evolution of sex biased genes

• males and females differ in physical traits and behavior

• occurs in most higher eukaryotes.

• male: shows extravagant or exaggerated secondary sexual characteristics (e.g. the peacock’s tail).

  -> Often these traits appear to be deleterious to the individual’s survival.

a) Male-male competition – males use these traits to compete with each other for food, territory, access to females, etc.

b) Female choice – females prefer to mate with males with “attractive” phenotypes.

In general, traits involved in male-reproduction (either directly or indirectly) tend to evolve fast.

That is, they show extensive changes between species.

expressed at a higher level in one sex than in the other.

The expression difference is usually determined from male vs. female microarray or RNA-seq experiments.

Fold change or stat test

• For example, using a 2-fold cutoff:

M/F = Male/female expression ratio

M/F > 2 = male-biased gene (MBG)

M/F < 0.5 = female-biased gene (FBG)

0.5 < M/F < 2 = unbiased gene (UBG)

• when in log2 scale:

log2(M/F) > 1 = MBG

log2(M/F) < –1 = FBG

–1 < log2(M/F) < 1 = UBG

depends on thresholds and criteria

2000 MBG

2000 FBG

9000 UBG

-> 30% of Drosophila genes are sex-biased by the 2-fold criterion

even larger sex biased share when using stat test:

meta-analysis and (FDR) of 5%:

2800 MBG

4000 FBG

-> 50%

Classification possible for about 85% of the genes as sex-biased

MBG tend to have a stronger expression bias than FBG:

The average M/F for MBG = 6,

while the average F/M for FBG = 2.5

16% of UBG are on the X

• MBG are under-represented on the X chromosome

  • 11% of MBG are on the X

• while FBG are enriched on the X

  • 21% of FBG are on the X

• X-inactivation (or X suppression): X chromosome becomes transcriptionally inactive in the male germline

  • makes sense for testi expressed genes to not be here

• Sexual conflict: expression of a MBG may have a deleterious effect on females.

  • X spends twice as much time in females as it does in males, the female interests will outweigh the male interests.

    -> reduced expression of X-linked MBG

• Dosage, just 1, and drosophila has no Dosage compensation in male germline

-> selective pressure for MBG to “escape” the X and move to an autosome by retrotransposition

there is an excess of Drosophila retrotransposed genes that have moved from the X to the autosomes. Most of these are expressed in testes.

• males have only 1 copy of the X, while females have 2 copies. Thus, one might expect X-linked genes to have twice as much expression in females as in males.

• However, most species have mechanisms of dosage compensation to equilize expression between the sexes.

• drosophila does not have this in germline

• in many ZW taxa, there does not appear to be Z- chromosome dosage compensation in females, leading to an excess of MBG on the Z

  • (females ZW, males ZZ)

Ka/Ks controls for possible differences in mutation rates.

combining expression data from microarrays and comparative genomic data: use Ka/Ks

• MBG show greater divergence between species than FBG and UBG.

• The biggest difference is at nonsynonymous sites, indicating a faster rate of protein evolution in MBG.

• FBG appear to evolve slightly faster than UBG.

• The strongest difference is seen for genes expressed in reproductive organs

• MBG genes are under less selective constraint.

  ->They can accumulate many neutral amino acid changes that have no effect on fitness.

• MBG are subject to more positive (or sexual) selection.

  -> They accumulate more adaptive amino acid replacements.

if it was under less constraint, MBG should

• have more amino acid polymorphism within species than other genes

• should be proportional to the amount of divergence between species

test this with McDonald-Kreitman (MK) test

• compares the ratio

  • (Dn/Ds) divergence at nonsynonymous and synonymous sites

  • (Pn/Ps) polymorphism at nonsynonymous and synonymous sites

If the ratios are equal (do not differ significantly)

-> neutral evolution

If there is an excess of nonsynonymous divergence

-> positive selection

If there is an excess of nonsynonymous polymorphism

-> balancing selection or weak

purifying selection

For Drosophila MBG, (Dn/Ds)/(Pn/Ps) ≈ 2.

For FBG it is ≈ 1.2

For UBG it is ≈ 0.9

X-linked MBG show a stronger signal of positive selection than autosomal MBG.

For X-linked MBG, (Dn/Ds)/(Pn/Ps) ≈ 3.4.

X-linked MBG also show the highest divergence (measured by Ka/Ks).

Correlation between evolutionary rate and recombination rate

• Selection is more efficient in regions of high recombination, because each mutation can be

  selected independently.

• If changes are due to positive selection, then we see a positive correlation between divergence and recombination rate

  • -> the case for MBG

  • not the case for FBG, UBG (most aa changes in these genes are deleterious and are removed by purifying selection)

Direction of selection

• compares the ratio

  • (Dn/Ds) divergence at nonsynonymous and synonymous sites

  • (Pn/Ps) polymorphism at nonsynonymous and synonymous sites

If the ratios are equal (do not differ significantly)

-> neutral evolution

If there is an excess of nonsynonymous divergence

-> positive selection

If there is an excess of nonsynonymous polymorphism

-> balancing selection or weak purifying selection

• The rate of adaptive evolution is expected to be faster on the X chromosome if beneficial mutations are, on average, recessive.

• Recessive beneficial mutations on the X will be “seen”immediately by selection in males, since males are hemizygous for the X chromosome.

• the effects of beneficial recessive mutations on autosomes will only be “seen” in males or females after the mutation reaches high enough frequency to be homozygous in some individuals.

• This describes the results of studies mapping the loci responsible for hybrid incompatibilities between species (especially hybrid male sterility).

• Such studies found that there is a large excess of incompatible loci on the X chromosome relative to the autosomes.

• Thus, the X appears to play a disproportionately large role in speciation.