Emergence and influence of sequence bias in evolutionarily malleable, mammalian tandem arrays

BMC Biology

Research Article

E. Josephine Clowney¹  Margarita V. Brovkina²  Matthew L. Holding³  Margaret A. Chapman⁴ 

[1] Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA;Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA;Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA;Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA;Neurosciences Graduate Program, University of Michigan Medical School, Ann Arbor, MI, USA;

关键词: Chemosensation;    Barriers;    Xenobiotic metabolism;    Genome organization;    Isochores;    Sequence bias;    CpG island;    Heterochromatin;    Olfaction;    Immune system;   

DOI  :  10.1186/s12915-023-01673-4

 received in 2023-04-25, accepted in 2023-08-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe radiation of mammals at the extinction of the dinosaurs produced a plethora of new forms—as diverse as bats, dolphins, and elephants—in only 10–20 million years. Behind the scenes, adaptation to new niches is accompanied by extensive innovation in large families of genes that allow animals to contact the environment, including chemosensors, xenobiotic enzymes, and immune and barrier proteins. Genes in these “outward-looking” families are allelically diverse among humans and exhibit tissue-specific and sometimes stochastic expression.ResultsHere, we show that these tandem arrays of outward-looking genes occupy AT-biased isochores and comprise the “tissue-specific” gene class that lack CpG islands in their promoters. Models of mammalian genome evolution have not incorporated the sharply different functions and transcriptional patterns of genes in AT- versus GC-biased regions. To examine the relationship between gene family expansion, sequence content, and allelic diversity, we use population genetic data and comparative analysis. First, we find that AT bias can emerge during evolutionary expansion of gene families in cis. Second, human genes in AT-biased isochores or with GC-poor promoters experience relatively low rates of de novo point mutation today but are enriched for non-synonymous variants. Finally, we find that isochores containing gene clusters exhibit low rates of recombination.ConclusionsOur analyses suggest that tolerance of non-synonymous variation and low recombination are two forces that have produced the depletion of GC bases in outward-facing gene arrays. In turn, high AT content exerts a profound effect on their chromatin organization and transcriptional regulation.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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