Quantifying the Influence of Genetic Context on Duplicated Mammalian Genes.

Gene duplication is a fundamental part of evolutionary innovation. While paralogs frequently exhibit asymmetric evolutionary rates, the extent to which genetic context influences asymmetric evolution remains unclear. In this study, we investigate the role of genetic context in shaping evolutionary divergence within both single-gene and multigene duplications, leveraging microsynteny to differentiate source and target copies. Using a dataset of 193 mammalian genome assemblies and a bird outgroup, we systematically analyze patterns of sequence divergence between paralogs. We find that most paralogs have no detectable difference in their evolutionary rates. When there is rate asymmetry, target copies, those relocated to new genomic locations, exhibit elevated evolutionary rates compared to source copies in ancestral locations. This asymmetry is influenced by the genomic distance between copies, the size of the duplicated region, and the position within multigene duplications. We also demonstrate that the "choice" of the fast-evolving copy in multigene duplications occurs in a collective, block-wise manner more often than expected by random chance. Our findings highlight the importance of genetic context in modulating postduplication divergence, where differences in cis-regulatory elements and co-expressed gene clusters between source and target copies may be responsible. This study presents a large-scale study of asymmetric evolution in duplications of varying size, offering new insight into how genome architecture shapes functional diversification of paralogs.