---
res:
  bibo_abstract:
  - 'Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that
    bind transcription factor (TF) proteins to up- or down-regulate target genes.
    Decades-long efforts yielded TF-DNA interaction models that predict how strongly
    an individual TF binds arbitrary DNA sequences and how individual binding events
    on the CRE combine to affect gene expression. These insights can be synthesized
    into a global, biophysically realistic, and quantitative genotype-phenotype (GP)
    map for gene regulation, a ‘holy grail’ for the application of evolutionary theory.
    A global map provides a rare opportunity to simulate the long-term evolution of
    regulatory sequences and pose several fundamental questions: How long does it
    take to evolve CREs de novo? How many non-trivial regulatory functions exist in
    sequence space? How connected are they? For which regulatory architecture is CRE
    evolution most rapid and evolvable? In this article, the second of a two-part
    series, we review the application of evolutionary concepts — epistasis, robustness,
    evolvability, tunability, plasticity, and bet-hedging — to the evolution of gene
    regulatory sequences. We then evaluate the potential for a unifying theory for
    the evolution of regulatory sequences and identify key open challenges.@eng'
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Elia
      foaf_name: Mascolo, Elia
      foaf_surname: Mascolo
      foaf_workInfoHomepage: http://www.librecat.org/personId=776a6ed0-a053-11f0-8635-80b95e0e0d53
    orcid: 0000-0003-2977-7844
  - foaf_Person:
      foaf_givenName: Reka E
      foaf_name: Körei, Reka E
      foaf_surname: Körei
      foaf_workInfoHomepage: http://www.librecat.org/personId=50FDE43E-AA30-11E9-A72B-8A12E6697425
  - foaf_Person:
      foaf_givenName: Noa O.
      foaf_name: Borst, Noa O.
      foaf_surname: Borst
  - foaf_Person:
      foaf_givenName: Nicholas H
      foaf_name: Barton, Nicholas H
      foaf_surname: Barton
      foaf_workInfoHomepage: http://www.librecat.org/personId=4880FE40-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0002-8548-5240
  - foaf_Person:
      foaf_givenName: Justin
      foaf_name: Crocker, Justin
      foaf_surname: Crocker
  - foaf_Person:
      foaf_givenName: Gašper
      foaf_name: Tkačik, Gašper
      foaf_surname: Tkačik
      foaf_workInfoHomepage: http://www.librecat.org/personId=3D494DCA-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0002-6699-1455
  bibo_doi: 10.1016/j.gde.2026.102472
  bibo_volume: 98
  dct_date: 2026^xs_gYear
  dct_isPartOf:
  - http://id.crossref.org/issn/0959-437X
  - http://id.crossref.org/issn/1879-0380
  dct_language: eng
  dct_publisher: Elsevier@
  dct_title: 'Long-term evolution of regulatory DNA sequences. Part 2: Theory and
    future challenges@'
...