenerative diseases; gene x environment interactions in diseases; virus-induced neurological conditions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Comparative genomic studies reveal similarities and fundamental differences between species, thus providing important insights into the evolution and distinguishing aspects of different species. Over half a century ago, Susumo Ohno postulated that genomic duplication contributed to genomic evolution, and subsequent technological advancements in gene mapping and sequencing have enabled ever higher-resolution perspectives of genomic evolution. In the last 20 years, sequence alignment and phylogenetic reconstruction have become well-established tools of comparative genomics. Today, comparative genomics has been applied to many fields ranging from agriculture to zoology, using advanced and/or discipline-specific software tools and resources.

The prime goal for this Special Issue of International Journal of Molecular Sciences is to spotlight novel research relevant to the field of comparative genomics. Basic, translational, and computational research studies, as well as studies using new, paradigm-shifting methods, are encouraged.

Dr. Candice Brinkmeyer-Langford
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • genetics
  • genomics
  • evolution
  • phylogeny
  • sequencing
  • variation
  • conservation

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Published Papers (4 papers)

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Research

13 pages, 2567 KB  
Article
Multidimensional Gene Space as an Approach for Analyzing the Organization of Genomes
by Konstantin Zaytsev, Natalya Bogatyreva and Alexey Fedorov
Int. J. Mol. Sci. 2025, 26(24), 11926; https://doi.org/10.3390/ijms262411926 - 10 Dec 2025
Viewed by 213
Abstract
Genomic organization and its comparative analysis throughout all major kingdoms of life are extensively studied across multiple scales, ranging from individual gene-level analyses to system-wide investigations. This work introduces a novel framework for characterizing genetic architecture through a new integral genomic parameter. We [...] Read more.
Genomic organization and its comparative analysis throughout all major kingdoms of life are extensively studied across multiple scales, ranging from individual gene-level analyses to system-wide investigations. This work introduces a novel framework for characterizing genetic architecture through a new integral genomic parameter. We propose the concept of a multidimensional Gene Space to enable holistic quantification of genome organization principles. Gene Space—a multidimensional space based on the frequencies of nucleotide tokens, such as individual nucleotides, codons, or codon pairs. We demonstrate that in this space, genes from each of the studied microorganism species occupy a limited region, and individual genes from different species can be effectively separated with more than 95% accuracy. Consequently, a specific Genome Subspace can be defined for each species, which constrains the organism’s evolutionary pathways, thereby determining the constraints on gene optimization for these species. Further in-depth analysis is required to test if it is true for other organisms as well. The Gene Space framework offers a novel and powerful approach for genome analysis at the most basic levels, with promising applications in comparative genomics, evolutionary biology, and gene optimization. Full article
(This article belongs to the Special Issue Latest Advances in Comparative Genomics)
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15 pages, 1841 KB  
Article
Specific Instability of HLA-A*03:01 Expression in HEK-293 Cells
by María Area-Navarro, Alba Pastor-Moreno, Erika Scholz, Américo Cerqueira, Adrián Tirado-Herranz, Miguel Marcilla, Francesc Canals, Manel Juan, José Ramón Palacio and Iñaki Alvarez
Int. J. Mol. Sci. 2025, 26(23), 11357; https://doi.org/10.3390/ijms262311357 - 24 Nov 2025
Viewed by 518
Abstract
HEK-293 is a highly transfectable human cell line widely used as a model for protein expression. Since large amounts of cells are often required for the purification of HLA immunopeptidomes, suspension-growing variants, such as HEK-293F, facilitate the generation of sufficient cell quantities. The [...] Read more.
HEK-293 is a highly transfectable human cell line widely used as a model for protein expression. Since large amounts of cells are often required for the purification of HLA immunopeptidomes, suspension-growing variants, such as HEK-293F, facilitate the generation of sufficient cell quantities. The HLA class I-typing of these cells is HLA-A*02:01, -A*03:01, -B*07:02, and -C*07:02. HEK-293T cells have been previously used as a source of HLA peptide ligands derived from SARS-CoV-2 proteins. In this study, we purified and analyzed the HLA-I immunopeptidome of HEK-293 and HEK-293F cells using mass spectrometry. Cell surface expression of specific HLA-I allotypes was determined using flow cytometry with allele-specific antibodies. The HLA-I immunopeptidome of HEK-293 cells contained ligands from all three HLA-I allotypes, whereas that of HEK-293F cells lacked peptides derived from HLA-A*03:01. Flow cytometry experiments confirmed the absence of HLA-A*03:01 expression on the surface of HEK-293F cells. Additionally, we generated a HEK-293 transfectant co-expressing the β5i proteasome subunit and the SARS-CoV-2 Spike protein. This transfectant showed selective loss of HLA-A*03:01 expression, suggesting that HEK-293 linages tend to specifically lose this allotype. We propose that HEK-293F cells are unsuitable for the identification of HLA-A*03:01 ligands or for stimulating T-cell responses restricted to this allele. Moreover, HLA-A*03:01 expression should be regularly monitored in HEK-293-derived cells. Full article
(This article belongs to the Special Issue Latest Advances in Comparative Genomics)
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21 pages, 1541 KB  
Article
Comparative Analysis of Genetic Risk for Viral-Induced Axonal Loss in Genetically Diverse Mice
by Tae Wook Kang, Aracely Perez-Gomez, Koedi Lawley, Colin R. Young, C. Jane Welsh and Candice L. Brinkmeyer-Langford
Int. J. Mol. Sci. 2025, 26(21), 10727; https://doi.org/10.3390/ijms262110727 - 4 Nov 2025
Cited by 1 | Viewed by 629
Abstract
Among mouse models of neurological disease, Theiler’s murine encephalomyelitis virus (TMEV) provides a unique platform by using a naturally occurring viral trigger, paralleling the role of infections like Epstein–Barr virus in multiple sclerosis (MS). Just as not all individuals with predisposing viral infections [...] Read more.
Among mouse models of neurological disease, Theiler’s murine encephalomyelitis virus (TMEV) provides a unique platform by using a naturally occurring viral trigger, paralleling the role of infections like Epstein–Barr virus in multiple sclerosis (MS). Just as not all individuals with predisposing viral infections develop the same neurological disease, not all mouse strains develop the same diseases following TMEV infection, so susceptibility is dictated by genetic background. For example, certain sets of alleles, called haplotypes, of the major histocompatibility complex (MHC) region have been associated with susceptibility to TMEV-induced demyelination (TVID) and MS. However, our previous work revealed that these MHC susceptibility haplotypes are not the sole contributors to TMEV-induced diseases in all mice. We infected mice from the genetically diverse Collaborative Cross (CC), a resource designed to reflect human population-level genetic variation. All 15 CC strains tested exhibited some form of neurological phenotype or CNS lesion following TMEV infection. However, chronic radiculoneuropathy characterized by axonal degeneration with myelin loss was observed in the CNS of only two strains, CC002 and CC023, which had markedly different immune responses and clinical profiles throughout the course of infection. Moreover, the pathology seen in CC002 and CC023 was not the same as what is typically seen in TVID. We used previous results from RNA sequencing of the hippocampus and spinal cord to test our hypothesis that myelin loss in these strains resulted from the convergent biological effects of multiple genetic risk variants, many previously unassociated with TMEV-induced diseases. These findings identify novel genetic targets and demonstrate the utility of genetically diverse models for uncovering complex neuroimmune interactions. Full article
(This article belongs to the Special Issue Latest Advances in Comparative Genomics)
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21 pages, 3173 KB  
Article
Association of the TGFB1 Gene Polymorphisms with Pain Symptoms and the Effectiveness of Platelet-Rich Plasma in the Treatment of Lateral Elbow Tendinopathy: A Prospective Cohort Study
by Alicja Jarosz, Justyna Wrona, Anna Balcerzyk-Matić, Karol Szyluk, Tomasz Nowak, Tomasz Iwanicki, Joanna Iwanicka, Marcin Kalita, Wojciech Kania, Katarzyna Gawron and Paweł Niemiec
Int. J. Mol. Sci. 2025, 26(6), 2431; https://doi.org/10.3390/ijms26062431 - 8 Mar 2025
Cited by 2 | Viewed by 1642
Abstract
The regenerative properties of platelet-rich plasma (PRP) result from the high concentration of growth factors, including transforming growth factor beta 1 (TGF-β1). Nevertheless, this form of therapy may not always be effective due to the variability in genetic factors. In this study, the [...] Read more.
The regenerative properties of platelet-rich plasma (PRP) result from the high concentration of growth factors, including transforming growth factor beta 1 (TGF-β1). Nevertheless, this form of therapy may not always be effective due to the variability in genetic factors. In this study, the association of TGFB1 gene polymorphisms with the effectiveness of lateral elbow tendinopathy (LET) treatment with PRP was investigated. The effectiveness of therapy was assessed using minimal clinically important difference (MCID) and patient-reported outcome measures (PROM), specifically visual analog scale (VAS), quick version of disabilities of the arm, shoulder, and hand score (QDASH), and patient-rated tennis elbow evaluation (PRTEE) for two years (in weeks 2, 4, 8, 12, 24, 52, and 104). The most effective therapy was noticed in CC rs2278422 genotype carriers, whereas carriers of AA, CC, and CC genotypes (rs12461895, rs4803455, rs2241717) showed more severe pain before therapy. Moreover, the analyses revealed an association of studied polymorphisms with such parameters of blood morphology as eosinophils (EOS), neutrophils (NEU), and monocytes (MONO). In conclusion, genotyping of rs2278422 variant may be a valuable diagnostic method for patient selection for PRP therapy, while genotyping of rs12461895, rs4803455, and rs2241717 polymorphisms may be used for prediction of increased risk of pain sensation. Full article
(This article belongs to the Special Issue Latest Advances in Comparative Genomics)
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