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Monday, May 27, 2024

Telomere length in humans

Telomeres are repetitive DNA sequences at the ends of chromosomes. In humans, the repeat sequence is TTAGGG. The purpose of telomeres is to protect the ends of the chromosomes from shortening after DNA replication [Telomeres].

Telomeres are just one of many functional DNA elements in the human genome. The average length of human telomeres was long thought to be about 10 kb and since there are 24 distinct chromosomes in the human genome this amounts to about 480 kb of telomere sequence or about 0.015% of the human genome. With the advent of new sequencng technology it is now possible to generate long reads of DNA sequence and this has led to a somewhat shorter estimate of telomere length (Karimian et al., 2024). The figure from thier paper shows that the average length of telomeres gets shorter with age but the starting length in newborns (cord DNA) is about 8 kb instead of 10 kb. The authors explain why their sequencing technique is likely to give more accurate results than the earlier estimates.

This doesn't make much difference to the previous estimate but I thought I'd post an update since I overestimated the contribution of telomeres in my book and I made a calculation error in a previous post [Telomeres].

If we use 8 kb as the average length, then that means a total of 8 × 2 × 24 = 384 kb or 0.012% of the standard human genome, which includes 22 autosomes and both sex chromsomes.

Image Credit: The image shows human chromosomes (blue) labelled with a telomere probe (yellow), from Christopher Counter at Duke University.

Karimian, K., Groot, A., Huso, V., Kahidi, R., Tan, K.-T., Sholes, S., Keener, R., McDyer, J.F., Alder, J.K., Li, H., Rechtsteiner, A. and Greider, C. (2024) Human telomere length is chromosome end–specific and conserved across individuals. Science 384:533-539. [doi: 10.1126/science.ado0431]

Tuesday, May 21, 2024

University of Toronto President explains why the Occupy for Palestine demands are unreasonable and unacceptable

The Occupy for Palestine protestors have occupied part of the campus of the University of Toronto. The protestors are making two demands on the university.

  • “terminate all partnerships with Israeli academic institutions that operate in the Occupied Palestinian Territories, or sustain the apartheid policies, occupation and illegal settlement of these territories.”
  • “divest its endowment, pension fund, and other financial holdings from all companies that provide Israel with military goods or services which sustain the Israeli apartheid, occupation and illegal settlement of the Palestinian Territories, as well as the ongoing attacks on Gaza.”

The President of the University of Toronto, Meric Gertler, has responded to these demands with a letter sent to the members of Occupy for Palestine [President Meric Gertler’s response to members of Occupy for Palestine].

With respect to the first demand, President Gertler points out that the university has a history of opposition to academic boycotts.

Such demands are antithetical to the University’s firm conviction that the best way to protect human rights is by staunchly defending and promoting academic freedom, freedom of expression, and the unfettered circulation of ideas within the global scholarly community. We have consistently emphasized that it is both inappropriate and, ultimately, counterproductive to single out academics working or studying in a particular country, and to hold them accountable for the actions or policies of their country’s government. Faculty and students are often among the most trenchant critics of their own government’s policies or actions. Events over the past year confirm that Israeli academics – as well as university leaders – have been amongst the most vociferous critics of the current government and its policies.

For this reason, the university rejects the Occupy for Palestine's first demand.

The second demand is unreasonable because the University does not directly control the pension fund; those investments are controlled by a Board of Trustees, some of whom are appointed by staff and faculty because a large percentage of the pension fund is their money. Also, the pension fund is a joint fund with the University of Guelph and Queen's University. Similarly, with respect to the endowment fund, the University does not directly control direct investments in companies so it cannot comply with the demand even if it wished to.

However, notwithstanding those practicalities, there are fundamental principles at stake that need to be addressed.

... the University’s Policy on Social and Political Issues with Respect to University Divestment notes in its opening Preamble that “As a general matter, the University does not take positions on social or political issues apart from those directly pertinent to higher education and academic research.” Accordingly, “the University will not consider proposals for restrictions on its investments that require the institution to take sides in matters that are properly the subject of ongoing academic inquiry and debate.” It further notes, as a corollary, that the University’s response to any requests for divestment “must be governed by the fundamental place of diversity of opinion within its community. Except in those situations in which the University must settle on an answer to controversial questions about how best to achieve its academic mission, the University risks abandoning its core values if it takes sides in ongoing debates and is perceived to be advancing a specific political or social position.”

This is consistent with the Chicago Principles on free expression and the Kalven Report on the University's role in political and social action. Meric Gertler does not specifically mention the Kalven Report from the University of Chicago but it's clear that it forms the basis of the University of Toronto's position. For that reason, and because that position is not widely understood, I quote from the report.

A university has a great and unique role to play in fostering the development of social and political values in a society. The role is defined by the distinctive mission of the university and defined too by the distinctive characteristics of the university as a community. It is a role for the long term.

The mission of the university is the discovery, improvement, and dissemination of knowledge. Its domain of inquiry and scrutiny includes all aspects and all values of society. A university faithful to its mission will provide enduring challenges to social values, policies, practices, and institutions. By design and by effect, it is the institution which creates discontent with the existing social arrangements and proposes new ones. In brief, a good university, like Socrates, will be upsetting.

The instrument of dissent and criticism is the individual faculty member or the individual student. The university is the home and sponsor of critics; it is not itself the critic. It is, to go back once again to the classic phrase, a community of scholars. To perform its mission in the society, a university must sustain an extraordinary environment of freedom of inquiry and maintain an independence from political fashions, passions, and pressures. A university, if it is to be true to its faith in intellectual inquiry, must embrace, be hospitable to, and encourage the widest diversity of views within its own community. It is a community but only for the limited, albeit great, purposes of teaching and research. It is not a club, it is not a trade association, it is not a lobby.

Since the university is a community only for these limited and distinctive purposes, it is a community which cannot take collective action on the issues of the day without endangering the conditions for its existence and effectiveness. There is no mechanism by which it can reach a collective position without inhibiting that full freedom of dissent on which it thrives. It cannot insist that all of its members favor a given view of social policy; if it takes collective action, therefore, it does so at the price of censuring any minority who do not agree with the view adopted. In brief, it is a community which cannot resort to majority vote to reach positions on public issues.

I am a University of Toronto retired professor and I fully support the position of the University President. The university cannot and should not take a position on social issues. I fully support the rights of students and faculty to express their personal views on such issues. For example, we may protest the behavior of the Israel government, of Hamas, the governments of Russia or Ukraine, and even, especially, our own government. Those are all legitimate targets of protest. The university is not a legitimate target. The university is not our enemy.

Sunday, May 05, 2024

Junk DNA debate: Casey Luskin vs Dan Stern Cardinale

Here's a link to the junk DNA debate between Dan Stern Cardinale and Casey Luskin. The debate took place on May 2, 2024.

I mentioned in a previous post that Luskin should have been called out on his repeated attempts to equate junk DNA with non-coding DNA. This allowed him to portray all non-coding functions as evidence against junk DNA. [Casey Luskin posts misleading quotes about junk DNA].

There are several other things that I would have done differently. I would have made it clear that 10% of the genome is functional and we don't know the function of some of that fraction. Thus, all newly discovered functional regions could still fit into the 10% and 90% of the genome is still junk. Every time Casey mentions a new function he should have been challenged to specify exactly what percentage of the genome he is referring to. (Dan tried to do this but he was too nice, and let Casey off the hook.)

The idea here is to make it clear to viewers that recent discoveries of functional regions do not affect the idea that most of our genome is junk.

I would also attempt to get Casey to admit that there's a scientific controversy over junk DNA so there are many papers defending junk DNA and criticizing the arguments of junk DNA opponents. For every quotation from a scientist who opposes junk, there's an equally significant quotation from one who supports junk. Why does Casey only quote scientists who agree with him? Is this cherry-picking? Is selectively rattling off quotations and references from people who agree with you a reasonable way to have a serious scientific debate?

I think the arguments over transcripts should begin with presenting all the scientific evidence that spurious transcripts exist - for example, random DNA sequences inserted into a cell nucleus are transcribed and spurious transcription is easily documented in well-studied organisms such as bacteria and yeast. The characteristics of spurious transcription are that the transcripts are present in very small amounts, that they are rapidly degraded, that they come from regions of the genome that are not under purifying selection, and they are cell/tissue specific. So what is the most reasonable explanation when you look at such transcripts?

Casey Luskin's attempt to avoid the best explanation (spurius transcription) is a classic example ad hoc rescue and it might have been useful to point this out to viewers.

Regulation is not new. There was serious discussion and debate over the amount of the genome devoted to regulation back in the late 1960s when the concept of junk DNA was first proposed. Casey should have been challenged to state what percentage of the genome is devoted to regulation and if he comes up with an unreasonable number he should have to give examples of many well-studied genes that have been shown to have that level of regulation. (Hint: There aren't any.) All of the detailed work on the regulation of dozens of specific human genes has shown that you don't need more than a few transcription factor binding sites to control expression. Is there any reason to suppose that the other genes require ten or a hundred times more regulatory sequences to control expression?

What is the trend line? Ever since the ENCODE publicity disaster of 2012 there has been a flood of papers defending junk DNA and the data supporting junk DNA is now stronger that it has ever been because we now know from hundreds of thousands of human genome sequences that only about 10% is under purifying selection. There have also been a lot of papers fleshing out the 10% of the genome that's functional. There have only been a handful of papers published in the past ten years that seriously attempt to present evidence that most of our genome is functional. I would have challenged Casey to come up with a single scientific publication in the past ten years claiming, with supporting data, that most of the genome is functional.

Saturday, May 04, 2024

Casey Luskin posts misleading quotes about junk DNA

On Thursday May 2, 2024, Casey Luskin and Dan Stern Cardinale debated junk DNA on the YouTube channel "The NonSequitor Show." David Klinghoffer thinks that this debate went very well for the ID side [Debate: Casey Luskin Versus Rutgers Biologist Dan Cardinale, Thursday, May 2]. I agree with Klinghoffer; Luskin did an excellent job of promoting his case because many of his statements and claims were not challenged effectively.

I'll be putting up a separate post on the debate but for now I'd like to address an article by Casey Luskin that he posted before the debate as preparation for what he was going to say. The article consists of a bunch of quotes from prominent scientists about junk DNA [“Junk DNA” from Three Perspectives: Some Key Quotes]. Here are the three perspectives, according to Luskin.

Category 1: Quotes from evolutionists claiming (or repeating the widespread belief) that non-coding DNA is “junk” and has no function.

Some of the quotes represent the actual position of junk DNA proponents but Luskin has also picked out stupid quotes from scientists who think, incorrectly, that all non-coding DNA is junk. This is deliberate as we will see below.

Category 2: Early quotes from intelligent design theorists predicting function for non-coding “junk” DNA.

Luskin builds the case for function in non-coding DNA by quoting religious scientists who "predict" that there will be functional DNA in non-coding regions of the genome. This is disingenuous at best because Luskin knows full well that from the very beginning of the scientific debate we knew about functional non-coding DNA. It was never the case that all non-coding DNA was assumed to be junk.

Category 3: Quotes from mainstream scientific sources saying that we’ve experienced a shift in our thinking that junk DNA actually has function.

Many of these quotes are from scientists announcing that some non-coding DNA has a function. They support Luskin's false claim that all non-coding DNA was thought to be junk and the discovery of functional regions of non-coding DNA has resulted in a "paradigm shift" in our view of the human genome.

Casey Luskin should not have been allowed to get away with equating junk DNA and non-coding DNA in the debate. He should have been challenged to retract that false claim at the very beginning of the debate and called out whenever he used the term "non-coding DNA" during the debate.