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Replicating experimental evolution from ancestral proteins shows that historical contingency steadily overwhelms chance and necessity as the primary cause of evolutionary variation in molecular sequences on long phylogenetic timescales.

In the ancestor of mammals, a multifunctional innate immune protein evolved when a mutation enhanced the protein’s pro-inflammatory activity and proteolytic regulation without disrupting the protein’s antimicrobial activity.

Transgenic animals carrying reconstructed ancestral alleles reveal how two ancient mutations allowed a regulatory protein to evolve a controlling role in embryonic development in flies.

Using different sets of input sequences to evolutionary reconstruction algorithms results in the exploration of many possible models, the intergration over which produces significantly more accurate models.

The convergent evolution of unusually strict substrate specificity in apicomplexan LDHs arose by classic neofunctionalization of a duplicated MDH gene via few mutations of large effect.

Experimentally reconstructing the evolution of the molecular complex that animals use to orient the mitotic spindle establishes a simple genetic and physical mechanism for the emergence of a function essential for multicellularity.

Applying ancestral sequence reconstruction techniques to protein kinases reveals the mutations that underlie different modes of activation.

The human-like joint proportions of Australopithecus afarensis evolved independently, making 'Lucy' and her kind the earliest known evolutionary experiment in obligate bipedalism.

Ancestral sequence reconstruction of an essential muscle protein involved in oxygen storage and transport accurately tracks secondary aquatic transitions in a speciose clade of insectivorous mammals.

In-planta ancestral protein resurrection of the female determinant of self-incompatibility specificity in Arabidopsis halleri demonstrates that two allelic variants currently segregating as distinct receptor-ligand combinations diverged through an asymmetrical process.