Changing the way we look at the world
Genetic differences between humans and chimpanzees
Much has been written about the differences between human and chimpanzee genomes. The published percentage difference ranges from about 2% to up to 15%. It all depends on how the comparison is done.
This blog post focuses on three very specific differences which have come to light in recent years. These are orphan genes, HARs and HAQERs.
Orphan genes (aka taxon-specific / de novo genes) are protein-coding genes with no detectable homologues in other species. Human orphan genes were first reported in 2009 in a paper with the title, “Recent de novo origin of human protein-coding genes”.
Hundreds, possibly thousands have been detected. Some have demonstrated functions (development, reproduction, immunity, lineage-specific traits, and in some cases oncogenic roles). Most are still uncharacterized. Evolutionary geneticists believe that they arose de-novo from noncoding DNA, by rapid divergence and duplication.
Human Accelerated Regions (HARs) are short genomic regions that are highly conserved across vertebrates but show many substitutions in the human genome. Many act as developmental enhancers (especially in brain). They were first identified in a paper published in 2006.
They are typically non-coding and often involved in gene regulation. Multiple HARs function as enhancers in neural development. HAR perturbation can alter gene expression and has been linked to neurodevelopmental phenotypes.
Human Ancestor Quickly Evolved Regions (HAQERs) were first identified in 2022 using modern high-resolution comparative genomics.
These regions are believed to have undergone extremely fast mutation rates specifically in the hominin lineage after the split with chimpanzees. Evolutionary geneticists believe that they arose by short bursts of intense positive selection early in human evolution. They are enriched for bivalent/poised regulatory states and show experimental enhancer activity in neurodevelopmental contexts; HAQER variation is being linked to modern human traits (e.g., language) and neurodevelopmental disease risk.
I believe that these interesting features of the human genome present significant challenges to evolution, here I will consider orphan genes and HARs.
As stated above much has been written about the differences between human and chimpanzee genomes. The published percentage differences are probably not the best way to understand the differences, because there are functional differences which are much more significant.
First let’s look more at orphan genes. The term orphan gene is derived from the fact that there are orphan ORFs or ORFans. Put simply an ORF (open reading frame) is a stretch of DNA with a start codon and stop codon which is basically a gene coding for protein. ORFans or orphan genes (also known as taxon-specific or de novo genes) are protein-coding genes with no detectable homologues in other species.
Calling them orphans is not really accurate as it is not as if they have lost their mother (genes), they apparently never had a “mother”. There are no plausible ancestor genes in any supposed evolutionary ancestor. To date hundreds, possibly thousands have been detected. Some have demonstrated functions (development, reproduction, immunity, lineage-specific traits, and in some cases oncogenic roles). Most are still uncharacterized. Evolutionary geneticists believe that they arose de-novo from non-coding DNA, by rapid divergence and duplication. One recent publication (Oncogenic roles of young human de novo genes and their potential as neoantigens in cancer immunotherapy) covers interesting research on orphan genes. This paper describes 37 “young” de novo genes in humans within an updated genomic context. Their expression is “temporo-spatially” expanded across tumours. The fact that they are associated with tumours indicates that they are functionally important.
These are genes are not found in any other creatures and more importantly when looking at human orphan genes, there are no genes in ape genomes which could suggest how they arose by mutation of genes in a theoretical human ancestor. The origin of these uniquely human specific genes (and any orphan genes in other creatures) is difficult to explain within the existing neo-Darwinian paradigm. Evolutionists have to employ imagination to explain their origin. A good example is a paper written by Weisman “The origins and functions of de novo genes: against all odds?” Weisman cites Jacob who wrote “Evolution and Tinkering” in which he states that, “the probability that a functional protein would appear de novo by random association of amino acids is practically zero”. But then goes on to suggest ways in which de novo genes avoid Jacob’s “conundrum of improbability”. The proposed mechanisms are, as Weisman freely admits, “speculative” and the proposed causes are “highly conjectural”. Evolutionists are grasping at straws because to admit that orphan genes could not have evolved would mean giving up on evolution.
It seems much more probable that these are not de novo genes, but are designed human specific genes which contribute to making humans unique.
The second feature that challenges evolution is the existence of Human Accelerated Regions (HARs). These are short genomic regions that are highly conserved across vertebrates but show a “burst of substitutions” in the human lineage. The first description of HARs was published in 2006.
They are typically non-coding and often involved in gene regulation. Multiple HARs function as enhancers in neural / brain development. HAR perturbation can alter gene expression and has been linked to neurodevelopmental problems. Supporting evidence comes from rare polymorphisms in HARs which may account for 5% of consanguineous autism cases. Work on HAR enhancers is helping researchers to discover the genetic basis for some disease. See this publication for more information.
One of the first HARs to be discovered was given the name HAR1. It is active in the foetal brain and necessary for the proper development of the cerebral cortex.
According to evolutionists, human accelerated regions have “acquired” many nucleotide substitutions in the human genome since their divergence from the common ancestor with chimpanzees. This is surprising because they are highly conserved in other vertebrates. Nevertheless, evolutionists believe they arose by a process of adaptive evolution acting on random mutations.
The fact that they are highly conserved in non-humans suggests what evolutionists call strong purifying selection. This removes harmful mutations from a population. Given this, how did all the substitutions in human regulatory regions become fixed in the human genome? Stepwise mutation and fixation is only likely when each mutation confers some selective advantage. However, this seems unlikely given that changes to HARs have been linked to disease and would therefore be eliminated by purifying selection. Neutral substitutions may be possible but neutral substitutions they are unlikely to become fixed, because of the absence of any selective advantage.
The scale of the problem becomes even more obvious given that a typical human accelerated region, of about 100 to 300 base pairs, contains on the order of 10 to 20 human-specific nucleotide substitutions (commonly 8 to 25 substitutions). For example, HAR1 is 118 base pairs long and has 18 substitutions. This is surprising because these same regions in non-human vertebrates often show 0 to 1 substitutions, even though according to the evolutionary paradigm millions of years have elapsed. So 10 to 20 changes in approximately 6 million years of human evolution represents a dramatic acceleration.
I wanted to know the probability of this level of change, so I asked ChatGPT, “What is the probability of 18 specific substitutions in a DNA sequence of about 200 base pairs?” It replied with a stepwise calculation which I won’t copy and paste here. If you want the details, ask ChatGPT the same question for a typical HAR.
Chat GPT summarised the problem as follows:
“Under a neutral mutation model, the probability of observing 18 specific substitutions in a 200-bp region since the human–chimp split is on the order of 10 to minus 21 — essentially impossible without accelerated evolution”.
It then suggested that this problem could be overcome, by “relaxed constraint (loss of purifying selection)”. But even then, the probability was about 2 x 10 minus 9.
Then it suggested “strong positive selection (accelerated evolution)” could be the answer. ChatGPT then provided some other calculations based on a “selection friendly” model which brought the probability up to 10 minus 5, which is claimed was rare but plausible. That is one chance in 100 000, not very good odds (AI does hallucinate!). Then ChatGPT admitted that this was for any 18 substitutions and if we looked for 18 specific substitutions the probability dropped to 10 minus 14! But this outcome did not make ChatGPT a creationist. Rather it concluded that HARs are convincing evidence of adaptation and exactly what we expect from adaptative regulatory evolution! This can only happen if each substitution gives a selective advantage, which given that changes in the existing HARs are associated with disease is unlikely.
It seems that evolving one HAR is very improbable and the probability of evolving more than a thousand of them is essentially zero. This is why evolutionists invoke adaptive evolution. But is that plausible? Adaptive evolution happens when a genetic change is useful, so individuals carrying it leave more offspring, causing that change to spread. Adaptive evolution can in theory add useful changes to the genome whereas neutral evolution, when changes have no effect on fitness, is unlikely to retain changes because of random (stochastic) effects. But in the case of HARs there is a significant barrier to fixation. The sequences in question have, according to evolutionists, been subject to strong purifying selection, and are essentially the same across distant species. This is consistent with the idea that almost every alternative has been tested and rejected, because it reduced fitness. That is, any mutation in a HAR regulatory sequence of DNA would be harmful and not passed on because the individual would be less fit. Nevertheless, evolutionists claim that this problem can be overcome. One suggestion is that a harmful mutation could actually be beneficial if the environment changes. For this to work a mutation has to arise at the same time as an environmental change, which just happens to make the mutation beneficial. Improbable as it seems, evolutionists have to believe that, even though one beneficial mutation is unlikely, as many as 25 mutations in one HAR, all of which confer a selective advantage (or were at least neutral) became fixed in an ancestral human population.
This is why I would like to suggest that this did NOT happen. HARs bear the hallmarks of designed control mechanism, which are required to give us, among other things, big brains. Given what is known about genetics the only reasonable explanation is that humans had them from day one (or should I say day six!).
Click here for the blog post on HAQERs.
Much has been written about the differences between human and chimpanzee genomes. The published percentage difference ranges from about 2% to up to 15%. It all depends on how the comparison is done.
This blog post focuses on three very specific differences which have come to light in recent years. These are orphan genes, HARs and HAQERs.
Orphan genes (aka taxon-specific / de novo genes) are protein-coding genes with no detectable homologues in other species. Human orphan genes were first reported in 2009 in a paper with the title, “Recent de novo origin of human protein-coding genes”.
Hundreds, possibly thousands have been detected. Some have demonstrated functions (development, reproduction, immunity, lineage-specific traits, and in some cases oncogenic roles). Most are still uncharacterized. Evolutionary geneticists believe that they arose de-novo from noncoding DNA, by rapid divergence and duplication.
Human Accelerated Regions (HARs) are short genomic regions that are highly conserved across vertebrates but show many substitutions in the human genome. Many act as developmental enhancers (especially in brain). They were first identified in a paper published in 2006.
They are typically non-coding and often involved in gene regulation. Multiple HARs function as enhancers in neural development. HAR perturbation can alter gene expression and has been linked to neurodevelopmental phenotypes.
Human Ancestor Quickly Evolved Regions (HAQERs) were first identified in 2022 using modern high-resolution comparative genomics.
These regions are believed to have undergone extremely fast mutation rates specifically in the hominin lineage after the split with chimpanzees. Evolutionary geneticists believe that they arose by short bursts of intense positive selection early in human evolution. They are enriched for bivalent/poised regulatory states and show experimental enhancer activity in neurodevelopmental contexts; HAQER variation is being linked to modern human traits (e.g., language) and neurodevelopmental disease risk.
I believe that these interesting features of the human genome present significant challenges to evolution, here I will consider orphan genes and HARs.
As stated above much has been written about the differences between human and chimpanzee genomes. The published percentage differences are probably not the best way to understand the differences, because there are functional differences which are much more significant.
First let’s look more at orphan genes. The term orphan gene is derived from the fact that there are orphan ORFs or ORFans. Put simply an ORF (open reading frame) is a stretch of DNA with a start codon and stop codon which is basically a gene coding for protein. ORFans or orphan genes (also known as taxon-specific or de novo genes) are protein-coding genes with no detectable homologues in other species.
Calling them orphans is not really accurate as it is not as if they have lost their mother (genes), they apparently never had a “mother”. There are no plausible ancestor genes in any supposed evolutionary ancestor. To date hundreds, possibly thousands have been detected. Some have demonstrated functions (development, reproduction, immunity, lineage-specific traits, and in some cases oncogenic roles). Most are still uncharacterized. Evolutionary geneticists believe that they arose de-novo from non-coding DNA, by rapid divergence and duplication. One recent publication (Oncogenic roles of young human de novo genes and their potential as neoantigens in cancer immunotherapy) covers interesting research on orphan genes. This paper describes 37 “young” de novo genes in humans within an updated genomic context. Their expression is “temporo-spatially” expanded across tumours. The fact that they are associated with tumours indicates that they are functionally important.
These are genes are not found in any other creatures and more importantly when looking at human orphan genes, there are no genes in ape genomes which could suggest how they arose by mutation of genes in a theoretical human ancestor. The origin of these uniquely human specific genes (and any orphan genes in other creatures) is difficult to explain within the existing neo-Darwinian paradigm. Evolutionists have to employ imagination to explain their origin. A good example is a paper written by Weisman “The origins and functions of de novo genes: against all odds?” Weisman cites Jacob who wrote “Evolution and Tinkering” in which he states that, “the probability that a functional protein would appear de novo by random association of amino acids is practically zero”. But then goes on to suggest ways in which de novo genes avoid Jacob’s “conundrum of improbability”. The proposed mechanisms are, as Weisman freely admits, “speculative” and the proposed causes are “highly conjectural”. Evolutionists are grasping at straws because to admit that orphan genes could not have evolved would mean giving up on evolution.
It seems much more probable that these are not de novo genes, but are designed human specific genes which contribute to making humans unique.
The second feature that challenges evolution is the existence of Human Accelerated Regions (HARs). These are short genomic regions that are highly conserved across vertebrates but show a “burst of substitutions” in the human lineage. The first description of HARs was published in 2006.
They are typically non-coding and often involved in gene regulation. Multiple HARs function as enhancers in neural / brain development. HAR perturbation can alter gene expression and has been linked to neurodevelopmental problems. Supporting evidence comes from rare polymorphisms in HARs which may account for 5% of consanguineous autism cases. Work on HAR enhancers is helping researchers to discover the genetic basis for some disease. See this publication for more information.
One of the first HARs to be discovered was given the name HAR1. It is active in the foetal brain and necessary for the proper development of the cerebral cortex.
According to evolutionists, human accelerated regions have “acquired” many nucleotide substitutions in the human genome since their divergence from the common ancestor with chimpanzees. This is surprising because they are highly conserved in other vertebrates. Nevertheless, evolutionists believe they arose by a process of adaptive evolution acting on random mutations.
The fact that they are highly conserved in non-humans suggests what evolutionists call strong purifying selection. This removes harmful mutations from a population. Given this, how did all the substitutions in human regulatory regions become fixed in the human genome? Stepwise mutation and fixation is only likely when each mutation confers some selective advantage. However, this seems unlikely given that changes to HARs have been linked to disease and would therefore be eliminated by purifying selection. Neutral substitutions may be possible but neutral substitutions they are unlikely to become fixed, because of the absence of any selective advantage.
The scale of the problem becomes even more obvious given that a typical human accelerated region, of about 100 to 300 base pairs, contains on the order of 10 to 20 human-specific nucleotide substitutions (commonly 8 to 25 substitutions). For example, HAR1 is 118 base pairs long and has 18 substitutions. This is surprising because these same regions in non-human vertebrates often show 0 to 1 substitutions, even though according to the evolutionary paradigm millions of years have elapsed. So 10 to 20 changes in approximately 6 million years of human evolution represents a dramatic acceleration.
I wanted to know the probability of this level of change, so I asked ChatGPT, “What is the probability of 18 specific substitutions in a DNA sequence of about 200 base pairs?” It replied with a stepwise calculation which I won’t copy and paste here. If you want the details, ask ChatGPT the same question for a typical HAR.
Chat GPT summarised the problem as follows:
“Under a neutral mutation model, the probability of observing 18 specific substitutions in a 200-bp region since the human–chimp split is on the order of 10 to minus 21 — essentially impossible without accelerated evolution”.
It then suggested that this problem could be overcome, by “relaxed constraint (loss of purifying selection)”. But even then, the probability was about 2 x 10 minus 9.
Then it suggested “strong positive selection (accelerated evolution)” could be the answer. ChatGPT then provided some other calculations based on a “selection friendly” model which brought the probability up to 10 minus 5, which is claimed was rare but plausible. That is one chance in 100 000, not very good odds (AI does hallucinate!). Then ChatGPT admitted that this was for any 18 substitutions and if we looked for 18 specific substitutions the probability dropped to 10 minus 14! But this outcome did not make ChatGPT a creationist. Rather it concluded that HARs are convincing evidence of adaptation and exactly what we expect from adaptative regulatory evolution! This can only happen if each substitution gives a selective advantage, which given that changes in the existing HARs are associated with disease is unlikely.
It seems that evolving one HAR is very improbable and the probability of evolving more than a thousand of them is essentially zero. This is why evolutionists invoke adaptive evolution. But is that plausible? Adaptive evolution happens when a genetic change is useful, so individuals carrying it leave more offspring, causing that change to spread. Adaptive evolution can in theory add useful changes to the genome whereas neutral evolution, when changes have no effect on fitness, is unlikely to retain changes because of random (stochastic) effects. But in the case of HARs there is a significant barrier to fixation. The sequences in question have, according to evolutionists, been subject to strong purifying selection, and are essentially the same across distant species. This is consistent with the idea that almost every alternative has been tested and rejected, because it reduced fitness. That is, any mutation in a HAR regulatory sequence of DNA would be harmful and not passed on because the individual would be less fit. Nevertheless, evolutionists claim that this problem can be overcome. One suggestion is that a harmful mutation could actually be beneficial if the environment changes. For this to work a mutation has to arise at the same time as an environmental change, which just happens to make the mutation beneficial. Improbable as it seems, evolutionists have to believe that, even though one beneficial mutation is unlikely, as many as 25 mutations in one HAR, all of which confer a selective advantage (or were at least neutral) became fixed in an ancestral human population.
This is why I would like to suggest that this did NOT happen. HARs bear the hallmarks of designed control mechanism, which are required to give us, among other things, big brains. Given what is known about genetics the only reasonable explanation is that humans had them from day one (or should I say day six!).
Click here for the blog post on HAQERs.
