Abstract
Gene duplication is a major driver of genomic innovation, but whether paralog accumulation scales uniformly with increasing genome size across the domain Archaea remains unclear. This study presents a domain-wide analysis of 1,829 archaeal genomes and their predicted proteomes to evaluate protein family expansions, their distribution, and lineage-specific patterns of gene duplication. Protein family expansions were classified as recent (90% sequence identity), intermediate (70%), or old (40%) duplications based on sequence-identity thresholds within each family. The findings show that gene duplication content is decoupled from overall proteome size at high sequence-identity levels, indicating that recent paralog retention does not correlate with proteome expansion. Archaeal lineages exhibit contrasting gene duplication profiles. All 1,829 genomes contained paralogs at the 40% sequence identity threshold, indicating the widespread presence of ancient or divergent duplication events. In contrast, paralogs detected at the 90% identity threshold, showed substantial variation across lineages. Their proportion reached up to 16.6% in groups such as Halobacteria, whereas only 74 genomes (4.04%) completely lacked paralogs at this threshold. Highly duplicated families are enriched for membrane transport systems (ABC/MFS), central metabolic enzymes (e.g., acetyl-CoA synthetase), a high proportion of uncharacterized functions, and mobile elements, predominantly transposases. Notably, we identified 314 transposase protein families in Archaea, distributed in 161 unique families in Archaea and 153 families shared with Bacteria, suggesting mechanisms of interdomain gene transfer. Overall, paralog accumulation in Archaea is a lineage-specific phenomenon shaped by targeted functional duplications and mobile element activity, rather than a simple consequence of proteome growth.