Thermos aquaticus
Well-Known Member
Before we can delve too far into the debate about how much of the human genome is functional we first have to define what we mean by functional. The first question we have to ask is if there is a difference between doing something and being functional.
For example, your heart does many things. Your heart makes sounds, it adds 300 g to your body weight, it keeps your pericardium from collapsing, it causes your left lung to be smaller, and it moves blood through your body. Would you say that all of those properties are functions of the heart? If your heart were not pumping blood through your body but it was still adding 300 g to your body weight, would it be correct to say that your heart was still functioning?
The answer to the last question will say a lot about what portion of the human genome has function. If DNA just does something, is that enough to say that it is functional?
The ENCODE consortium famously concluded that around 80% of the human genome has function, but what did they mean by functional? As it turned out, their definition of DNA being functional was equivalent to your heart having function because it adds 300 g to your body weight. The ENCODE consortium considered DNA functional if it was transcribed, bound transcription factors, bound histones, or was methylated along with some other less important factors. The problem is that these are just examples of DNA doing something. Junk also does stuff, but that doesn't make it functional in the same way moving blood makes a heart functional.
The real problem for the ENCODE consortium is only 10% or so of the genome is conserved. In other words, 90% of the human genome is accumulating mutations at a rate consistent with neutral drift. If there really is important function in 80% of the human genome, then how is it that 70% of that function doesn't change no matter how many mutations we add to it? That makes no sense.
If we look beyond humans we find that the size of genomes in closely related species can differ by several fold. More distantly related species also provide insight. The bladderwort genome is just 0.083 billion bases with genes taking up more than 95% of the total genome. The human is 3 billion bases with about the same number of genes as the bladderwort genome, yet both function just fine. The bladderwort genome has had all of its junk DNA removed, and it does just fine. The onion genome has 16 billion bases, 5 times that of the human genome, yet it is no more complex than humans. The pufferfish genome is just 0.4 billion bases, about a 7th of the human genome, yet they aren't any less complex than a human and have about the same number of genes. What gives?
The only conclusion that makes sense is that the vast majority, about 90%, of the human genome does not have a vital function that affects human fitness. 80% of the human genome may do something, but that doesn't mean it makes a difference to human fitness which is the definition of function that most people use.
For example, your heart does many things. Your heart makes sounds, it adds 300 g to your body weight, it keeps your pericardium from collapsing, it causes your left lung to be smaller, and it moves blood through your body. Would you say that all of those properties are functions of the heart? If your heart were not pumping blood through your body but it was still adding 300 g to your body weight, would it be correct to say that your heart was still functioning?
The answer to the last question will say a lot about what portion of the human genome has function. If DNA just does something, is that enough to say that it is functional?
The ENCODE consortium famously concluded that around 80% of the human genome has function, but what did they mean by functional? As it turned out, their definition of DNA being functional was equivalent to your heart having function because it adds 300 g to your body weight. The ENCODE consortium considered DNA functional if it was transcribed, bound transcription factors, bound histones, or was methylated along with some other less important factors. The problem is that these are just examples of DNA doing something. Junk also does stuff, but that doesn't make it functional in the same way moving blood makes a heart functional.
The real problem for the ENCODE consortium is only 10% or so of the genome is conserved. In other words, 90% of the human genome is accumulating mutations at a rate consistent with neutral drift. If there really is important function in 80% of the human genome, then how is it that 70% of that function doesn't change no matter how many mutations we add to it? That makes no sense.
If we look beyond humans we find that the size of genomes in closely related species can differ by several fold. More distantly related species also provide insight. The bladderwort genome is just 0.083 billion bases with genes taking up more than 95% of the total genome. The human is 3 billion bases with about the same number of genes as the bladderwort genome, yet both function just fine. The bladderwort genome has had all of its junk DNA removed, and it does just fine. The onion genome has 16 billion bases, 5 times that of the human genome, yet it is no more complex than humans. The pufferfish genome is just 0.4 billion bases, about a 7th of the human genome, yet they aren't any less complex than a human and have about the same number of genes. What gives?
The only conclusion that makes sense is that the vast majority, about 90%, of the human genome does not have a vital function that affects human fitness. 80% of the human genome may do something, but that doesn't mean it makes a difference to human fitness which is the definition of function that most people use.