by Roberto
How do bacteria come up with new genes? I intentionally did not use the phrase "acquire new genes" because, as most STC readers might know, horizontal gene transfer is likely the most frequent way new genes end up in a bacterium's genome. What I ask now is different. After more than four billion years of evolution, are bacteria still giving birth to genes de novo? In a prior post, Christoph addressed this concept of making genes "from scratch," when he described ORFan genes. ORFan genes are defined as having no homologs outside a given lineage and thus are candidates for being present in a particular genome because they were born there. But ORFans, as their name implies, already contain an open reading frame, they already are genes.
Fig. 1. Ways in which a noncoding region can transition into a proto-gene. Source
Can completely non-genic sequences (non-coding and not transcribed) become genes? If so, can we watch the process in "real time"? These are the questions addressed in a recent paper by uz-Zaman and colleagues. The process of going from non-genic DNA to a newly born protein-coding gene must, by necessity, go through an intermediate "proto-gene," where the DNA is transcribed, a new ORF is generated, and eventually can be translated. If the translation product then gains a function, that constitutes de novo gene birth. In the current paper, the authors analyzed isolates from the E. coli Long Term Evolution Experiment (LTEE) from the 50,000-generation time point. They compared the transcriptional and translational patterns of evolved isolates to those of the ancestral strain. Starting from thousands of candidates they were able to whittle down the number to nine proto-genes whose transcription was never observed prior to the LTEE experiment. More than half of the newly transcribed proto-genes (5 of the 9) were the result of an insertion sequence (IS150) transposing nearby. A promoter within the IS150 that transcribes outwardly accounts for the transcription of the proto-gene. The authors refer to this mechanism of proto-gene generation as "promoter recruitment." The other four proto-genes? Two were the result of point mutations and one was a small deletion; these three generated new promoters. Their ninth proto-gene resulted from deletion of some 8,000 base-pairs that brought the non-coding region close to a pre-existing promoter. This last proto-gene appears to have within it a translated ORF. It's thus a "full-grown" proto-gene, ready and waiting to become a functional gene. Quite interestingly, once these proto-genes emerged some increased in frequency and some even reached fixation (present in 100% of the population). Does this mean these proto-genes can provide a fitness benefit? Maybe, maybe not. Perhaps these proto-genes are byproducts of mutations that are beneficial due to effects on pre-existing genes located nearby. Regardless, it's clear E. coli can convert non-genic sequence into proto-genes. But, when it is all said and done, if I was a bacterium looking for new genes... I'd reach out and get them horizontally before I'd go through the trouble of making them from scratch.
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