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Non-base-contacting residues enable kaleidoscopic evolution of metazoan C2H2 zinc finger DNA binding.

Abstract：

BACKGROUND:The C2H2 zinc finger (C2H2-ZF) is the most numerous protein domain in many metazoans, but is not as frequent or diverse in other eukaryotes. The biochemical and evolutionary mechanisms that underlie the diversity of this DNA-binding domain exclusively in metazoans are, however, mostly unknown. RESULTS:Here, we show that the C2H2-ZF expansion in metazoans is facilitated by contribution of non-base-contacting residues to DNA binding energy, allowing base-contacting specificity residues to mutate without catastrophic loss of DNA binding. In contrast, C2H2-ZF DNA binding in fungi, plants, and other lineages is constrained by reliance on base-contacting residues for DNA-binding functionality. Reconstructions indicate that virtually every DNA triplet was recognized by at least one C2H2-ZF domain in the common progenitor of placental mammals, but that extant C2H2-ZF domains typically bind different sequences from these ancestral domains, with changes facilitated by non-base-contacting residues. CONCLUSIONS:Our results suggest that the evolution of C2H2-ZFs in metazoans was expedited by the interaction of non-base-contacting residues with the DNA backbone. We term this phenomenon "kaleidoscopic evolution," to reflect the diversity of both binding motifs and binding motif transitions and the facilitation of their diversification.

journal_name

Genome Biol

journal_title

Genome biology

authors

Najafabadi HS,Garton M,Weirauch MT,Mnaimneh S,Yang A,Kim PM,Hughes TR

doi

10.1186/s13059-017-1287-y

subject

Has Abstract

pub_date

2017-09-06 00:00:00

pages

167

issue

1

eissn

1474-7596

issn

1474-760X

pii

10.1186/s13059-017-1287-y

journal_volume

18

pub_type

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