Periodic recurrence of methionines: fossil of gene fusion?

Abstract

As we have recently shown, "20% of proteins are made of uniform size units of ;'123 aa for eukaryotes and '152 aa for prokaryotes. Such regularity may reflect certain past events in protein evolution by fusion (molecular recombination) of a spectrum of standard-size protein-coding DNA segments-the early genes. Consequently, methionines, as start residues, would mark those locations in proteins that correspond to the DNA recombination sites-the borders between the fused genes. This positional preference of the methionines may still survive as a fossil of the early protein sequence organization. In this study we address the question how methionines are distributed in modern protein sequences. This analysis of eukaryotic sequences shows that methionine residues do preferentially appear at the positions corresponding to the multiples of the unit size, as predicted.The early notion that proteins might have a standard modular structure (1) has been recently confirmed (2, 3). A welldetectable (=20%) excess of certain protein sequence sizes has been found. The preferred polypeptide chain lengths are multiples of 123 ± 3 aa for eukaryotes and 152 ± 4 aa for prokaryotes (3). Most (if not all) species and most protein types and families contribute to this general trend. The protein sequence size regularity is particularly strong among more conserved proteins (e.g., enzymes) (3). This could be taken as an indication that the observed underlying order in the protein sequence lengths is a reflection of an ancient regular organization of proteins.At some early stages, proteins might evolve by combinatorial fusion (shuffling) of genes initially of the same elementary size. It is proposed that the early genes could have been fused through molecular recombination events-insertions of the protein-coding DNA circles of certain optimal size (3, 4). The size of 300-500 bp both ensures maximal efficiency of the DNA circularization (5) and has appropriate coding capacity (100-170 aa). The recombination events-that is, insertions and deletions of the standard unit-size DNA circles-might have occurred anywhere along the sequences. However, the locations of the sites of recombination preferentially at the ends of already existing protein-coding segments would be perhaps more likely. In this case the new composite genes would carry intact component genes (segments). One consequence of the described hypothetical process of gene fusion would be the more frequent (initially perhaps strictly regular) appearance of the initiation triplets at the borders between the unit-length sequence segments. If the newly acquired methionines (initiation residues) were not in a conflict with the performance of the new recombination protein product, the presence of the methionines at the segment borders would be retained during later stages of protein evolution, and they still might be detectable in modern sequences (4). Similar behavior would be expected from termination triplets as well, or rather from mutational derivatives thereof. However, unlike...

Selection and Methionine Accumulation in the Fat Body Protein 2 Gene (FBP2), a Duplicate of the Drosophila Alcohol Dehydrogenase (ADH) Gene

“…Conserved parts of the putative polypeptide include the NAD + coenzyme-binding site (Rat et al 1991). Kolker and Trifonov (1995) showed that when proteins are produced from an ancient gene fusion, methionines found within the polypeptide may be remnants of former start sites, a mechanism that would apply to 20% of proteins. This hypothesis cannot apply to FBP2, where methionines make up one out of five residues, and frequently occur in tandems of two or three.…”

Elucidating Sequence Codes: Three Codes for Evolution

“…Strong support for the early gene fusion theory came from the observation that methionine residues showed a small but detectable excess about every 120 residues in eukaryotic proteins and 145 residues in prokaryotes. 23 Additional estimates of unit size are provided by the size distribution of DNA mobile elements, 24 by typical separations between curved DNA regions, 25 and by distributions of translation pause sites along mRNA, 26,27 apparently to allow for independent folding of consecutive protein domains. The data together with estimated mean values for the prokaryotic and eukaryotic units are presented in Table 2.…”

Partition of aminoacyl-tRNA synthetases in two different structural classes dating back to early metabolism: Implications for the origin of the genetic code and the nature of protein sequences

“…Since methionines are known to begin coded protein sequences and sulfur chemistry has been invoked in different cases for ligation of peptides, it is intriguing to note that Kolker and Trifonov (1995) demonstrated a periodicity of appearance of methionines in modern prorein sequences equal to the estimated size of ancient genes.…”