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Published on: September 2, 2025
The mysterious orphans of Mycoplasmataceae
Tatiana V Tatarinova1,2, Inna Lysnyansky3, Yuri V Nikolsky4,5,6
1Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, 90027, CA, USA. tatiana.tatarinova@usc.edu.
Background:
The length of a protein sequence is largely determined by its function. In certain species, it may be also affected by additional factors, such as growth temperature or acidity. In 2002, it was shown that in the bacterium Escherichia coli and in the archaeon Archaeoglobus fulgidus, protein sequences with no homologs were, on average, shorter than those with homologs (BMC Evol Biol 2:20, 2002). It is now generally accepted that in bacterial and archaeal genomes the distributions of protein length are different between sequences with and without homologs. In this study, we examine this postulate by conducting a comprehensive analysis of all annotated prokaryotic genomes and by focusing on certain exceptions.
Results:
We compared the distribution of lengths of "having homologs proteins" (HHPs) and "non-having homologs proteins" (orphans or ORFans) in all currently completely sequenced and COG-annotated prokaryotic genomes. As expected, the HHPs and ORFans have strikingly different length distributions in almost all genomes. As previously established, the HHPs, indeed are, on average, longer than the ORFans, and the length distributions for the ORFans have a relatively narrow peak, in contrast to the HHPs, whose lengths spread over a wider range of values. However, about thirty genomes do not obey these rules. Practically all genomes of Mycoplasma and Ureaplasma have atypical ORFans distributions, with the mean lengths of ORFan larger than the mean lengths of HHPs. These genera constitute over 80 % of atypical genomes.
Conclusions:
We confirmed on a ubiquitous set of genomes that the previous observation of HHPs and ORFans have different gene length distributions. We also showed that Mycoplasmataceae genomes have very distinctive distributions of ORFans lengths. We offer several possible biological explanations of this phenomenon, such as an adaptation to Mycoplasmataceae's ecological niche, specifically its "quiet" co-existence with host organisms, resulting in long ABC transporters.
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