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Research: Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection
- Jian-Hai Chen,
- Patrick Landback,
- Deanna Arsala,
- Alexander Guzzetta,
- Shengqian Xia,
- Jared Atlas,
- Dylan Sosa,
- Yong E. Zhang,
- Jingqiu Cheng,
- Bairong Shen,
- and Manyuan Long
Genome Res. March 2025 35: 379-392; Published in Advance February 14, 2025, doi:10.1101/gr.279498.124
...innovations during primate or human evolution, including the nervous system, head and neck, eyes, and the musculoskeletal system. The enrichment of these disease systems points to the driving forces of both sexual selection and adaptive evolution for young genes, which tend to display specialized functions...
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Method: Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution
- Paul Ashford,
- Alexander M. Frankell,
- Zofia Piszka,
- Camilla S.M. Pang,
- Mahnaz Abbasian,
- Maise Al Bakir,
- Mariam Jamal-Hanjani,
- Nicholas McGranahan,
- Charles Swanton,
- and Christine A. Orengo
Genome Res. March 2026 36: 561-577; Published in Advance February 19, 2026, doi:10.1101/gr.278663.123
...adenocarcinomas, including some metabolic enzymes with the potential to be neofunctional. The postduplication diversification of driver genes and functions may indicate selection for somatic copy number changes in lung tumors and an increased scope for tumor adaptations.Cancers result from the evolutionary...
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Method: EnDeep4mC predicts DNA N⁴-methylcytosine sites using a dual-adaptive feature encoding framework in deep ensembles
- Shuyu Zhang,
- Quan Zou,
- Mengting Niu,
- Zhibin Lv,
- Antony Stalin,
- and Ximei Luo
Genome Res. March 2026 36: 589-599; Published in Advance February 17, 2026, doi:10.1101/gr.280977.125
...stages of feature-model cross-evaluation and dynamic feature fusion. The core innovation of the framework is to establish a 3D selection space of species-model-features and to realize the dynamic adaptation of feature combinations through a two-layer optimization mechanism.The first stage is feature...
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Method: Label-free selection of marker genes in single-cell and spatial transcriptomics with geneCover
- An Wang,
- Stephanie Hicks,
- Donald Geman,
- and Laurent Younes
Genome Res. December 2025 35: 2744-2755; Published in Advance November 12, 2025, doi:10.1101/gr.280539.125
...to small cell populations. This is because the data structure these methods seek to recover is predominantly influenced by genes with high variability, or, as in the case of DUBStepR, the selection process itself is driven by explained variance. Consequently, these imputation-based approaches may overlook...
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Method: Genotyping of selected germline adaptive immune system loci using short-read sequencing data
- Michael K.B. Ford,
- Ananth Hari,
- Meredith Yeager,
- Lisa Mirabello,
- Stephen Chanock,
- Ibrahim Numanagić,
- COVNET Consortium,
- and S. Cenk Sahinalp
Genome Res. September 2025 35: 2076-2086; Published in Advance August 5, 2025, doi:10.1101/gr.280314.124
...approaches. In particular, germline adaptive immune system genes, like immunoglobulin (IG) and T cell receptor (TR) genes, are particularly hard to genotype using classic reference-based methods owing to their highly repetitive and homologous nature. In this paper, we present ImmunoTyper2, a new...
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Research: Independent expansion, selection, and hypervariability of the TBC1D3 gene family in humans
- Xavi Guitart,
- David Porubsky,
- DongAhn Yoo,
- Max L. Dougherty,
- Philip C. Dishuck,
- Katherine M. Munson,
- Alexandra P. Lewis,
- Kendra Hoekzema,
- Jordan Knuth,
- Stephen Chang,
- Tomi Pastinen,
- and Evan E. Eichler
Genome Res. November 2024 34: 1798-1810; Published in Advance August 6, 2024, doi:10.1101/gr.279299.124
...to a subset of copies and, most notably, from a single paralog group: TBC1D3-CDKL. These observations may help explain why a gene potentially important in cortical development can be so variable in the human population.Gene duplication followed by adaptation is one of the primary forces by which new genes...
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Method: Parallel analysis of replication timing, gene expression, and copy number with PARTAGE
- Lakshana Sruthi Sadu Murari,
- Quinn Dickinson,
- Silvia Meyer-Nava,
- and Juan Carlos Rivera-Mulia
Genome Res. March 19, 2026 ; Published in Advance March 19, 2026, doi:10.1101/gr.281532.125
...limitation is the lack of methods enabling the simultaneous measurement of RT and gene expression from the same samples. Althoughmultiple RT profilingmethods exist at the ensemble population level (Marchal et al. 2018; Hulke et al. 2020; Rivera-Mulia et al. 2022; Wheeler et al. 2025), as well...
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Method: Robust and efficient annotation of cell states through gene signature scoring
- Laure Ciernik,
- Agnieszka Kraft,
- Florian Barkmann,
- Josephine Yates,
- and Valentina Boeva
Genome Res. March 2026 36: 630-644; Published in Advance February 18, 2026, doi:10.1101/gr.280926.125
.... In contrast, ANS-based annotation reached optimal accuracy when excluding only the 50 most highly expressed genes and maintained high accuracy even without gene filtering, directly demonstrating the benefits of the adaptive control gene selection. Together, these results confirm that our proposed control gene...
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Method: Analysis of coding gene expression from small RNA sequencing
- Aygun Azadova,
- Anthonia Ekperuoh,
- Greg N. Brooke,
- and Antonio Marco
Genome Res. March 2026 36: 611-618; Published in Advance February 10, 2026, doi:10.1101/gr.281364.125
...of microRNA expression analyses is reflected by the existence of thousands of sRNA-seq studies in which matched total RNA-seq data are often unavailable. The lack of paired sequencing experiments limits the analysis of microRNA–gene regulatory networks. Here, we explore whether protein-coding gene...
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Resource: Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease
- Kangli Wang,
- Weikun Xia,
- Yingli Gu,
- Songpeng Zu,
- Qian Yang,
- Maria Luisa Amaral,
- Yaozhi Wang,
- Allen Wang,
- Xiang-Dong Fu,
- William C. Mobley,
- and Bing Ren
Genome Res. March 4, 2026 ; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...-9051/26; www..org Genome Research 1 www..org but also in the connections between genes and chromatin regions in glia populations during aging and PD (Adams et al. 2024). However, human samples often suffer from inherent genetic variability, limited age representation, and low neuron capture rates, complicating...
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