Effect versus function.

There has been quite a bit of discussion in the media recently about discoveries of [indirect evidence for] functions in [small portions of] non-coding DNA. Unfortunately, the parts in square brackets are often omitted. It is also the case that many reports overlook the important distinction between effect and function, leaving readers with the impression that non-coding DNA can only be either totally insignificant or vitally important.

Here is the relevant part of the Merriam-Webster Dictionary entry on function:

“The action for which a person or thing is specially fitted, used, or responsible or for which a thing exists.”

And on effect:

“Something that is produced by an agent or cause; something that follows immediately from an antecedent; a resultant condition.”

In other words, a function fulfills a specific role to produce a positive result, with a close fit between cause and outcome shaped by either design (in human technology) or natural selection (in biological systems). Effects are also the outcome of identifiable causes, but they can be positive, neutral, or negative and may be generated directly or indirectly by the causal mechanism. Thus, it is not possible to have a function without any effects, but something can exert an effect — perhaps a very important one — without this constituting a function.

Consider an example. The immune system of the body has a clear function: to defend against pathogens. Viruses likewise have functions, but this only makes sense if one considers the issue from the perspective of the viruses themselves and not of their hosts. Specifically, parts of the virus function in allowing them to circumvent the host’s immunity and to usurp its replication machinery. Viruses do, however, have effects on hosts — usually negative, but apparently sometimes indirectly positive.

The genomes of eukaryotes consist of many types of DNA sequences. The exons that encode proteins make up a small percentage (less than 2% in humans), and the rest is non-coding DNA of various sorts: introns, pseudogenes, satellite DNA, and especially transposable elements (also called TEs, transposons, or mobile elements). The latter represent a diverse set of sequences that are capable of moving about and duplicating in the genome independently of the normal replication process. In this sense, they are often considered “parasites” of the “host” genome. Overall, TEs also make up the largest portion of non-coding DNA in the genomes analyzed so far (at least 45% in humans), although the particular types, abundances, and levels of activity of TEs vary among species.

Some TEs have evidently been co-opted (exapted) to perform functions at the host level, meaning that they have moved from being parasites to integrated participants in the functioning of the genome. This includes regulating genes, involvement in the genetic cutting-and-splicing mechanism of the vertebrate immune system, and perhaps cellular stress response. On the other hand, many diseases can result from mutations caused by the insertion of a TE into an existing gene. From the perspective of the host, TEs can have different effects depending on the context: some TEs are functional but some are detrimental. The large majority, however, have not been shown to fall into either category.

Nevertheless, a lack of evidence for either function or harm does not mean that TEs are without effects. It is well known that the total amount of DNA (genome size) is linked to cell size, cell division rate, metabolic rate, and developmental rate. In other words, a large genome is typically found in large, slowly dividing cells within an organism displaying a low metabolic rate and sluggish development. Conversely, organisms with high metabolic rate or rapid development tend to have small genomes. To the extent that total DNA content directly affects cell size and division, these can be considered effects — by their presence in the aggregate — of non-coding DNA elements.

Is slowing down metabolism or delaying development a function? Some authors think so, but most would argue that these are effects that are tolerated by the organism because they are not overly detrimental. That is, parasites spread within the genome and individually may have little or no effect (and no function), but in sum may have substantial effects on the cell and organism. The amount of accumulation would depend on the tolerance of the organism based on its biology. For example, it is unlikely that a mammal with a high metabolic rate could have a genome the size of a salamander’s.

The point of this discussion is to note that seeking functions for non-coding DNA is an interesting area of research, but that even if most sequences are not functional, they can still be important from a biological perspective. Similarly, one would not invoke function for hosts to explain the existence of viruses, nor would one dismiss viruses as unimportant if functions were never found at the host level. One would, however, focus considerable attention on explaining how viruses spread, why some are more virulent than others, and how they exert their effects.

1 comment to Effect versus function.

  • RPM

    I like this distinction. From my persepctive, the most important effect of repetitive DNA is in initiating rearrangements and duplications. This has been exapted as a function in some cases (ie, adaptive immune system), but rearrangements induced by repeats are mostly due to effects of the repeats rather than a function.


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