| 1. |
- Christmas, Matthew, et al.
(författare)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Tidskriftsartikel (refereegranskat)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 2. |
- Kaplow, Irene M., et al.
(författare)
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Relating enhancer genetic variation across mammals to complex phenotypes using machine learning
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Tidskriftsartikel (refereegranskat)abstract
- Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations between enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent and functionally conserved despite low sequence conservation. We developed the Tissue-Aware Conservation Inference Toolkit (TACIT) to associate candidate enhancers with species' phenotypes using predictions from machine learning models trained on specific tissues. Applying TACIT to associate motor cortex and parvalbumin-positive interneuron enhancers with neurological phenotypes revealed dozens of enhancer-phenotype associations, including brain size-associated enhancers that interact with genes implicated in microcephaly or macrocephaly. TACIT provides a foundation for identifying enhancers associated with the evolution of any convergently evolved phenotype in any large group of species with aligned genomes.
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| 3. |
- Schäffer, Tilman E, et al.
(författare)
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Does abalone nacre form by heteroepitaxial nucleation or by growth through mineral bridges?
- 1997
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 9:8, s. 1731-1740
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Tidskriftsartikel (refereegranskat)abstract
- We present experimental support for a model of abalone nacre growth that is based on mineral bridges between successive aragonite tablets rather than on heteroepitaxial nucleation. Interlamellar sheets of organic polymers delineate the aragonite tablets but allow the tablets to grow mineral bridges through pores in the sheets. Atomic force microscope images of interlamellar organic sheets from flat pearls made by Haliotis rufescens (red abalone; marine gastropod mollusk) reveal a fibrous core and holes of 5-50 nm in diameter. Scanning ion conductance microscopy shows that these holes are actually pores through the interlamellar sheets. With the help of statistical analysis we can associate the pore-to-pore spacings in the interlamellar sheets with the observed offsets of successive nacre tablets. These results, supplemented by AFM, SEM, and TEM images, support and extend the model of biofabrication of gastropod nacre which is based on mineral bridges between the aragonite tablets.
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