The thermostability and specificity of ancient proteins.
Were ancient proteins systematically different than modern proteins? The answer to this question is profoundly important, shaping how we understand the origins of protein biochemical, biophysical, and functional properties. Ancestral sequence reconstruction (ASR), a phylogenetic approach to infer the sequences of ancestral proteins, may reveal such trends. We discuss two proposed trends: a transition from higher to lower thermostability and a tendency for proteins to acquire higher specificity over time. We review the evidence for elevated ancestral thermostability and discuss its possible origins in a changing environmental temperature and/or reconstruction bias. We also conclude that there is, as yet, insufficient data to support a trend from promiscuity to specificity. Finally, we propose future work to understand these proposed evolutionary trends.
Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR, United States; Institute of Molecular Biology, University of Oregon, Eugene, OR, United States.
Lucas C
LC
Wheeler
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States; Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, United States.
Shion A
SA
Lim
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States; Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, United States. Electronic address: marqusee@berkeley.edu.
Susan
S
Marqusee
Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR, United States; Institute of Molecular Biology, University of Oregon, Eugene, OR, United States. Electronic address: harms@uoregon.edu.
Michael J
MJ
Harms
D000818:Animals; D019143:Evolution, Molecular; D010802:Phylogeny; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013696:Temperature
D011506:Proteins