Comparison between genomic alterations in mouse, pig, and human through whole-genome sequencing

Abstract

Somatic mutations gradually accumulate as an organism develops and grows. These somatic mutations are not only associated with disease but also serve as important indicators: at the cellular level, they reveal the internal and external effects cells have undergone; at the organism level, they can reveal species-specific patterns. In this study, we conducted whole-genome sequencing on single-cell clonal expansion samples from various tissues of mice, pigs, and human cadavers. A total of 69 samples were analyzed, including muscle, skin, kidney, and other tissues. We compared the number of single nucleotide variants and structural variants across species and tissues, observing differences in the distribution and characteristics of these mutations between humans, mice, and pigs. Additionally, we performed mutational signature analysis to explore the genomic landscapes of these organisms. UV radiation-related mutational signatures were identified in human skin but not in muscle or other animal samples. Furthermore, two mutational signatures, catalogue of somatic mutations in cancer (COSMIC) single base substitution 5 and 40, were mostly present in mice and pigs, although their relative contributions differed. Through these results, we present several hypotheses for estimating species and tissue similarity using Ti/Tv (transition/transversion) ratio, diversity in the number of mutations in the same tissue origin, and the number of single-nucleotide variants is not proportional to that of structural variations. These comparative analyses of genomic alterations across species enhance our understanding of the mechanisms driving somatic mutation accumulation, offering valuable insights into the shared patterns of genomic alterations across species and their implication for animal disease models.