Why is it assumed that the absence of lactase is the ancestral state?

[Islam (islam emam)]

Why is it assumed that the absence of lactase is the ancestral state?, why is lactase persistence not the ancestral state, then a mutation occurred that reduced its production after weaning?

[Rumraket (Mikkel R.)]

In no mammal species do they breastfeed into adulthood? Over your life-history you begin by getting milk from your mother, as you are an infant. But as you grow up you stop breastfeeding. Since milk would no longer be a staple in your diet(prior to domestication of species we obtain milk from), there’s no reason for you to keep producing enzymes that break down lactose. For millions of years our ancestors did not have domesticated goats and cows to harvest milk from, so when you grew up you stopped getting milk in your diet relatively early.

All our closest relatives do not breastfeed into adulthood, and none of them have domesticated cows or goats. That implies the ancestral state is that lactase production is eventually turned off as you grow up. Then eventually on the human lineage we domesticated cows and goats and could get milk in our diets well into adulthood. It then became advantageous to keep the gene turned on for your entire life. That’s why it’s a derived instead of ancestral trait.

So you see, it’s not an assumption. It’s an inference from the evidence.

[T_aquaticus]

@Islam

Why is it assumed that the absence of lactase is the ancestral state?

Just to clear up a few terms, nearly all humans produce lactase as children. If we didn’t then we couldn’t use the lactose in milk.

The phenotype you are referring to is lactase persistence, the ability to keep producing lactase throughout one’s life. This is due to mutations upstream of the coding region of lactase which alters its expression through life.

@Rumraket does a good job of explaining the ecological reasons why lactase persistence would be a more recent adaptation with the ancestral state being lactase expression just in childhood.

The genetics kind of seal the deal.

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [−13910T* (rs4988235), −13907G* (rs41525747), −13915G* (rs41380347), −14009G* (rs869051967) and −14010C* (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the ‘Old World’ and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.
World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection - PMC

All of this comes with the caveat of “if I am understanding the paper and concepts correctly”.

First, there are many different alleles for lactase persistence, and they are geographically distributed. This would indicate that the alleles originated in these populations after migration out of Africa. This would mean the lactase persistence allele is not the ancestral state. Also mentioned in the paper is the sequencing of ancient DNA in which the lactase persistence allele only appears recently (<5,000 years ago in some cases).

Second, the sequence surrounding the mutations responsible for lactase persistence is also very similar between those with the same allele. This would indicate a recent selective sweep that has not allowed time for the accumulation of other mutations in the surrounding sequence. However, there are differences in recombination rates that may cloud these findings.

[Islam (islam emam)]

However, this is not evidence that the absence of lactase was also the case for our human ancestors. I believe the strongest evidence would be to examine the DNA of as many ancient humans as possible and demonstrate that they lacked the lactase persistence mutation.

[T_aquaticus]

@Islam

I believe the strongest evidence would be to examine the DNA of as many ancient humans as possible and demonstrate that they lacked the lactase persistence mutation.

The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought. [emphasis mine]
Population genomics of Bronze Age Eurasia - PubMed

The strongest signal of selection is at the SNP (rs4988235) responsible for lactase persistence in Europe15,16. Our data (Fig. 3) strengthens previous reports that an appreciable frequency of lactase persistence in Europe only dates to the last four thousand years3,5,17. The allele’s earliest appearance in our data is in a central European Bell Beaker sample (individual I0112) that lived between approximately 2300 and 2200 BCE.
Genome-wide patterns of selection in 230 ancient Eurasians - PMC

[Rumraket (Mikkel R.)]

@Islam

However, this is not evidence that the absence of lactase was also the case for our human ancestors.

Since we know our ancestors did not have domesticated animals that produced milk, and none of our closely related cousin species have domesticated animals that produce milk, and since we all (both we and all our closest relatives) stop breastfeeding early and a subpopulation of humans is the only outlier, that is in fact evidence that lactase persistence is a derived trait that evolved in the human lineage.

[Islam (islam emam)]

thank you @T_aquaticus , the presence of SNPs (single nucleotide polymorphisms) in the lactase gene, along with the absence of mutations in the DNA of ancient humans, strongly suggests that the ability to digest lactose as an adult is a relatively recent human adaptation. The ancestral condition, therefore, is the absence of lactase persistence, which means that lactose was likely not a significant part of the diet for early humans.

[Islam (islam emam)]

I understood. The presence of agriculture led to the selection of this trait and therefore it spread
Thankss @Rumraket

[Rumraket (Mikkel R.)]

Thank you, and you’re welcome!

[Giltil (Gilbert Thill)]

@Rumraket

Then eventually on the human lineage we domesticated cows and goats and could get milk in our diets well into adulthood. It then became advantageous to keep the gene turned on for your entire life

Given that the presence of the mutations that confer lactase persistence doesn’t seem to correlate with milk consumption, your simple scenario probably doesn’t reflect the reality.

Much Ado About Lactase Persistence | Evolution News

[T_aquaticus]

@Giltil

Given that the presence of the mutations that confer lactase persistence doesn’t seem to correlate with milk consumption, your simple scenario probably doesn’t reflect the reality.

The ENV article gets this very wrong:

The gene for lactase is about fifty-thousand nucleotides long, is composed of 17 exons, and has a one-thousand nucleotide promoter region preceding it. On the other hand, mutations that cause LP are single-nucleotide changes (any of several distinct ones will work) — just one (count ‘em, one) unit out of more than fifty thousand. What’s more, the change results in what in Darwin Devolves I termed a “loss-of-functional-coded-element” (loss-of-FCT). The mutation apparently (the situation is still not nailed down) destroys a pre-existing binding site near the gene for a regulatory protein that once switched off the gene at the appropriate developmental age.

This is false. The mutations result in a new binding site for a transcription factor:

Two phenotypes exist in the human population with regard to expression of lactase in adults. Lactase non-persistence (adult-type hypolactasia and lactose intolerance) is characterized by a decline in the expression of lactase-phlorizin hydrolase (LPH) after weaning. In contrast, lactase-persistent individuals have a high LPH throughout their lifespan. Lactase persistence and non-persistence are associated with a T/C polymorphism at position -13,910 upstream the lactase gene. A nuclear factor binds more strongly to the T-13,910 variant associated with lactase persistence than the C-13,910 variant associated with lactase non-persistence. Oct-1 and glyceraldehyde-3-phosphate dehydrogenase were co-purified by DNA affinity purification using the sequence of the T-13,910 variant. Supershift analyses show that Oct-1 binds directly to the T-13,910 variant, and we suggest that GAPDH is co-purified due to interactions with Oct-1. Expression of Oct-1 stimulates reporter gene expression from the T and the C-13,910 variant/LPH promoter constructs only when it is co-expressed with HNF1alpha. Binding sites for other intestinal transcription factors (GATA-6, HNF4alpha, Fox and Cdx-2) were identified in the region of the -13,910 T/C polymorphism. Three of these sites are required for the enhancer activity of the -13,910 region. The data suggest that the binding of Oct-1 to the T-13,910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population.
T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro - PubMed

This is a new positive function, not a loss of function as claimed at ENV.

[Rumraket (Mikkel R.)]

@Giltil

Given that the presence of the mutations that confer lactase persistence doesn’t seem to correlate with milk consumption, your simple scenario probably doesn’t reflect the reality.

Assuming that statement is correct(massive grain of salt for anything written on EN&V), it still straightforwardly doesn’t follow that what I describe is incorrect. It is not required that today the geographical areas where the mutations are most prevalent, should also correlate with today’s degree of milk consumption.

[riversea (Learning a New Language)]

@Islam

Why is it assumed that the absence of lactase is the ancestral state?, why is lactase persistence not the ancestral state, then a mutation occurred that reduced its production after weaning?

I’m curious if all people will be able to digest milk if they can drink milk from animals that eat nutritious food, and the milk they drink from animals hasn’t been processed, and the fat and other nutrients in the milk aid in digestion for all adults. As a result, all adults can digest milk.

If cows farts stink up an entire town, how can that cow, who can’t even digest an unhealthy way of eating, produce milk that some adults can’t digest?

[Giltil (Gilbert Thill)]

Regarding the molecular mechanism underlying the lactase persistence phenotype in human, the paper you point to is old (2005) and not very convincing. In fact, nearly 2 decades later, the situation remains unclear. But the think to bear in mind is that the expression of the LPH enzyme is tightly regulated in mammals, being silenced after weaning. How this timely silencing system operates is not really understood, but one thing seems clear, the lactate persistence phenotype is more likely to result from the destruction of some element of the silencing system than from the creation of a new function.

[Giltil (Gilbert Thill)]

@Rumraket

It is not required that today the geographical areas where the mutations are most prevalent, should also correlate with today’s degree of milk consumption.

But, for your scenario to be correct, it is required that a correlation exists
between milk consumption in antiquity and the presence of the lactase mutation in a region But according to the study Behe refers to, it doesn’t seem to be the case.

[T_aquaticus]

@Giltil

Regarding the molecular mechanism underlying the lactase persistence phenotype in human, the paper you point to is old (2005) and not very convincing.

Why is it not convincing? Be specific.

@Giltil

In fact, nearly 2 decades later, the situation remains unclear.

It is as clear as day in the paper I supplied.

@Giltil

But the think to bear in mind is that the expression of the LPH enzyme is tightly regulated in mammals, being silenced after weaning. How this timely silencing system operates is not really understood, but one thing seems clear, the lactate persistence phenotype is more likely to result from the destruction of some element of the silencing system than from the creation of a new function.

I already supplied evidence to the contrary.

[T_aquaticus]

@riversea

I’m curious if all people will be able to digest milk if they can drink milk from animals that eat nutritious food, and the milk they drink from animals hasn’t been processed, and the fat and other nutrients in the milk aid in digestion for all adults. As a result, all adults can digest milk.

It has to do with the presence of lactose that hasn’t been broken down. The correlation between lactose intolerance and the mutations is pretty tight.

[Rumraket (Mikkel R.)]

@T_aquaticus

@Giltil

Regarding the molecular mechanism underlying the lactase persistence phenotype in human, the paper you point to is old (2005) and not very convincing.

Why is it not convincing? Be specific.

I’m going to have to second this. Why would the papers date be relevant at all (is there something wrong with the assays done in 2005), and how do these assays fail to demonstrate a binding interaction?

[T_aquaticus]

@Rumraket

I’m going to have to second this. Why would the papers date be relevant at all (is there something wrong with the assays done in 2005), and how do these assays fail to demonstrate a binding interaction?

Apparently, @Giltil would have fully accepted the paper in 2006, kind of liked it in 2012, but totally rejects the paper now, even though not a word or number in the paper has changed. Quite funny, actually.

[Roy (30-year veteran)]

Nah, he’d have rejected it in 2006 too. He’d simply have omitted the comment about its age, giving instead some other equally ridiculous excuse.