Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations. This Review discusses advances in understanding its immunopathogenesis, the evolution of targeted therapeutic strategies, and emerging approaches to restore immune tolerance. Challenges and opportunities in achieving durable remission or cure in SLE are also explored.
“Historically, this has been a very challenging problem. People don’t know where to start,” said senior author Megan Dennis, associate director of genomics at the UC Davis Genome Center and associate professor in the Department of Biochemistry and Molecular Medicine and MIND Institute at the University of California, Davis.
In 2022, Dennis was a co-author on a paper describing the first sequence of a complete human genome, known as the ‘telomere to telomere’ reference genome. This reference genome includes the difficult regions that had been left out of the first draft published in 2001 and is now being used to make new discoveries.
Dennis and colleagues used the telomere-to-telomere human genome to identify duplicated genes. Then, they sorted those for genes that are: expressed in the brain; found in all humans, based on sequences from the 1,000 Genomes Project; and conserved, meaning that they did not show much variation among individuals.
They came out with about 250 candidate gene families. Of these, they picked some for further study in an animal model, the zebrafish. By both deleting genes and introducing human-duplicated genes into zebrafish, they showed that at least two of these genes might contribute to features of the human brain: one called GPR89B led to slightly bigger brain size, and another, FRMPD2B, led to altered synapse signaling.
“It’s pretty cool to think that you can use fish to test a human brain trait,” Dennis said.
The dataset in the Cell paper is intended to be a resource for the scientific community, Dennis said. It should make it easier to screen duplicated regions for mutations, for example related to language deficits or autism, that have been missed in previous genome-wide screening.
“It opens up new areas,” Dennis said.
Extrachromosomal DNA in cancer.
This review discusses open questions on the evolutionary role of extrachromosomal DNA (ecDNA) in tumor development, including tumorigenesis and metastatic seeding.
The author discuss the mutational landscape on ecDNA, the dynamic ecDNA genotype– phenotype map, the structural evolution of ecDNA, and how knowledge of tissue-specific ecDNA evolutionary paths can be leveraged to deliver more effective clinical treatment.
They also describe how evolutionary theoretical modeling will be instrumental in advancing new research in the field, and we explore how modeling has contributed to our understanding of the evolutionary principles governing ecDNA dynamics.
https://www.cell.com/trends/cancer/fulltext/S2405-8033(25)00146-3 https://sciencemission.com/Extrachromosomal-DNA
Cancers are complex, diverse, and elusive, with extrachromosomal DNA (ecDNA) recently emerging as a crucial player in driving the evolution of about 20% of all tumors. In this review we discuss open questions concerning the evolutionary role of ecDNA in tumor development, including tumorigenesis and metastatic seeding, the mutational landscape on ecDNA, the dynamic ecDNA genotype–phenotype map, the structural evolution of ecDNA, and how knowledge of tissue-specific ecDNA evolutionary paths can be leveraged to deliver more effective clinical treatment. Looking forward, evolutionary theoretical modeling will be instrumental in advancing new research in the field, and we explore how modeling has contributed to our understanding of the evolutionary principles governing ecDNA dynamics.
Humans are often said to be the only primates with “whites of the eyes,” evolved for social communication. But a new study challenges that idea, arguing that the theory lacks evidence and oversimplifies the diversity of primate eye pigmentation.
What makes the human brain distinctive? A new study published in Cell identifies two genes linked to human brain features and provides a road map to discover many more. The research could lead to insights into the functioning and evolution of the human brain, as well as the roots of language disorders and autism.
Not all genes respond in the same way to regulation by the same molecule—a property that might enable cells to produce complex genetic responses.
Genes in living cells may become active or may be suppressed in response to environmental stimuli such as heat or the availability of nutrients. For bacteria, this gene regulation often appears to be a simple “on-off switch” controlled by regulatory proteins called transcription factors (TFs). But researchers have now found that different genes might respond differently to the same stimulus even if they are regulated by the same TF [1]. The team activated genes involved in DNA repair and observed gene-to-gene variations in their protein production patterns. Such differences might have been exploited by evolution to achieve complex responses with relatively few molecular components, the researchers suggest.
In the typical scenario, a TF binds to a region of a so-called promoter, a DNA sequence next to a gene. If the TF is the type that blocks gene expression, it prevents the enzyme RNA polymerase from binding and thus from beginning the process of producing the protein that the gene encodes. Because of thermal fluctuations (noise), the TF may spontaneously unbind, allowing gene expression to proceed until it rebinds. The rate of TF binding depends on its concentration, so fluctuations in concentration will cause changes in gene expression.
At some point during the evolution of life on Earth, inorganic matter became organic, nonliving matter became living. How this happened is one of humankind’s greatest mysteries. Today, scientists work to develop synthetic cells that mimic living cells, hoping to uncover clues that will help answer the question: how did life on Earth begin?
