Mutations in Humans: Calculating Human Gene Code Change Rate

[heliocentricprose]

On average, what percent of the human genecode changes each generation? I know there's somesort of mutation rate, but I haven't studied biology for several years and I'm not exactly sure how to calculate it.

 

[jim mcnamara]

The mutation rate for a generation of cells is given as
$$alpha=\frac{h}{N}$$
Where h is the number of mutation observed and N is the total number of cell divisions.

If you tranlsate that to humans, you are interested in the rate as a function of the number of new mutations showing up in the next generation. However, there are lots of problems with this. A large number of spontaneous mutations are fatal to embryo development, for example. So unless you analyzed every premature birth for new defects, you'd miss them. This isn't practical or ethical.

And I have no idea how you could find all mutations - we're diploid, so a recessive mutation has a large probability of not displaying a trait.

 

[jim mcnamara]

See this paper:
http://www.genetics.org/cgi/content/full/156/1/297

 

[heliocentricprose]

See this paper:
http://www.genetics.org/cgi/content/full/156/1/297

"calculated that the per locus rate of mutation for hemophilia in humans is 10^-5 per generation"

"Comparisons of pseudogenes and of synonymous sites between humans and chimpanzees have suggested mutation rates on the order of 10^-8"

10^-5
10^-8

What do these numbers represent? Base pair substitutions, mutation events?

 

[jim mcnamara]

Nucleotide changes - for a single allele (DNA sequence that codes for one enzyme). eg. a Thymine becomes an Adenine, for example.

 

[heliocentricprose]

So this means there are 1/100000000 nucleotide changes per generation?

 

[jim mcnamara]

For one allele, or "one gene". Humans have circa 100,000 genes with sometimes hundreds of alleles (possible gene variations for a given locus).

[lousy assumption alert]

So, multiply your number times 100,000 and you have a guesstimate of the mutation rate in humans per generation. Since 10^-5 times 10^5 =1
then the mutation rate over all genes - based on the paper - in humans is about one point mutation (that's what a nucloetide change is) per generation somewhere in all of the human genome.

[/lousy assumption alert]
There are other types of mutations, crossovers, deletions, insertions etc.
(a lot of which are fatal) so it's hard to know the true rate based on looking at only live born people. I do know that Thompson & Thompson Medical Genetics indicates that for 100 live male births there are ~130 conceptions. The spontaeous abortion rates for female fetuses is lower.
(This is very old data)