Are the number of base pairs in a given chromosome same between different individuals?

Question

This is a basic question but I couldn't find an answer through a web search; hopefully this is the right place to ask. Is the number of base pairs in a particular chromosome the same in all individuals? For example if I take an X-chromosome from two random humans would I count exactly 155,270,560 base pairs in both cases? or are there mutations that would make one longer than the other? If they're not exactly the same, what's the range in length variation?

Answer 1

Welcome to Biology.SE.

if I take an X-chromosome from two random humans would I count exactly 155,270,560 base pairs in both cases

No, you would probably not find the exact same number of base pairs because mutations do no only change one nucleotide to another (what we call a substitution) but sometimes add or delete few (or sometimes many) nucleotides.

note, btw that you don't need to take two different individuals, you can just consider the two X chromosomes of a female (or any other pair of chromsom in any gender) and find this difference in the length of chromosomes.

what's the range in length variation?

Good question (+1)!

Telomere issue

Before I start, I want to make clear that I consider the length of those chromosomes at the moment of conception. Chromosomes will vary in length during the lifetime due to telomere reduction. I will not consider this in the following calculations. Also, some mutations directly introduce (or delete) a large number of nucleotides (transposable elements for example), I am not considering those mutations here, assuming they are rare in comparison to to single insertions and single deletions (this assumption might not hold!). So please really take the following with a grain of salt.

Let's make some messy calculations

In classical theoretical population genetics, we tend to consider mostly substitutions. But I can maybe try to make some extrapolation out of this work if you allow me to make some strong assumptions, use poor estimates of actual true values and using some non-rigorous mathematics! This is going to be ugly and not extremely trustful $\ddot \smile $.

Not explaining why this is true (it is a result coming from Coalescent Theory), the expected number of pairwise differences between two neutral sequences for a diploid population is $E[\pi] = 4\cdot N\cdot \mu$ (quite an impressively simple result), where $N$ is the population size (assuming panmictic population) and $\mu$ is the mutation rate for the whole sequence. Assuming a constant per site mutation rate of $\mu_s = 10^{-9}$. Knowing the length of the sequence of interest (chromosom X) $L ≈ 1.55 \cdot 10^8 $, the mutation rate for the whole sequence is $\mu = L\cdot \mu_s = 0.155$. Let's consider a population size of $N = 5 \cdot 10^7$ (the equations assume a panmictic population so I just took some value that felt more or less reasonable to me much smaller than the actual worldwide population size). Therefore the total number of substitutions should be $E[\pi] = 4 \cdot 5 \cdot 10^7 \cdot 0.155 ≈ 10^7$.

Now, let's assume that only a fraction of $\frac{1}{100}$ of the mutations bring variation in the number of nucleotides, we might want consider the value $\frac{1}{100} \cdot 10^7 = 10^3$. And because a mutation that deletes a nucleotide from a long sequence will rather diminish the number of variant in sequence length that increasing it, let's say that will divide this number by 10!... so I'd say that two typical X chromosome would differ in length by about 100 nucleotides.

I am sure that with some work one can come up with more rigorous calculations and a more accurate expectation. Intuitively, the result of 100 nucleotides doesn't sound totally crazy (it is not 1 nor 10^6 at least).

Also, one could probably use available sequence data to estimate this value.

Answer 2

You would never count 155,270,560 bp in X chromosome. 7 years ago gapless (status complete) human genome did not exist, this is from GRCh37.p13. That is info about genome that had fake gaps inserted. But in January 2022 we finally got all genome (Y chromosome too) and perfect number is 154,259,566. All other numbers for other chromosomes are in wikipedia taken from here. https://www.ncbi.nlm.nih.gov/assembly/GCA_009914755.4

P.S. You literally did not know the basic of it. 155,270,560 is a number with inserted fake gaps, you can see it here: https://www.ncbi.nlm.nih.gov/grc/human/data?asm=GRCh37.p13 The number you wanted was on tab Ungapped lengths, at the time it was 151,100,560. So that means at the time of GRCh37.p13 some of it was not known.

Answer 3

Are there mutations that would make one longer than the other? If they're not exactly the same, what's the range in length variation?

As pointed out in the other answers, there can be mutations that change the length of the DNA between individuals and even single cells of the same tissue.

There are different processes that can change the genome length. The most common ones are:

• micro-indels (insertion and deletions) or sometimes just simply indels: Small changes (1-50nt) ^[1]. Usually happen during imperfect DNA repair via Non-Homologous End Joining post a double-strand break.
• Copy number variation (CNV): bigger variations that generally happen due to deletions and duplications of DNA segments >50bp.
• Transposon expansion
• Chromosomal translocations

We can ignore microindels and chromosomal translocations for the moment because the former impart only a small change to the genome size and the latter are usually rare and in most cases, are extremely deleterious.

With a stringent mapping, CNVs are known to cause 4.8% variation in the size of the human genome ^[2]. It is to be noted that this information does not account for the frequency of the changes; this is just a sort of maximum limit. It can also be noted that deletions have a greater contribution to variation compared to insertions.

LINE-1 retrotransposons are known to be quite active in the human genome. They accounts for ~17% of the human genome and are one of the major sources of inter-individual variation ^[3]. They are especially noted for promoting somatic heterogeneity in differentiating neurons ^[4]. Since LINEs expand by copy-pasting, their activity is correlated with increase in genome size. Transposon activity is generally suppressed in germ cells by a class of small non-coding RNAs called piRNAs ^[5].

I haven't found an article that exactly describes the variance in the genome size due to LINE-1 or other transposable elements. I'll add a reference if I find one.