Significance A long-standing mystery in evolutionary genomics concerns the lineage-specific expansions of genome size in eukaryotes relative to prokaryotes. One argument is that the cellular complexity and elevated gene numbers in eukaryotes were impossible without a mitochondrion. However, the energetic burden of a gene is typically no greater, and generally becomes progressively smaller, in larger cells in both bacteria and eukaryotes, and this is true for costs measured at the DNA, RNA, and protein levels. These results eliminate the need to invoke an energetics barrier to genome complexity.
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