Current Status of the Molecular Clock Hypothesis

The field of molecular evolution started with the alignment of a few protein sequences in the early 1960s. Among the first results found, the genetic equidistance result has turned out to be the most unexpected. It directly inspired the ad hoc universal molecular clock hypothesis that in turn inspired the neutral theory. Unfortunately, however, what is only a maximum distance phenomenon was mistakenly transformed into a mutation rate phenomenon and became known as such. Previous work studied a small set of selected proteins. We have performed proteome wide studies of 7 different sets of proteomes involving a total of 15 species. All 7 sets showed that within each set of 3 species the least complex species is approximately equidistant in average proteome wide identity to the two more complex ones. Thus, the genetic equidistance result is a universal phenomenon of maximum distance. There is a reality of constant albeit stepwise or discontinuous increase in complexity during evolution, the rate of which is what the original molecular clock hypothesis is really about. These results provide additional lines of evidence for the recently proposed maximum genetic diversity (MGD) hypothesis.

Testing the Molecular Clock Hypothesis

Data Analysis in Molecular Biology and Evolution ◽

10.1007/0-306-46893-x_20 ◽

2005 ◽

pp. 225-231

Keyword(s):

Molecular Clock ◽

Molecular Clock Hypothesis ◽

Clock Hypothesis

An evaluation of the molecular clock hypothesis using mammalian DNA sequences

Journal of Molecular Evolution ◽

10.1007/bf02603118 ◽

1987 ◽

Vol 25 (4) ◽

pp. 330-342 ◽

Cited By ~ 192

Author(s):

Wen-Hsiung Li ◽

Masako Tanimura ◽

Paul M. Sharp

Keyword(s):

Molecular Clock ◽

Dna Sequences ◽

Molecular Clock Hypothesis ◽

Clock Hypothesis

Histone deletion mutants challenge the molecular clock hypothesis

Trends in Biochemical Sciences ◽

10.1016/0968-0004(90)90231-y ◽

1990 ◽

Vol 15 (10) ◽

pp. 374-376 ◽

Cited By ~ 4

Author(s):

Michael J. Behe

Keyword(s):

Molecular Clock ◽

Deletion Mutants ◽

Molecular Clock Hypothesis ◽

Clock Hypothesis

Synonymous Rates at the RpII215 Gene of Drosophila: Variation Among Species and Across the Coding Region

Genetics ◽

10.1093/genetics/152.1.269 ◽

1999 ◽

Vol 152 (1) ◽

pp. 269-280 ◽

Cited By ~ 2

Author(s):

Ana Llopart ◽

Montserrat Aguadé

Keyword(s):

Rna Polymerase Ii ◽

Molecular Clock ◽

Constitutive Expression ◽

Synonymous Substitution ◽

Coding Region ◽

Substitution Rates ◽

Synonymous Mutations ◽

Molecular Clock Hypothesis ◽

Synonymous Substitution Rates ◽

Clock Hypothesis

Abstract The region encompassing the RpII215 gene that encodes the largest component of the RNA polymerase II complex (1889 amino acids) has been sequenced in Drosophila subobscura, D. madeirensis, D. guanche, and D. pseudoobscura. Nonsynonymous divergence estimates (Ka) indicate that this gene has a very low rate of amino acid replacements. Given its low Ka and constitutive expression, synonymous substitution rates are, however, unexpectedly high. Sequence comparisons have allowed the molecular clock hypothesis to be tested. D. guanche is an insular species and it is therefore expected to have a reduced effective size relative to D. subobscura. The significantly higher rate of synonymous substitutions detected in the D. guanche lineage could be explained if synonymous mutations behave as nearly neutral. Significant departure from the molecular clock hypothesis for synonymous and nonsynonymous substitutions was detected when comparing the D. subobscura, D. pseudoobscura, and D. melanogaster lineages. Codon bias and synonymous divergence between D. subobscura and D. melanogaster were negatively correlated across the RpII215 coding region, which indicates that selection coefficients for synonymous mutations vary across the gene. The C-terminal domain (CTD) of the RpII215 protein is structurally and functionally differentiated from the rest of the protein. Synonymous substitution rates were significantly different in both regions, which strongly indicates that synonymous mutations in the CTD and in the non-CTD regions are under detectably different selection coefficients.